metformin and Cardiovascular Diseases studies

Metformin: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289)
metformin : A member of the class of guanidines that is biguanide the carrying two methyl substituents at position 1.

Cardiovascular Diseases: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.

Research Excerpts

Excerpt	Relevance	Reference
"Metformin is widely used in pregnancy, despite lack of long-term safety for children."	9.51	Metformin in obese pregnancy has no adverse effects on cardiovascular risk in early childhood. ( Denison, FC; Dhaun, N; Drake, AJ; Lacey, L; Norman, JE; Quenby, S; Reynolds, RM; Whyte, S; Yang, L, 2022)
"To evaluate the effect of metformin on cardiovascular risk factors in middle-aged Thai women with metabolic syndrome that are in menopausal transition."	9.34	Effect of metformin on cardiovascular risk factors in middle-aged Thai women with metabolic syndrome: A randomized placebo-controlled trial. ( Dangrat, C; Indhavivadhana, S; Jirattigalachote, A; Rattanachaiyanont, M; Techatraisak, K; Wongwananurak, T, 2020)
"This study aimed to evaluate the effects of metformin and conjugated linoleic acid (CLA) on insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp technique and insulin pathway expression molecules in muscle biopsies of children with obesity."	9.24	Effects of Conjugated Linoleic Acid and Metformin on Insulin Sensitivity in Obese Children: Randomized Clinical Trial. ( Alvarez, F; Bustos, M; Cuevas, S; Duggirala, R; Fonseca-Sánchez, M; Garibay-Nieto, N; Jalife, A; Laresgoiti-Servitje, E; León, M; López-Alvarenga, JC; Macías, T; Queipo-García, G; Ramírez, F; Serratos, F; Villanueva, E, 2017)
"Whether metformin reduces all-cause cardiovascular mortality and the incidence of cardiovascular events in patients with pre-existing cardiovascular diseases (CVD) remains inconclusive."	9.22	Association of Metformin with the Mortality and Incidence of Cardiovascular Events in Patients with Pre-existing Cardiovascular Diseases. ( Chang, ACY; Gu, C; Jiang, W; Li, T; Liu, M; Ma, H; Providencia, R; Yu, L, 2022)
"The study included two age-, weight-, lipid-, and prolactin level-matched groups of premenopausal women with hypecholesterolemia and a history of hyperprolactinemia: patients treated with bromocriptine (5."	9.20	The Effect of Atorvastatin on Cardiometabolic Risk Factors in Bromocriptine-Treated Premenopausal Women with Isolated Hypercholesterolemia. ( Gilowski, W; Krysiak, R; Okopien, B; Szkrobka, W, 2015)
"To evaluate the long-term effects of drospirenone (DRSP)/ethinylestradiol (EE) alone, metformin alone, and DRSP/EE-metformin on CD4(+)CD28(null) T lymphocytes frequency, a cardiovascular risk marker, in patients with hyperinsulinemic polycystic ovary syndrome (PCOS)."	9.17	Effects of drospirenone-ethinylestradiol and/or metformin on CD4(+)CD28(null) T lymphocytes frequency in women with hyperinsulinemia having polycystic ovary syndrome: a randomized clinical trial. ( Apa, R; Ciardulli, A; Cosentino, N; Crea, F; Familiari, A; Lanzone, A; Liuzzo, G; Martinez, D; Morciano, A; Moro, F; Niccoli, G; Palla, C; Sagnella, F; Scarinci, E; Tritarelli, A; Tropea, A, 2013)
"In young women with PCOS, treatment with metformin or pioglitazone for 6 months induces a similar beneficial effect on endothelial function; this may be partially attributed to an improvement in insulin resistance."	9.15	Effect of the insulin sensitizers metformin and pioglitazone on endothelial function in young women with polycystic ovary syndrome: a prospective randomized study. ( Bechlioulis, A; Calis, KA; Chrousos, GP; Kalantaridou, SN; Katsouras, CS; Kazakos, N; Kravariti, M; Makrigiannakis, A; Michalis, LK; Naka, KK; Tsatsoulis, A, 2011)
" ADMA, homocysteine, high sensitive C-reactive protein (hs-CRP) and homeostasis model assessment estimate of insulin resistance (HOMA-IR) were investigated."	9.15	Inflammatory-metabolic parameters in obese and nonobese normoandrogenemic polycystic ovary syndrome during metformin and oral contraceptive treatment. ( Aydin, M; Batioglu, S; Erdogan, G; Kilic, S; Yilmaz, N; Zulfikaroglu, E, 2011)
"OBJECTIVE To compare the effect of short-term metformin and fenofibrate treatment, administered alone or in sequence, on glucose and lipid metabolism, cardiovascular risk factors, and monocyte cytokine release in type 2 diabetic patients with mixed dyslipidemia."	9.14	Pleiotropic action of short-term metformin and fenofibrate treatment, combined with lifestyle intervention, in type 2 diabetic patients with mixed dyslipidemia. ( Krysiak, R; Okopien, B; Pruski, M, 2009)
"To study if metformin, when administered to first-degree relatives of type 2 diabetes mellitus subjects who have metabolic syndrome and normal glucose tolerance, could improve the cardiovascular risk profile and reduce the levels of both C-reactive protein and fibrinogen."	9.14	Short-term treatment with metformin improves the cardiovascular risk profile in first-degree relatives of subjects with type 2 diabetes mellitus who have a metabolic syndrome and normal glucose tolerance without changes in C-reactive protein or fibrinogen ( Bouskela, E; Kraemer-Aguiar, LG; Lima, LM; Wiernsperger, N, 2009)
"To evaluate the effects of a pill with drospirenone (3 mg) plus ethinyl E(2) (20 μg) (DRP/20EE) alone or associated with metformin or cyproterone acetate (CPA) on some metabolic cardiovascular risk factors in women with polycystic ovary syndrome (PCOS)."	9.14	Comparison of effects of 3 mg drospirenone plus 20 μg ethinyl estradiol alone or combined with metformin or cyproterone acetate on classic metabolic cardiovascular risk factors in nonobese women with polycystic ovary syndrome. ( Fruzzetti, F; Gambacciani, M; Genazzani, AR; Lazzarini, V; Parrini, D; Perini, D, 2010)
"Blood pressure, body mass, glycemia and blood lipids, hyperinsulinemia, fat mass were studied in 30 patients with diabetes mellitus type 2 and hypertension on metformine treatment in a dose 1500 mg/day."	9.12	[Metabolic and hemodynamic effects of combined treatment with metformine and rosiglitasone (avandium) in patients with diabetes mellitus type 2 and high cardiovascular risk]. ( Demidova, TIu; Erokhina, EN, 2007)
"To investigate the effects of metformin on glycemic control, insulin resistance, and risk factors for cardiovascular disease in NIDDM subjects from two ethnic groups (Caucasian and Asian) with different risks of cardiovascular disease."	9.07	Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. A study of two ethnic groups. ( Nagi, DK; Yudkin, JS, 1993)
"To discussing metformin effects on rheumatoid arthritis complications."	9.01	Metformin one in a Million Efficient Medicines for Rheumatoid Arthritis Complications: Inflammation, Osteoblastogenesis, Cardiovascular Disease, Malignancies. ( Haybar, H; Mowla, K; Rajaei, E; Zayeri, ZD, 2019)
"Metformin is not currently used for weight loss or diabetes prevention because it lacks an FDA indication for obesity and/or pre-diabetes treatment."	8.93	Metformin: an Old Therapy that Deserves a New Indication for the Treatment of Obesity. ( Apovian, CM; Aronne, LJ; Igel, LI; Saunders, KH; Sinha, A; Vojta, D, 2016)
" However, the antihyperglycaemic agent metformin appears promising in some recent studies and we review the literature that evaluates metformin for limiting or reversing atypical antipsychotic drug-induced weight gain and glucose metabolism dysregulation."	8.86	Metformin for atypical antipsychotic-induced weight gain and glucose metabolism dysregulation: review of the literature and clinical suggestions. ( Fredrickson, SK; Hasnain, M; Vieweg, WV, 2010)
" Limited data demonstrated no evidence of a difference in effect between metformin and the OCP on hirsutism, acne or development of type 2 diabetes mellitus."	8.84	Metformin versus oral contraceptive pill in polycystic ovary syndrome: a Cochrane review. ( Costello, MF; Eden, J; Johnson, NP; Shrestha, B; Sjoblom, P, 2007)
"Use of metformin in polycystic ovary syndrome (PCOS) is becoming increasingly accepted and widespread, but clinical practice is ahead of the evidence."	8.82	Descriptive review of the evidence for the use of metformin in polycystic ovary syndrome. ( Fleming, R; Harborne, L; Lyall, H; Norman, J; Sattar, N, 2003)
" In this context, metformin has been shown to not only contribute to a better glycaemic control but also to induce some weight loss (especially in the visceral depot) which may contribute to the improvement of the features of the metabolic syndrome."	8.82	Potential contribution of metformin to the management of cardiovascular disease risk in patients with abdominal obesity, the metabolic syndrome and type 2 diabetes. ( Després, JP, 2003)
" The most extensively studied insulin-lowering agent in the treatment of PCOS is metformin: an oral antihyperglycaemic agent used initially in the treatment of type 2 diabetes mellitus."	8.81	Should patients with polycystic ovarian syndrome be treated with metformin? ( Duleba, AJ; Seli, E, 2002)
"The debate on metformin use in polycystic ovary syndrome (PCOS) has mainly focused on its treatment for infertility in ovulation induction and menstrual cyclicity."	8.81	Should patients with polycystic ovary syndrome be treated with metformin? Benefits of insulin sensitizing drugs in polycystic ovary syndrome--beyond ovulation induction. ( Oehninger, S; Stadtmauer, LA; Wong, BC, 2002)
" This self-controlled case series study aims to evaluate whether metformin use and SGLT2i-associated erythrocytosis influence its cardiovascular benefits."	8.12	Cardiovascular benefits of SGLT2 inhibitors in type 2 diabetes, interaction with metformin and role of erythrocytosis: a self-controlled case series study. ( Au, ICH; Lau, KTK; Lee, CH; Lee, CYY; Lui, DTW; Tan, KCB; Tang, EHM; Wong, CKH; Woo, YC, 2022)
"Of those prescribed metformin, 83% were overweight or obese and 72% had elevated HOMA2-IR scores."	8.12	Metabolic and clinical profiles of young people with mood or psychotic disorders who are prescribed metformin in an inpatient setting. ( Carpenter, J; Hickie, IB; McHugh, C; Park, S; Scott, EM; Wilson, C, 2022)
"To our knowledge, no meta-analyses or reviews have investigated the efficacy and safety of metformin on cardiovascular outcomes after acute myocardial infarction (AMI) in patients with type 2 diabetes mellitus (T2DM)."	8.02	Effects of continuous use of metformin on cardiovascular outcomes in patients with type 2 diabetes after acute myocardial infarction: A protocol for systematic review and meta-analysis. ( Shen, C; Tan, S; Yang, J, 2021)
"In this analysis of electronic health record data from a large database in China, metformin as first-line monotherapy greatly reduced the risk of all-cause death, cardiovascular death, and heart failure in diabetes patients as compared with nonmetformin medications."	8.02	Risk of Death and Heart Failure among Patients with Type 2 Diabetes Treated by Metformin and Nonmetformin Monotherapy: A Real-World Study. ( Chen, X; Chen, Y; He, S; Li, G; Qian, X; Shen, X; Xu, X; Zhang, B, 2021)
" Metformin is commonly used to treat insulin resistance-glucose intolerance, and flutamide, an androgen receptor (AR) antagonist, is used to target hyperandrogenemia and dyslipidemia."	7.91	Effect of metformin and flutamide on insulin, lipogenic and androgen-estrogen signaling, and cardiometabolic risk in a PCOS-prone metabolic syndrome rodent model. ( Diane, A; Ghosh, M; Kupreeva, M; Lehner, R; Proctor, S; Vine, D; Watts, R, 2019)
"There is considerable evidence that metformin reduces weight gain associated with antipsychotic medication."	7.85	Developing a metformin prescribing tool for use in adults with mental illness to reduce medication-related weight gain and cardiovascular risk. ( Galletly, C; Myles, H; Smith, C, 2017)
"The objective of this nationwide study was to compare the risk of all-cause mortality, fatal and nonfatal cardiovascular disease (CVD), and severe hypoglycemia in patients with type 2 diabetes (T2D) on metformin monotherapy treatment starting second-line treatment with either insulin or dipeptidyl peptidase-4 inhibitor (DPP-4i)."	7.85	Second line initiation of insulin compared with DPP-4 inhibitors after metformin monotherapy is associated with increased risk of all-cause mortality, cardiovascular events, and severe hypoglycemia. ( Bodegard, J; Eriksson, JW; Nathanson, D; Norhammar, A; Nyström, T; Thuresson, M, 2017)
"Despite the limitations of this observational study, diabetes patients with MS who were treated with metformin plus DPP-4 inhibitors had better compliance, greater metabolic control, and lower rates of hypoglycemia, causing lower costs for the Spanish national health system than patients receiving metformin plus other antidiabetes drugs."	7.80	Healthcare costs of the combination of metformin/dipeptidyl peptidase-4 inhibitors compared with metformin/other oral antidiabetes agents in patients with type 2 diabetes and metabolic syndrome. ( Navarro-Artieda, R; Sicras-Mainar, A, 2014)
"To examine the safety and potential benefits of metformin in diabetic patients with cardiovascular (CV) disease and heart failure (HF)."	7.79	Evaluating the potential benefits of metformin in patients with cardiovascular disease and heart failure. ( Amin, SM; Chilipko, AA; Macharia, D; Norwood, DK; Still, KL, 2013)
"Serum hsCRP improved with lifestyle modification and metformin therapy for 3 months in overweight subjects from India with PCOS, along with serum total cholesterol, triglycerides, and HDL-C."	7.78	Effect of lifestyle modification and metformin therapy on emerging cardiovascular risk factors in overweight Indian women with polycystic ovary syndrome. ( Bitla, A; P V L N Rao, S; Rajagopal, G; Reddy, AP; Sachan, A; Suresh, V; Venkata Harinarayan, C, 2012)
"We investigated whether the addition of metformin to the treatment of overweight and obese individuals further reduces the incidence of type 2 diabetes mellitus (T (2)DM), prediabetes and metabolic syndrome (MetS) and improves cardiovascular disease (CVD) risk factors (RFs)."	7.75	The effect of metformin on the incidence of type 2 diabetes mellitus and cardiovascular disease risk factors in overweight and obese subjects--the Carmos study. ( Andreadis, EA; Diamantopoulos, EJ; Georgiopoulos, DX; Gouveri, ET; Katsanou, PM; Tsourous, GI; Yfanti, GK, 2009)
"There are conflicting data regarding the effects of metformin in lean women with polycystic ovary syndrome (PCOS)."	7.74	The effects of metformin on metabolic and cardiovascular risk factors in nonobese women with polycystic ovary syndrome. ( Aygen, E; Kelestimur, F; Sahin, Y; Unluhizarci, K; Yikilmaz, A; Yilmazsoy, A, 2007)
"Recent data indicate that women affected by the polycystic ovary syndrome (PCOS) are at greater risk for cardiovascular disease and that metformin may improve the metabolic alterations in these patients."	7.73	Improvement in endothelial structure and function after metformin treatment in young normal-weight women with polycystic ovary syndrome: results of a 6-month study. ( Azziz, R; Cascella, T; Colao, A; De Simone, B; Lombardi, G; Manguso, F; Orio, F; Palomba, S; Russo, T; Savastano, S; Tolino, A; Zullo, F, 2005)
" Obesity is the most important risk factor to develop this disease and metformin is considered as a first line drug in overweighted diabetic patients."	7.73	[Metformin in the treatment of type 2 diabetes in overweighted or obese patients]. ( Costa Zamora, P; Díaz, JM; González Alvaro, A; Martín Muñoz, MC; Muros Bayo, JM, 2005)
"The present study represents a new insight into the Biguanides and the Prevention of the Risk of Obesity (BIGPRO) 1 study population at inclusion."	7.71	Accumulation of triglyceride-rich lipoprotein in subjects with abdominal obesity: the biguanides and the prevention of the risk of obesity (BIGPRO) 1 study. ( André, P; Bard, JM; Charles, MA; Eschwege, E; Fruchart, JC; Juhan-Vague, I; Safar, M; Vague, P, 2001)
"Metformin is a medication likely to improve measures of cardiometabolic disturbance in young people with mental illness."	7.30	Double-blind, randomised placebo-controlled clinical trial of metformin as an adjunct to a sleep-wake, activity and metabolically focused behavioural intervention to improve cardiometabolic outcomes and mood symptoms in youth with major mood syndromes: st ( Carpenter, JS; Crouse, J; Hamilton, B; Hickie, IB; Hockey, S; Koethe, D; McHugh, C; Nichles, A; Scott, EM; Song, YJC; Wilson, C; Zmicerevska, N, 2023)
"Empagliflozin is a sodium-glucose-cotransporter-2 inhibitor that improves cardiovascular risk and promotes weight loss in patients with type-2 diabetes."	6.90	Effects of empagliflozin on metabolic parameters in polycystic ovary syndrome: A randomized controlled study. ( Abbas, J; Atkin, SL; Deshmukh, H; Javed, Z; Khan, AY; Kilpatrick, ES; Papageorgiou, M; Qamar, U; Rigby, AS; Sathyapalan, T, 2019)
"Prediabetes is associated with increased prevalence of cardiovascular disease (CVD)."	6.87	Effect of intensive lifestyle modification & metformin on cardiovascular risk in prediabetes: A pilot randomized control trial. ( Bantwal, G; Fathima, S; George, B; Kulkarni, S; Umesh, S; Xavier, D, 2018)
"Metformin has been in clinical use for the management of type 2 diabetes for more than 60 years and is supported by a vast database of clinical experience: this includes evidence for cardioprotection from randomised trials and real-world studies."	6.82	Metformin and the heart: Update on mechanisms of cardiovascular protection with special reference to comorbid type 2 diabetes and heart failure. ( Bailey, CJ; Brand, K; Schernthaner, G, 2022)
"Atherosclerosis is a common cause of cardiovascular disease, which, in turn, is often fatal."	6.82	From Diabetes to Atherosclerosis: Potential of Metformin for Management of Cardiovascular Disease. ( Litvinova, L; Moschetta, D; Orekhov, AN; Poggio, P; Poznyak, AV; Sukhorukov, VN, 2022)
"Pioglitazone has demonstrated a favorable CV profile relative to other oral antidiabetic drugs (OADs) in outcome and observational studies."	6.75	Effects of pioglitazone and metformin fixed-dose combination therapy on cardiovascular risk markers of inflammation and lipid profile compared with pioglitazone and metformin monotherapy in patients with type 2 diabetes. ( Arora, V; Jacks, R; Perez, A; Spanheimer, R, 2010)
"Simvastatin treatment was superior to metformin alone, whereas a combination of simvastatin and metformin was not significantly superior to simvastatin alone."	6.74	Comparison of simvastatin and metformin in treatment of polycystic ovary syndrome: prospective randomized trial. ( Banaszewska, B; Duleba, AJ; Pawelczyk, L; Spaczynski, RZ, 2009)
"Metformin was well tolerated and no one discontinued treatment due to side effects."	6.70	Sustained benefits of metformin therapy on markers of cardiovascular risk in human immunodeficiency virus-infected patients with fat redistribution and insulin resistance. ( Grinspoon, S; Hadigan, C; Rabe, J, 2002)
"Metformin is a widely used drug in the treatment of type 2 diabetes mellitus (T2DM)."	6.52	Novel therapeutic targets of metformin: metabolic syndrome and cardiovascular disease. ( Bettencourt, N; Fontes-Carvalho, R; Gama, V; Ladeiras-Lopes, R; Leite-Moreira, A; Sampaio, F, 2015)
"Metformin has been introduced as a therapeutic option in PCOS, targeting of cardiometabolic and reproductive abnormalities on the basis of its action on the reduction of glucose levels and the attenuation of insulin resistance."	6.46	Metformin in polycystic ovary syndrome. ( Christakou, C; Diamanti-Kandarakis, E; Economou, F; Palimeri, S, 2010)
"Metformin is an insulin sensitizer widely used for the treatment of patients affected by type 2 diabetes mellitus."	6.45	Evidence-based and potential benefits of metformin in the polycystic ovary syndrome: a comprehensive review. ( Falbo, A; Orio, F; Palomba, S; Zullo, F, 2009)
" They also suggest that long term administration of metformin might be helpful in treating insulin resistance, thus reducing risks of type 2 (non-insulin-dependent) diabetes and cardiovascular disease in these patients."	6.40	Insulin resistance, polycystic ovary syndrome and metformin. ( Ducluzeau, PH; Pugeat, M, 1999)
"<6."	5.56	Metformin Should Not Be Used to Treat Prediabetes. ( Davidson, MB, 2020)
"Oral metformin supplementation once daily for 24 weeks as an adjuvant therapy to intensive insulin in pediatric T1DM was safe and effective in improving glycemic control, dyslipidemia and Nrg-4 levels; hence, it decreased inflammation, microvascular complications and subclinical atherosclerosis."	5.51	Effect of metformin as an add-on therapy on neuregulin-4 levels and vascular-related complications in adolescents with type 1 diabetes: A randomized controlled trial. ( Elbarbary, NS; Ghallab, MA; Ismail, EAR, 2022)
"Although patients with type 2 diabetes mellitus (T2DM) may fail to achieve adequate hemoglobin A1c (HbA1c) control despite metformin-sulfonylurea (Met-SU) dual therapy, a third-line glucose-lowering medication-including dipeptidyl peptidase-4 inhibitor (DPP4i), insulin, or thiazolidinedione (TZD)-can be added to achieve this."	5.51	Intensification with dipeptidyl peptidase-4 inhibitor, insulin, or thiazolidinediones and risks of all-cause mortality, cardiovascular diseases, and severe hypoglycemia in patients on metformin-sulfonylurea dual therapy: A retrospective cohort study. ( Chan, EW; Ho, CW; Lam, CLK; Man, KKC; Shi, M; Tse, ETY; Wong, CKH; Wong, ICK, 2019)
"Metformin is widely used in pregnancy, despite lack of long-term safety for children."	5.51	Metformin in obese pregnancy has no adverse effects on cardiovascular risk in early childhood. ( Denison, FC; Dhaun, N; Drake, AJ; Lacey, L; Norman, JE; Quenby, S; Reynolds, RM; Whyte, S; Yang, L, 2022)
"Men with type 2 diabetes are often characterized by abnormal plasma testosterone levels."	5.43	The effect of testosterone on cardiovascular risk factors in men with type 2 diabetes and late-onset hypogonadism treated with metformin or glimepiride. ( Gilowski, W; Krysiak, R; Okopień, B, 2016)
"Metformin-glinides was most cost-effective in the base-case analysis; Metformin-glinides saved $194 USD for one percentage point of reduction in CVD risk, as compared to Metformin-SU."	5.43	Comparative cost-effectiveness of metformin-based dual therapies associated with risk of cardiovascular diseases among Chinese patients with type 2 diabetes: Evidence from a population-based national cohort in Taiwan. ( Chen, YT; Liu, YM; Ou, HT; Wu, JS, 2016)
"The findings from our analyses substantiate the relevance of treatment with SGLT-2 inhibitors or GLP-1RAs as an add-on to metformin in patients with T2D and a high risk for cardiovascular disease, and furthermore, support the recommendation for SGLT-2 inhibitor treatment in patients with T2D and heart failure or established kidney disease."	5.41	Effects of DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors and sulphonylureas on mortality, cardiovascular and renal outcomes in type 2 diabetes: A network meta-analyses-driven approach. ( Brønden, A; Christensen, MB; Glintborg, D; Hansen, KB; Hansen, TK; Højlund, K; Kofoed-Enevoldsen, A; Kristensen, JK; Madsen, GK; Snorgaard, O; Søndergaard, E; Toft, K, 2023)
"While substantial preclinical and clinical evidence suggests metformin as a potential cardiovascular protectant, large-scale randomized controlled trials are warranted to establish its clinical efficacy in treating patients with atherosclerotic cardiovascular disease and heart failure."	5.41	Cardiovascular Protection by Metformin: Latest Advances in Basic and Clinical Research. ( Li, JZ; Li, YR, 2023)
"Metformin treatment increases serum cartonectin levels in these women and in omental AT explants."	5.39	Metformin increases the novel adipokine cartonectin/CTRP3 in women with polycystic ovary syndrome. ( Adya, R; Amar, O; Chen, J; Hu, J; Lehnert, H; Mattu, HS; Patel, V; Ramanjaneya, M; Randeva, HS; Tan, BK, 2013)
"Metformin is an antihyperglycemic agent commonly used in diabetic patients."	5.37	The nephrologist's role in metformin-induced lactic acidosis. ( Basterrechea, MA; de Arriba, G; Gómez-Navarro, L; Hernández-Sevillano, B; Pérez del Valle, KM; Rodríguez-Palomares, JR; Sánchez-Heras, M; Tallón, S; Torres-Guinea, M, 2011)
"To evaluate the effect of metformin on cardiovascular risk factors in middle-aged Thai women with metabolic syndrome that are in menopausal transition."	5.34	Effect of metformin on cardiovascular risk factors in middle-aged Thai women with metabolic syndrome: A randomized placebo-controlled trial. ( Dangrat, C; Indhavivadhana, S; Jirattigalachote, A; Rattanachaiyanont, M; Techatraisak, K; Wongwananurak, T, 2020)
"All-cause mortality, cardiovascular death, cardiovascular events (death, hospitalization for heart failure, myocardial infarction, stroke or myocardial ischemia), end stage renal disease (ESRD) and the kidney disease composite (ESRD or death) were compared in metformin users and non-users with diabetes and CKD enrolled in the Trial to Reduce Cardiovascular Events with Aranesp (darbepoeitin-alfa) Therapy (TREAT) (NCT00093015)."	5.30	Metformin use and cardiovascular events in patients with type 2 diabetes and chronic kidney disease. ( Burdmann, EA; Charytan, DM; Claggett, B; Cooper, ME; Eckardt, KU; Ivanovich, P; Levey, AS; Lewis, EF; Liu, J; McGill, JB; McMurray, JJV; Parfrey, P; Parving, HH; Pfeffer, MA; Remuzzi, G; Singh, AK; Solomon, SD; Weinrauch, LA, 2019)
"In this randomized, prospective, controlled study, 87 non-obese (18-30 BMI) women of reproductive age (18-39) with polycystic ovary syndrome (PCOS) were assigned to control (n = 17), OC (n = 21), combination (n = 20) and metformin (n = 29) therapy groups."	5.27	The effects of different therapeutic modalities on cardiovascular risk factors in women with polycystıc ovary syndrome: A randomızed controlled study. ( Bodur, S; Dundar, O; Kanat-Pektas, M; Kinci, MF; Tutuncu, L, 2018)
"We analyzed data from the Diabetes Prevention Program (DPP) for 2,476 adults in 1996-1999 with prediabetes randomized to receive treatment with lifestyle modification, metformin, or placebo for 2-3 years and followed through 2014 for T2DM and CVD outcomes."	5.27	Use of a Metabolic Syndrome Severity ( DeBoer, MD; Filipp, SL; Gurka, MJ, 2018)
"This study aimed to evaluate the effects of metformin and conjugated linoleic acid (CLA) on insulin sensitivity, measured via euglycemic-hyperinsulinemic clamp technique and insulin pathway expression molecules in muscle biopsies of children with obesity."	5.24	Effects of Conjugated Linoleic Acid and Metformin on Insulin Sensitivity in Obese Children: Randomized Clinical Trial. ( Alvarez, F; Bustos, M; Cuevas, S; Duggirala, R; Fonseca-Sánchez, M; Garibay-Nieto, N; Jalife, A; Laresgoiti-Servitje, E; León, M; López-Alvarenga, JC; Macías, T; Queipo-García, G; Ramírez, F; Serratos, F; Villanueva, E, 2017)
"Whether metformin reduces all-cause cardiovascular mortality and the incidence of cardiovascular events in patients with pre-existing cardiovascular diseases (CVD) remains inconclusive."	5.22	Association of Metformin with the Mortality and Incidence of Cardiovascular Events in Patients with Pre-existing Cardiovascular Diseases. ( Chang, ACY; Gu, C; Jiang, W; Li, T; Liu, M; Ma, H; Providencia, R; Yu, L, 2022)
"The effects of a 1year period of intensive lifestyle change aimed at achieving 7% weight loss or metformin 850mg twice daily versus placebo on HDL-C were assessed in 3070 participants with impaired glucose tolerance, and on HDL particle concentration (HDL-P) and size in a subgroup of 1645 individuals."	5.22	Change in adiponectin explains most of the change in HDL particles induced by lifestyle intervention but not metformin treatment in the Diabetes Prevention Program. ( Bray, G; Goldberg, RB; Horton, E; Kitabchi, A; Krakoff, J; Marcovina, S; Mather, K; Mele, L; Orchard, T; Perreault, L; Temprosa, M; White, N, 2016)
"The study included two age-, weight-, lipid-, and prolactin level-matched groups of premenopausal women with hypecholesterolemia and a history of hyperprolactinemia: patients treated with bromocriptine (5."	5.20	The Effect of Atorvastatin on Cardiometabolic Risk Factors in Bromocriptine-Treated Premenopausal Women with Isolated Hypercholesterolemia. ( Gilowski, W; Krysiak, R; Okopien, B; Szkrobka, W, 2015)
"High blood glucose level, lipid profile disturbances and plasma homocysteine (Hcy) are important risk factors for cardiovascular diseases in patients with type 2 diabetes."	5.20	Effects of metformin plus gliclazide versus metformin plus glimepiride on cardiovascular risk factors in patients with type 2 diabetes mellitus. ( Abd-Allah, GM; Hassan, MH, 2015)
"To evaluate the long-term effects of drospirenone (DRSP)/ethinylestradiol (EE) alone, metformin alone, and DRSP/EE-metformin on CD4(+)CD28(null) T lymphocytes frequency, a cardiovascular risk marker, in patients with hyperinsulinemic polycystic ovary syndrome (PCOS)."	5.17	Effects of drospirenone-ethinylestradiol and/or metformin on CD4(+)CD28(null) T lymphocytes frequency in women with hyperinsulinemia having polycystic ovary syndrome: a randomized clinical trial. ( Apa, R; Ciardulli, A; Cosentino, N; Crea, F; Familiari, A; Lanzone, A; Liuzzo, G; Martinez, D; Morciano, A; Moro, F; Niccoli, G; Palla, C; Sagnella, F; Scarinci, E; Tritarelli, A; Tropea, A, 2013)
" Metformin is an insulin sensitising agent which is known to improve vascular health outcomes in type 2 diabetes (T2D) and other individuals with insulin resistance."	5.17	Does metformin improve vascular health in children with type 1 diabetes? Protocol for a one year, double blind, randomised, placebo controlled trial. ( Anderson, J; Coppin, B; Couper, J; D'Arcy, B; Gent, R; Olds, T; Peña, AS; Sullivan, T, 2013)
"This analysis included 8,192 overweight patients with type 2 diabetes from the Sibutramine Cardiovascular Outcomes (SCOUT) trial randomized to lifestyle intervention with or without sibutramine for up to 6 years."	5.17	Association of hypoglycemic treatment regimens with cardiovascular outcomes in overweight and obese subjects with type 2 diabetes: a substudy of the SCOUT trial. ( Andersson, C; Caterson, I; Coutinho, W; Finer, N; Ghotbi, AA; James, WP; Køber, L; Sharma, AM; Torp-Pedersen, C; Van Gaal, LF, 2013)
"In young women with PCOS, treatment with metformin or pioglitazone for 6 months induces a similar beneficial effect on endothelial function; this may be partially attributed to an improvement in insulin resistance."	5.15	Effect of the insulin sensitizers metformin and pioglitazone on endothelial function in young women with polycystic ovary syndrome: a prospective randomized study. ( Bechlioulis, A; Calis, KA; Chrousos, GP; Kalantaridou, SN; Katsouras, CS; Kazakos, N; Kravariti, M; Makrigiannakis, A; Michalis, LK; Naka, KK; Tsatsoulis, A, 2011)
" ADMA, homocysteine, high sensitive C-reactive protein (hs-CRP) and homeostasis model assessment estimate of insulin resistance (HOMA-IR) were investigated."	5.15	Inflammatory-metabolic parameters in obese and nonobese normoandrogenemic polycystic ovary syndrome during metformin and oral contraceptive treatment. ( Aydin, M; Batioglu, S; Erdogan, G; Kilic, S; Yilmaz, N; Zulfikaroglu, E, 2011)
"OBJECTIVE To compare the effect of short-term metformin and fenofibrate treatment, administered alone or in sequence, on glucose and lipid metabolism, cardiovascular risk factors, and monocyte cytokine release in type 2 diabetic patients with mixed dyslipidemia."	5.14	Pleiotropic action of short-term metformin and fenofibrate treatment, combined with lifestyle intervention, in type 2 diabetic patients with mixed dyslipidemia. ( Krysiak, R; Okopien, B; Pruski, M, 2009)
"To study if metformin, when administered to first-degree relatives of type 2 diabetes mellitus subjects who have metabolic syndrome and normal glucose tolerance, could improve the cardiovascular risk profile and reduce the levels of both C-reactive protein and fibrinogen."	5.14	Short-term treatment with metformin improves the cardiovascular risk profile in first-degree relatives of subjects with type 2 diabetes mellitus who have a metabolic syndrome and normal glucose tolerance without changes in C-reactive protein or fibrinogen ( Bouskela, E; Kraemer-Aguiar, LG; Lima, LM; Wiernsperger, N, 2009)
"The BIGPRO1 trial was a 1-year multicentre, randomized, double-blind, controlled clinical trial of metformin versus placebo, carried out in the early 1990s, in 457 upper-body obese non-diabetic subjects with no cardiovascular diseases or contraindications to metformin."	5.14	Effects of 1-year treatment with metformin on metabolic and cardiovascular risk factors in non-diabetic upper-body obese subjects with mild glucose anomalies: a post-hoc analysis of the BIGPRO1 trial. ( Baccara-Dinet, M; Charles, MA; Diouf, I; Eschwege, E; Fontbonne, A, 2009)
" The modest weight loss with metformin was maintained."	5.14	10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. ( Brenneman, AT; Brown-Friday, JO; Christophi, CA; Fowler, SE; Goldberg, R; Hamman, RF; Hoffman, HJ; Knowler, WC; Nathan, DM; Venditti, E, 2009)
"To evaluate the effects of a pill with drospirenone (3 mg) plus ethinyl E(2) (20 μg) (DRP/20EE) alone or associated with metformin or cyproterone acetate (CPA) on some metabolic cardiovascular risk factors in women with polycystic ovary syndrome (PCOS)."	5.14	Comparison of effects of 3 mg drospirenone plus 20 μg ethinyl estradiol alone or combined with metformin or cyproterone acetate on classic metabolic cardiovascular risk factors in nonobese women with polycystic ovary syndrome. ( Fruzzetti, F; Gambacciani, M; Genazzani, AR; Lazzarini, V; Parrini, D; Perini, D, 2010)
"As compared with the patients receiving insulin monotherapy, the patients taking metformin alone or in combination showed a more effective recovery of carbohydrate and lipid metabolic disturbances, diminished insulin resistance (IR), lowered blood pressure and albuminuria, reduced diastolic dysfunction, and a smaller cardiovascular risk."	5.14	[Capabilities of hypoglycemic therapy in women with decompensated type 2 diabetes mellitus]. ( Elsukova, OS; Onuchin, SG; Onuchina, EL; Solov'ev, OV, 2010)
"Although metformin (MET) is an insulin sensitizer currently used as an adjunct to the treatment of some of the complications of childhood obesity besides type 2 diabetes mellitus, few studies have comprehensively examined its metabolic and clinical effects in obese children with normal glucose tolerance (NGT)."	5.13	Short-term metabolic and cardiovascular effects of metformin in markedly obese adolescents with normal glucose tolerance. ( Burgert, TS; Caprio, S; Duran, EJ; Dziura, J; Goldberg-Gell, R; Katz, S; Tamborlane, WV; Yeckel, CW, 2008)
"In subjects with impaired glucose tolerance (IGT) who participated in the Indian Diabetes Prevention Programme (IDPP), abnormalities related to body mass index, waist circumference (WC), blood pressure (BP), lipid profile and electrocardiography were analysed (at baseline and third-year follow-up) in control, lifestyle modification (LSM), metformin (MET) and LSM + MET groups."	5.13	Beneficial effects of strategies for primary prevention of diabetes on cardiovascular risk factors: results of the Indian Diabetes Prevention Programme. ( Joshi, VV; Mary, S; Ramachandran, A; Snehalatha, C, 2008)
" Lycopene and berberine are natural plants with a wide range of beneficial effects including protective activities against metabolic disorders such as diabetes and cardiovascular diseases."	5.12	Berberine and lycopene as alternative or add-on therapy to metformin and statins, a review. ( Hedayati, N; Naeini, MB; Oskouei, Z; Tabeshpour, J, 2021)
"A recent meta-analysis raised concern regarding an increased risk of myocardial infarction and death from cardiovascular causes associated with rosiglitazone treatment of type 2 diabetes."	5.12	Rosiglitazone evaluated for cardiovascular outcomes--an interim analysis. ( Beck-Nielsen, H; Gomis, R; Hanefeld, M; Home, PD; Jones, NP; Komajda, M; McMurray, JJ; Pocock, SJ, 2007)
"Blood pressure, body mass, glycemia and blood lipids, hyperinsulinemia, fat mass were studied in 30 patients with diabetes mellitus type 2 and hypertension on metformine treatment in a dose 1500 mg/day."	5.12	[Metabolic and hemodynamic effects of combined treatment with metformine and rosiglitasone (avandium) in patients with diabetes mellitus type 2 and high cardiovascular risk]. ( Demidova, TIu; Erokhina, EN, 2007)
"Hypertension was present in 30% of participants at study entry and then increased in the placebo and metformin groups, although it significantly decreased with intensive lifestyle intervention."	5.11	Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the diabetes prevention program. ( Fowler, S; Goldberg, R; Haffner, S; Marcovina, S; Orchard, T; Ratner, R; Temprosa, M, 2005)
"The BIGuanides and Prevention of Risks in Obesity (BIGPRO1) results suggest that metformin would be a suitable candidate for long-term intervention for the prevention of diabetes but that its use in a trial of primary prevention of cardiovascular diseases requires either a reevaluation of its properties toward the most potentially atherogenic anomalies of the IRS or a better definition of the target population."	5.08	The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. BIGPRO Study Group. ( André, P; Bard, JM; Charles, MA; Cohen, JM; Eschwège, E; Fontbonne, A; Grandmottet, P; Isnard, F; Juhan-Vague, I; Safar, ME; Vague, P, 1996)
"To investigate the effects of metformin on glycemic control, insulin resistance, and risk factors for cardiovascular disease in NIDDM subjects from two ethnic groups (Caucasian and Asian) with different risks of cardiovascular disease."	5.07	Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. A study of two ethnic groups. ( Nagi, DK; Yudkin, JS, 1993)
" Metformin seems to be safe and presents evident positive effects on insulin sensitivity, but long-term and consistent data are still missing to establish its role in the pediatric population and the possible effectiveness of other emergent treatments such as glucagon-like peptide-1 analogues, dipeptidylpeptidase-4 inhibitors, dual inhibitors of SGLT1 and SGLT2 and weight loss drugs."	5.05	Metabolic syndrome in children. ( Chiarelli, F; Samvelyan, S; Tagi, VM, 2020)
"To discussing metformin effects on rheumatoid arthritis complications."	5.01	Metformin one in a Million Efficient Medicines for Rheumatoid Arthritis Complications: Inflammation, Osteoblastogenesis, Cardiovascular Disease, Malignancies. ( Haybar, H; Mowla, K; Rajaei, E; Zayeri, ZD, 2019)
" If the patient does not respond with a weight loss of at least 5% and if the HbA1C values are not normalized, pharmacological management should be initiated with a metformin dose of 500 mg / day, increasing up to 1,500 - 1,700 mg / day, according to tolerance."	4.95	Prediabetes in Colombia: Expert Consensus. ( Calderón, C; Castillo, J; Escobar, ID; López-Jaramillo, P; Melgarejo, E; Parra, GA, 2017)
"Metformin is not currently used for weight loss or diabetes prevention because it lacks an FDA indication for obesity and/or pre-diabetes treatment."	4.93	Metformin: an Old Therapy that Deserves a New Indication for the Treatment of Obesity. ( Apovian, CM; Aronne, LJ; Igel, LI; Saunders, KH; Sinha, A; Vojta, D, 2016)
"7% as monotherapy or in combination with metformin (MET), sulfonylureas (SFU), and/or thiazolidinediones (TZD); with mean weight losses of -1."	4.89	Evolution of exenatide as a diabetes therapeutic. ( Bhavsar, S; Cherrington, A; Mudaliar, S, 2013)
" For metformin, the United Kingdom Prospective Diabetes Study (UKPDS) substudy is convincing for a definite effect in reducing myocardial infarction (MI), but the quantitative extent of that is uncertain."	4.88	Cardiovascular disease and oral agent glucose-lowering therapies in the management of type 2 diabetes. ( Home, P, 2012)
" However, the antihyperglycaemic agent metformin appears promising in some recent studies and we review the literature that evaluates metformin for limiting or reversing atypical antipsychotic drug-induced weight gain and glucose metabolism dysregulation."	4.86	Metformin for atypical antipsychotic-induced weight gain and glucose metabolism dysregulation: review of the literature and clinical suggestions. ( Fredrickson, SK; Hasnain, M; Vieweg, WV, 2010)
" Results showed that (i) polycystic ovary syndrome is a risk factor forT2DM but the magnitude of risk is uncertain, (ii) fasting plasma glucose is an inadequate screening test forT2DM in this population and the oral glucose tolerance test is superior, (iii) the identification of women with PCOS for diabetes screening is constrained by current diagnostic criteria for PCOS; however, women with oligomenorrhoea and those with diagnosed PCOS and obesity or a family history of T2DM are at highest risk, (iv) risk factors for T2DM are improved by weight loss interventions and by metformin."	4.86	Type 2 diabetes and cardiovascular disease in polycystic ovary syndrome: what are the risks and can they be reduced? ( Millward, A; Pinkney, J; Stenhouse, E; Tomlinson, J, 2010)
" The only drug that proved to be effective in reducing cardiovascular events is metformin, which increases AMP-activated protein kinase activity and has a potent cardioprotective effect against ischemia-reperfusion injury."	4.86	[Hypoglycemic therapy in heart disease patients with type 2 diabetes mellitus]. ( Cosmi, D; Cosmi, F, 2010)
" Limited data demonstrated no evidence of a difference in effect between metformin and the OCP on hirsutism, acne or development of type 2 diabetes mellitus."	4.84	Metformin versus oral contraceptive pill in polycystic ovary syndrome: a Cochrane review. ( Costello, MF; Eden, J; Johnson, NP; Shrestha, B; Sjoblom, P, 2007)
"The antidiabetic compound pioglitazone, an activator of the intracellular peroxisome proliferator-activated receptor-gamma, and decreases metabolic and vascular insulin resistance."	4.83	Pioglitazone: an antidiabetic drug with cardiovascular therapeutic effects. ( Forst, T; Pfützner, A; Schneider, CA, 2006)
" These initiatives, together with developments in beta(3)-adrenoceptor agonists, 11 beta-hydroxysteroid dehydrogenase Type 1 inhibitors and modulators of the glucagon-like peptide 1 axis, all of which also potentially enhance insulin sensitivity, are critically evaluated."	4.82	Insulin sensitisation in the treatment of Type 2 diabetes. ( Smith, SA; Tadayyon, M, 2003)
"Use of metformin in polycystic ovary syndrome (PCOS) is becoming increasingly accepted and widespread, but clinical practice is ahead of the evidence."	4.82	Descriptive review of the evidence for the use of metformin in polycystic ovary syndrome. ( Fleming, R; Harborne, L; Lyall, H; Norman, J; Sattar, N, 2003)
" Metformin is a biguanide compound which is antihyperglycaemic, reduces insulin resistance and has cardioprotective effects on lipids, thrombosis and blood flow."	4.82	Beneficial effects of metformin on haemostasis and vascular function in man. ( Grant, PJ, 2003)
" In this context, metformin has been shown to not only contribute to a better glycaemic control but also to induce some weight loss (especially in the visceral depot) which may contribute to the improvement of the features of the metabolic syndrome."	4.82	Potential contribution of metformin to the management of cardiovascular disease risk in patients with abdominal obesity, the metabolic syndrome and type 2 diabetes. ( Després, JP, 2003)
" The most extensively studied insulin-lowering agent in the treatment of PCOS is metformin: an oral antihyperglycaemic agent used initially in the treatment of type 2 diabetes mellitus."	4.81	Should patients with polycystic ovarian syndrome be treated with metformin? ( Duleba, AJ; Seli, E, 2002)
"The debate on metformin use in polycystic ovary syndrome (PCOS) has mainly focused on its treatment for infertility in ovulation induction and menstrual cyclicity."	4.81	Should patients with polycystic ovary syndrome be treated with metformin? Benefits of insulin sensitizing drugs in polycystic ovary syndrome--beyond ovulation induction. ( Oehninger, S; Stadtmauer, LA; Wong, BC, 2002)
"Among 8613 first-line SGLT-2i initiators matched to 17 226 metformin initiators, SGLT-2i initiators had a similar risk for MI/stroke/mortality (HR, 0."	4.12	Cardiovascular Outcomes in Patients Initiating First-Line Treatment of Type 2 Diabetes With Sodium-Glucose Cotransporter-2 Inhibitors Versus Metformin : A Cohort Study. ( Glynn, RJ; Patorno, E; Schneeweiss, S; Shin, H, 2022)
" This self-controlled case series study aims to evaluate whether metformin use and SGLT2i-associated erythrocytosis influence its cardiovascular benefits."	4.12	Cardiovascular benefits of SGLT2 inhibitors in type 2 diabetes, interaction with metformin and role of erythrocytosis: a self-controlled case series study. ( Au, ICH; Lau, KTK; Lee, CH; Lee, CYY; Lui, DTW; Tan, KCB; Tang, EHM; Wong, CKH; Woo, YC, 2022)
"Of those prescribed metformin, 83% were overweight or obese and 72% had elevated HOMA2-IR scores."	4.12	Metabolic and clinical profiles of young people with mood or psychotic disorders who are prescribed metformin in an inpatient setting. ( Carpenter, J; Hickie, IB; McHugh, C; Park, S; Scott, EM; Wilson, C, 2022)
"This study aims to assess the prevalence of atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), chronic kidney disease (CKD), and their combined presence in type 2 diabetes (T2D) patients in primary care for whom the 2019 ADA/EASD consensus update "Management of Hyperglycemia in Type 2 Diabetes" recommends GLP-1 receptor agonists (GLP-1RA) or sodium-glucose cotransporter-2 inhibitors (SGLT-I) as first-line medications after metformin."	4.12	Prevalence of Atherosclerotic Cardiovascular Disease, Heart Failure, and Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus: A Primary Care Research Network-based Study. ( Goderis, G; Mamouris, P; Mathieu, C; Vaes, B; van Craeyveld, E, 2022)
"To our knowledge, no meta-analyses or reviews have investigated the efficacy and safety of metformin on cardiovascular outcomes after acute myocardial infarction (AMI) in patients with type 2 diabetes mellitus (T2DM)."	4.02	Effects of continuous use of metformin on cardiovascular outcomes in patients with type 2 diabetes after acute myocardial infarction: A protocol for systematic review and meta-analysis. ( Shen, C; Tan, S; Yang, J, 2021)
"In this analysis of electronic health record data from a large database in China, metformin as first-line monotherapy greatly reduced the risk of all-cause death, cardiovascular death, and heart failure in diabetes patients as compared with nonmetformin medications."	4.02	Risk of Death and Heart Failure among Patients with Type 2 Diabetes Treated by Metformin and Nonmetformin Monotherapy: A Real-World Study. ( Chen, X; Chen, Y; He, S; Li, G; Qian, X; Shen, X; Xu, X; Zhang, B, 2021)
"In patients with T2DM, SGLT2i as first-line treatment may be associated with decreased events of heart failure hospitalization, acute coronary syndrome, and all-cause mortality, compared with metformin as first-line treatment."	3.96	Sodium-glucose cotransporter 2 inhibitor versus metformin as first-line therapy in patients with type 2 diabetes mellitus: a multi-institution database study. ( Chang, CH; Chen, DY; Chen, SW; Chen, TH; Chu, PH; Li, YR; Lin, YS; Mao, CT; Sun, CC; Wu, M; Wu, VC, 2020)
" Metformin is commonly used to treat insulin resistance-glucose intolerance, and flutamide, an androgen receptor (AR) antagonist, is used to target hyperandrogenemia and dyslipidemia."	3.91	Effect of metformin and flutamide on insulin, lipogenic and androgen-estrogen signaling, and cardiometabolic risk in a PCOS-prone metabolic syndrome rodent model. ( Diane, A; Ghosh, M; Kupreeva, M; Lehner, R; Proctor, S; Vine, D; Watts, R, 2019)
" Initiators of metformin and sulfonylurea monotherapy were matched on high-dimensional propensity score, and Cox proportional hazards models were used to compare the rate of cardiovascular events (myocardial infarction, ischaemic stroke, cardiovascular death, and all-cause mortality) with sulfonylureas vs metformin."	3.91	Sulfonylureas as initial treatment for type 2 diabetes and the risk of adverse cardiovascular events: A population-based cohort study. ( Azoulay, L; Douros, A; Filion, KB; Suissa, S; Yin, H; Yu, OH, 2019)
" Accordingly, O304 reduced fasting plasma glucose levels and homeostasis model assessment of insulin resistance (HOMA-IR) in a proof-of-concept phase IIa clinical trial in type 2 diabetes (T2D) patients on Metformin."	3.88	PAN-AMPK activator O304 improves glucose homeostasis and microvascular perfusion in mice and type 2 diabetes patients. ( Backlund, F; Berggren, E; Bergqvist, I; Dahl, U; Edlund, H; Edlund, T; Ericsson, M; Eriksson, B; Kjellkvist, E; Lidh, E; Lindahl, E; Linde, K; Lundberg, I; Steneberg, P; Straseviciene, J; Westman, J, 2018)
"There is considerable evidence that metformin reduces weight gain associated with antipsychotic medication."	3.85	Developing a metformin prescribing tool for use in adults with mental illness to reduce medication-related weight gain and cardiovascular risk. ( Galletly, C; Myles, H; Smith, C, 2017)
"The objective of this nationwide study was to compare the risk of all-cause mortality, fatal and nonfatal cardiovascular disease (CVD), and severe hypoglycemia in patients with type 2 diabetes (T2D) on metformin monotherapy treatment starting second-line treatment with either insulin or dipeptidyl peptidase-4 inhibitor (DPP-4i)."	3.85	Second line initiation of insulin compared with DPP-4 inhibitors after metformin monotherapy is associated with increased risk of all-cause mortality, cardiovascular events, and severe hypoglycemia. ( Bodegard, J; Eriksson, JW; Nathanson, D; Norhammar, A; Nyström, T; Thuresson, M, 2017)
"To identify distinct temporal likelihoods of age-related comorbidity (ARC) diagnoses: cardiovascular diseases (CVD), cancer, depression, dementia, and frailty-related diseases (FRD) in older men with type 2 diabetes (T2D) but ARC naïve initially, and assess the heterogeneous effects of metformin on ARCs and mortality."	3.85	Differential effects of metformin on age related comorbidities in older men with type 2 diabetes. ( Espinoza, SE; Habib, SL; Jo, B; Lorenzo, C; Wang, CP, 2017)
"Using nationwide administrative Danish registries, we followed all individuals without prior stroke or myocardial infarction who initiated metformin and an IS from 1997 through 2009."	3.81	Metformin in combination with various insulin secretagogues in type 2 diabetes and associated risk of cardiovascular morbidity and mortality--a retrospective nationwide study. ( Andersson, C; Fosbøl, EL; Gislason, G; Køber, L; Mogensen, UM; Scheller, NM; Schramm, TK; Torp-Pedersen, C; Vaag, A, 2015)
" sulfonylureas with metformin after failure of first-line treatment is associated with a decreased risk for major adverse cardiovascular events (myocardial infarction and stroke) and for all-cause mortality."	3.81	The combination of DPP-4 inhibitors versus sulfonylureas with metformin after failure of first-line treatment in the risk for major cardiovascular events and death. ( Azoulay, L; Yin, H; Yu, OH, 2015)
"In intention-to-treat analyses, there was no difference in the risk of any cardiovascular event among the add-on combination treatment groups, but significantly lower risks of acute myocardial infarction were found for the glinides plus metformin treatment group (crude hazard ratio 0."	3.81	Cardiovascular risks associated with second-line oral antidiabetic agents added to metformin in patients with Type 2 diabetes: a nationwide cohort study. ( Chang, CH; Chang, YC; Chen, ST; Chuang, LM; Lai, MS; Lin, JW, 2015)
"56]) compared with sulfonylureas as add-on therapy to metformin but had no effect on risks for myocardial infarction and hospitalization for heart failure."	3.81	Effects on Clinical Outcomes of Adding Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas to Metformin Therapy in Patients With Type 2 Diabetes Mellitus. ( Chao, PW; Chen, TJ; Chen, YT; Chu, H; Kuo, SC; Lee, YJ; Li, SY; Lin, CC; Ou, SM; Shih, CJ; Tarng, DC; Wang, SJ; Yang, CY, 2015)
"Over a 20-year period, patients on dapagliflozin were projected to experience relative reductions in the incidence of myocardial infarction (MI), stroke, CV death, and all-cause death of 13."	3.80	Modeling effects of SGLT-2 inhibitor dapagliflozin treatment versus standard diabetes therapy on cardiovascular and microvascular outcomes. ( Alperin, P; Cohen, M; Dziuba, J; Goswami, D; Grossman, HL; Hardy, E; Iloeje, U; Perlstein, I; Racketa, J, 2014)
"Despite the limitations of this observational study, diabetes patients with MS who were treated with metformin plus DPP-4 inhibitors had better compliance, greater metabolic control, and lower rates of hypoglycemia, causing lower costs for the Spanish national health system than patients receiving metformin plus other antidiabetes drugs."	3.80	Healthcare costs of the combination of metformin/dipeptidyl peptidase-4 inhibitors compared with metformin/other oral antidiabetes agents in patients with type 2 diabetes and metabolic syndrome. ( Navarro-Artieda, R; Sicras-Mainar, A, 2014)
"To examine the safety and potential benefits of metformin in diabetic patients with cardiovascular (CV) disease and heart failure (HF)."	3.79	Evaluating the potential benefits of metformin in patients with cardiovascular disease and heart failure. ( Amin, SM; Chilipko, AA; Macharia, D; Norwood, DK; Still, KL, 2013)
"Serum hsCRP improved with lifestyle modification and metformin therapy for 3 months in overweight subjects from India with PCOS, along with serum total cholesterol, triglycerides, and HDL-C."	3.78	Effect of lifestyle modification and metformin therapy on emerging cardiovascular risk factors in overweight Indian women with polycystic ovary syndrome. ( Bitla, A; P V L N Rao, S; Rajagopal, G; Reddy, AP; Sachan, A; Suresh, V; Venkata Harinarayan, C, 2012)
"Higher risks for death (overall and due to cardiovascular disease) and heart failure were found for rosiglitazone compared to pioglitazone."	3.77	Risk of death and cardiovascular outcomes with thiazolidinediones: a study with the general practice research database and secondary care data. ( Gallagher, AM; Leufkens, HG; Seabroke, S; Smeeth, L; van Staa, TP, 2011)
"We investigated whether the addition of metformin to the treatment of overweight and obese individuals further reduces the incidence of type 2 diabetes mellitus (T (2)DM), prediabetes and metabolic syndrome (MetS) and improves cardiovascular disease (CVD) risk factors (RFs)."	3.75	The effect of metformin on the incidence of type 2 diabetes mellitus and cardiovascular disease risk factors in overweight and obese subjects--the Carmos study. ( Andreadis, EA; Diamantopoulos, EJ; Georgiopoulos, DX; Gouveri, ET; Katsanou, PM; Tsourous, GI; Yfanti, GK, 2009)
" We evaluated serum CRP level, before and after metformin therapy in obese women with polycystic ovarian syndrome (PCOS)."	3.74	C-reactive protein in obese PCOS women and the effect of metformin therapy. ( Velija-Asimi, Z, 2007)
"There are conflicting data regarding the effects of metformin in lean women with polycystic ovary syndrome (PCOS)."	3.74	The effects of metformin on metabolic and cardiovascular risk factors in nonobese women with polycystic ovary syndrome. ( Aygen, E; Kelestimur, F; Sahin, Y; Unluhizarci, K; Yikilmaz, A; Yilmazsoy, A, 2007)
"Recent data indicate that women affected by the polycystic ovary syndrome (PCOS) are at greater risk for cardiovascular disease and that metformin may improve the metabolic alterations in these patients."	3.73	Improvement in endothelial structure and function after metformin treatment in young normal-weight women with polycystic ovary syndrome: results of a 6-month study. ( Azziz, R; Cascella, T; Colao, A; De Simone, B; Lombardi, G; Manguso, F; Orio, F; Palomba, S; Russo, T; Savastano, S; Tolino, A; Zullo, F, 2005)
" Obesity is the most important risk factor to develop this disease and metformin is considered as a first line drug in overweighted diabetic patients."	3.73	[Metformin in the treatment of type 2 diabetes in overweighted or obese patients]. ( Costa Zamora, P; Díaz, JM; González Alvaro, A; Martín Muñoz, MC; Muros Bayo, JM, 2005)
"The present study represents a new insight into the Biguanides and the Prevention of the Risk of Obesity (BIGPRO) 1 study population at inclusion."	3.71	Accumulation of triglyceride-rich lipoprotein in subjects with abdominal obesity: the biguanides and the prevention of the risk of obesity (BIGPRO) 1 study. ( André, P; Bard, JM; Charles, MA; Eschwege, E; Fruchart, JC; Juhan-Vague, I; Safar, M; Vague, P, 2001)
"Metformin is a medication likely to improve measures of cardiometabolic disturbance in young people with mental illness."	3.30	Double-blind, randomised placebo-controlled clinical trial of metformin as an adjunct to a sleep-wake, activity and metabolically focused behavioural intervention to improve cardiometabolic outcomes and mood symptoms in youth with major mood syndromes: st ( Carpenter, JS; Crouse, J; Hamilton, B; Hickie, IB; Hockey, S; Koethe, D; McHugh, C; Nichles, A; Scott, EM; Song, YJC; Wilson, C; Zmicerevska, N, 2023)
"In participants with type 2 diabetes, the incidences of microvascular complications and death were not materially different among the four treatment groups."	3.11	Glycemia Reduction in Type 2 Diabetes - Microvascular and Cardiovascular Outcomes. ( Bebu, I; Burch, HB; Buse, JB; Cherrington, AL; Fortmann, SP; Green, JB; Kahn, SE; Kirkman, MS; Krause-Steinrauf, H; Lachin, JM; Larkin, ME; Nathan, DM; Phillips, LS; Pop-Busui, R; Steffes, M; Tiktin, M; Tripputi, M; Wexler, DJ; Younes, N, 2022)
"Metformin is a biguanide, evolved as one of the most widely used medicines."	3.01	Metformin: new applications for an old drug. ( Daneshvar, S; Gholipour-Khalili, E; Hamzehzadeh, S; Hosseini, MS; Majidazar, R; Naseri, A; Rezazadeh-Gavgani, E; Sanaie, S; Seraji, P; Seyedi-Sahebari, S, 2023)
"Stroke and cardiovascular diseases are major causes of death and disability, especially among diabetic patients."	3.01	Can metformin use reduce the risk of stroke in diabetic patients? A systematic review and meta-analysis. ( Forouzannia, SA; Gholamzadeh, R; Hosseini, M; Jabermoradi, S; Paridari, P; Roshdi Dizaji, S; Vazifekhah, S; Vazirizadeh-Mahabadi, M; Yousefifard, M, 2023)
"While type 2 diabetes mellitus (T2DM) increases the risk of cardiac complications, diabetes treatment choices may increase or decrease the rates of cardiac events."	3.01	Treatment of type 2 diabetes patients with heart conditions. ( Aktas, G; Atak Tel, BM; Balci, B; Tel, R, 2023)
"As the pathophysiologic mechanisms of type 2 diabetes mellitus (T2DM) are discovered, there is a switch from glucocentric to a more comprehensive, patient-centered management."	3.01	The Effects of Cardioprotective Antidiabetic Therapy on Microbiota in Patients with Type 2 Diabetes Mellitus-A Systematic Review. ( Bica, IC; Diaconu, CT; Fierbinteanu Braticevici, C; Pantea Stoian, A; Pietroșel, VA; Salmen, T; Stoica, RA; Suceveanu, AI, 2023)
"Patients with type 2 diabetes often have an elevated plasma level of N-terminal pro B-type as a marker of (sub) clinical cardiovascular disease."	3.01	Metformin and N-terminal pro B-type natriuretic peptide in type 2 diabetes patients, a post-hoc analysis of a randomized controlled trial. ( Kooy, A; Lehert, P; Schalkwijk, CG; Stehouwer, CDA; Top, WMC, 2021)
"Empagliflozin is a sodium-glucose-cotransporter-2 inhibitor that improves cardiovascular risk and promotes weight loss in patients with type-2 diabetes."	2.90	Effects of empagliflozin on metabolic parameters in polycystic ovary syndrome: A randomized controlled study. ( Abbas, J; Atkin, SL; Deshmukh, H; Javed, Z; Khan, AY; Kilpatrick, ES; Papageorgiou, M; Qamar, U; Rigby, AS; Sathyapalan, T, 2019)
"Youth with type 1 diabetes (T1D) carry greater cardiovascular disease (CVD) risk than their nondiabetic peers."	2.90	Serum uromodulin inversely associates with aortic stiffness in youth with type 1 diabetes: A brief report from EMERALD study. ( Baumgartner, A; Bjornstad, P; Coe, G; Cree-Green, M; Johnson, RJ; Nadeau, KJ; Pyle, L; Reyes, YG; Roncal, C; Schäfer, M; Truong, U; Wiromrat, P, 2019)
"TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) was a multicenter randomized trial of 3 treatments including 521 participants with type 2 diabetes, aged 10-17 years, and with 2-6 years of follow-up."	2.87	Cardiac Biomarkers in Youth with Type 2 Diabetes Mellitus: Results from the TODAY Study. ( Bacha, F; Bjornstad, P; El Ghormli, L; Gidding, SS; Levitsky, LL; Levitt Katz, LE; Lima, JAC; Lynch, J; Tryggestad, JB; Weinstock, RS, 2018)
"The primary end point was total cancer incidence."	2.87	Effect of Aspirin on Cancer Chemoprevention in Japanese Patients With Type 2 Diabetes: 10-Year Observational Follow-up of a Randomized Controlled Trial. ( Doi, N; Jinnouchi, H; Masuda, I; Matsumoto, C; Morimoto, T; Nakayama, M; Ogawa, H; Okada, S; Saito, Y; Sakuma, M; Soejima, H; Waki, M, 2018)
"Prediabetes is associated with increased prevalence of cardiovascular disease (CVD)."	2.87	Effect of intensive lifestyle modification & metformin on cardiovascular risk in prediabetes: A pilot randomized control trial. ( Bantwal, G; Fathima, S; George, B; Kulkarni, S; Umesh, S; Xavier, D, 2018)
"Metformin has shown its effectiveness in treating obesity in adults."	2.84	Metformin for Obesity in Prepubertal and Pubertal Children: A Randomized Controlled Trial. ( Aguilera, CM; Bueno, G; Caballero-Villarraso, J; Cañete, MD; Cañete, R; Gil, Á; Hoyos, R; Latorre, M; Leis, R; Maldonado, J; Pastor-Villaescusa, B; Plaza-Díaz, J; Vázquez-Cobela, R, 2017)
"Children with type 1 diabetes have vascular dysfunction preceding atherosclerosis."	2.84	Effect of Metformin on Vascular Function in Children With Type 1 Diabetes: A 12-Month Randomized Controlled Trial. ( Anderson, JJA; Coppin, B; Couper, JJ; Gent, R; Giles, LC; Leggett, CE; Peña, AS, 2017)
" The addition of sitagliptin was generally well tolerated, with a comparable incidence of adverse events and drug-related adverse events in both treatment groups."	2.84	Randomized trial assessing the safety and efficacy of sitagliptin in Chinese patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea alone or combined with metformin. ( Ba, J; Engel, SS; Han, P; Hanson, ME; Mo, Z; Pan, C; Shankar, RR; Wu, F; Xu, L; Yuan, G, 2017)
"Linagliptin has a protective role on endothelial function in patients with type 2 diabetes with moderate hyperglycemia."	2.84	Linagliptin improves endothelial function in patients with type 2 diabetes: A randomized study of linagliptin effectiveness on endothelial function. ( Hirose, T; Iga, R; Kanda, E; Kobayashi, Y; Kumashiro, N; Miyagi, M; Shigiyama, F; Uchino, H, 2017)
" The most common adverse events with exenatide QWS-AI were gastrointestinal events and injection-site reactions."	2.84	Efficacy and safety of autoinjected exenatide once-weekly suspension versus sitagliptin or placebo with metformin in patients with type 2 diabetes: The DURATION-NEO-2 randomized clinical study. ( Gadde, KM; Hardy, E; Iqbal, N; Öhman, P; Vetter, ML, 2017)
" Secondary outcomes were non-cardiovascular adverse events."	2.82	Comparative effectiveness of cardiovascular, renal and safety outcomes of second-line antidiabetic drugs use in people with type 2 diabetes: A systematic review and network meta-analysis of randomised controlled trials. ( Chong, CW; Fong, AYY; Hussein, Z; Khunti, K; Lee, SWH; Loganadan, NK; Navaravong, L; Sim, R, 2022)
"Metformin has been in clinical use for the management of type 2 diabetes for more than 60 years and is supported by a vast database of clinical experience: this includes evidence for cardioprotection from randomised trials and real-world studies."	2.82	Metformin and the heart: Update on mechanisms of cardiovascular protection with special reference to comorbid type 2 diabetes and heart failure. ( Bailey, CJ; Brand, K; Schernthaner, G, 2022)
"Normoglycaemia, prediabetes and type 2 diabetes appear to be part of a continuum of increased risk of adverse outcomes."	2.82	Vascular complications in prediabetes and type 2 diabetes: a continuous process arising from a common pathology. ( Gottwald-Hostalek, U; Gwilt, M, 2022)
"Atherosclerosis is a common cause of cardiovascular disease, which, in turn, is often fatal."	2.82	From Diabetes to Atherosclerosis: Potential of Metformin for Management of Cardiovascular Disease. ( Litvinova, L; Moschetta, D; Orekhov, AN; Poggio, P; Poznyak, AV; Sukhorukov, VN, 2022)
"After run-in on metformin and basal-bolus insulin (BBI), 102 participants continued metformin and basal insulin and were randomized to exenatide dosing before the two largest meals (glucacon-like peptide-1 receptor agonist and insulin [GLIPULIN group]) or continuation of rapid-acting insulin analogs (BBI group)."	2.82	Glucose Variability in a 26-Week Randomized Comparison of Mealtime Treatment With Rapid-Acting Insulin Versus GLP-1 Agonist in Participants With Type 2 Diabetes at High Cardiovascular Risk. ( , 2016)
"Patients with type 2 diabetes failing metformin were randomized to add-on exenatide twice daily (n = 515) or glimepiride (n = 514) until treatment failure defined by hemoglobin A1C."	2.80	Long-term changes in cardiovascular risk markers during administration of exenatide twice daily or glimepiride: results from the European exenatide study. ( Dotta, F; Festa, A; Gallwitz, B; Guerci, B; Kiljański, J; Rosas-Guzmàn, J; Schernthaner, G; Simó, R; Zhou, M, 2015)
" Adverse events (AE) and hypoglycemia were monitored."	2.79	Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus stratified by cardiovascular disease history and cardiovascular risk factors: analysis of 3 clinical trials. ( Bryzinski, B; Cook, W; Hirshberg, B; Minervini, G, 2014)
" Safety was assessed by adverse events, hypoglycemia, and body weight."	2.78	Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus and cardiovascular disease history or cardiovascular risk factors: results of a pooled analysis of phase 3 clinical trials. ( Allen, E; Bryzinski, B; Cook, W; Frederich, R; Slater, J, 2013)
"Women with gestational diabetes mellitus were randomly assigned to metformin or insulin in the Metformin in Gestational Diabetes trial."	2.78	Maternal and neonatal circulating markers of metabolic and cardiovascular risk in the metformin in gestational diabetes (MiG) trial: responses to maternal metformin versus insulin treatment. ( Barrett, HL; Callaway, LK; Coat, S; De Blasio, MJ; Dekker Nitert, M; Gatford, KL; Hague, WM; Houda, CM; McIntyre, HD; Owens, JA; Rowan, JA, 2013)
"Pioglitazone-treated patients were found to have statistically significantly larger decreases in mean CRP levels (-0."	2.78	Effect of pioglitazone versus metformin on cardiovascular risk markers in type 2 diabetes. ( Ceriello, A; De Berardis, G; Evangelista, V; Genovese, S; Mannucci, E; Nicolucci, A; Pellegrini, F; Totani, L, 2013)
"Although weight loss is frequently initiated successfully, most patients regain substantial amounts of weight within the first year after completing a weight loss programme."	2.77	Weight loss/maintenance as an effective tool for controlling type 2 diabetes: novel methodology to sustain weight reduction. ( Gage, D, 2012)
"Metformin is the first-line therapy in type 2 diabetes."	2.77	Addition of either pioglitazone or a sulfonylurea in type 2 diabetic patients inadequately controlled with metformin alone: impact on cardiovascular events. A randomized controlled trial. ( Bonora, E; Del Prato, S; Giorda, CB; Maggioni, AP; Masulli, M; Mocarelli, P; Nicolucci, A; Riccardi, G; Rivellese, AA; Squatrito, S; Vaccaro, O, 2012)
"Metformin was associated with a lower mortality rate (HR 0."	2.76	Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Study. ( Malmberg, K; Mellbin, LG; Norhammar, A; Rydén, L; Wedel, H, 2011)
"Insulin resistance and type 2 diabetes are strongly associated with low grade inflammation."	2.76	The effects of rosiglitazone and metformin on inflammation and endothelial dysfunction in patients with type 2 diabetes mellitus. ( Erem, C; Fidan, E; Karahan, C; Kocak, M; Onder Ersoz, H; Yilmaz, H; Yilmaz, M, 2011)
"Pioglitazone is suggested to be a rational add-on therapy to basal insulin in patients with high CV risk."	2.76	Double-blind, randomized, multicentre, and active comparator controlled investigation of the effect of pioglitazone, metformin, and the combination of both on cardiovascular risk in patients with type 2 diabetes receiving stable basal insulin therapy: the ( Forst, T; Fuchs, W; Hanefeld, M; Kleine, I; Pfützner, A, 2011)
"Metformin-treated patients were likely to be younger, female, or obese."	2.76	Associations between the use of metformin, sulphonylureas, or diet alone and cardiovascular outcomes in 6005 people with type 2 diabetes in the FIELD study. ( Colman, PG; Donoghoe, M; Forder, P; Graham, N; Haapamäki, H; Keech, A; Kritharides, L; Merrifield, A; Simes, J; Sullivan, D; Whiting, M, 2011)
"Pioglitazone has demonstrated a favorable CV profile relative to other oral antidiabetic drugs (OADs) in outcome and observational studies."	2.75	Effects of pioglitazone and metformin fixed-dose combination therapy on cardiovascular risk markers of inflammation and lipid profile compared with pioglitazone and metformin monotherapy in patients with type 2 diabetes. ( Arora, V; Jacks, R; Perez, A; Spanheimer, R, 2010)
"Simvastatin treatment was superior to metformin alone, whereas a combination of simvastatin and metformin was not significantly superior to simvastatin alone."	2.74	Comparison of simvastatin and metformin in treatment of polycystic ovary syndrome: prospective randomized trial. ( Banaszewska, B; Duleba, AJ; Pawelczyk, L; Spaczynski, RZ, 2009)
"A past history of gestational diabetes mellitus (GDM) confers a very high risk of postpartum development of diabetes, particularly type 2 diabetes."	2.73	Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. ( Bennett, PH; Christophi, CA; Dabelea, D; Fowler, S; Kahn, SE; Metzger, BE; Pi-Sunyer, X; Ratner, RE, 2008)
"Five RCTs including 50,725 type 2 diabetes patients, of whom 10,013 had not received metformin, were included in this meta-analysis."	2.72	SGLT2 inhibitors and GLP1 agonists administered without metformin compared to other glucose-lowering drugs in patients with type 2 diabetes mellitus to prevent cardiovascular events: A systematic review. ( Barrios, V; Cosín, J; Escobar, C; Gámez Martínez, JM; Huelmos Rodrigo, AI; Martínez Zapata, MJ; Ortíz Cortés, C; Requeijo, C; Solà, I; Torres Llergo, J, 2021)
" The primary endpoints were all-cause mortality and serious adverse events, and the secondary endpoints were cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, hypoglycemia, and changes in glycated hemoglobin A1c (HbA1c), body weight, fasting plasma glucose, blood pressure, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol."	2.72	Cardiovascular safety and efficacy of metformin-SGLT2i versus metformin-sulfonylureas in type 2 diabetes: systematic review and meta-analysis of randomized controlled trials. ( Gebrie, D; Getnet, D; Manyazewal, T, 2021)
"Metformin is a first-line drug in type 2 diabetes mellitus (T2DM) treatment, yet whether metformin may increase all-cause or cardiovascular mortality of T2DM patients remains inconclusive."	2.72	Association of metformin monotherapy or combined therapy with cardiovascular risks in patients with type 2 diabetes mellitus. ( Chen, M; Gu, C; Li, T; Liu, M; Ma, H; Mu, N; Providencia, R; Wang, Y; Yin, Y; Yu, L, 2021)
"Metformin was associated with a nonsignificant reduction of all-cause mortality (n = 13 RCTs; MH-OR 0."	2.72	Effect of metformin on all-cause mortality and major adverse cardiovascular events: An updated meta-analysis of randomized controlled trials. ( Candido, R; Mannucci, E; Monami, M; Pintaudi, B; Targher, G, 2021)
"Metformin is an established insulin receptor sensitising antihyperglycemic agent, is highly affordable, and has superior safety and efficacy profiles."	2.72	Metformin turns 62 in pharmacotherapy: Emergence of non-glycaemic effects and potential novel therapeutic applications. ( Driver, C; Gcwensa, SK; Mbara, KC; Mcobothi, EN; Mkhombo, NT; Mofo Mato, PE; Nzuza, S; Owira, PM, 2021)
"Semaglutide is an advantageous choice for the treatment of T2D since it has greater efficacy in reducing glycated hemoglobin and body weight compared with other GLP-1RAs, has demonstrated benefits in reducing major adverse cardiovascular events, and has a favorable profile in special populations (e."	2.72	Clinical Perspectives on the Use of Subcutaneous and Oral Formulations of Semaglutide. ( Gallwitz, B; Giorgino, F, 2021)
"Glyburide was associated with a lower risk of cardiovascular events (including congestive heart failure) than was rosiglitazone (P<0."	2.72	Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. ( Haffner, SM; Heise, MA; Herman, WH; Holman, RR; Jones, NP; Kahn, SE; Kravitz, BG; Lachin, JM; O'Neill, MC; Viberti, G; Zinman, B, 2006)
"Thirty-one volunteers with type 2 diabetes mellitus, 16 on dietary therapy and 15 on sulfonylurea monotherapy (SU), were treated with metformin for 12 weeks."	2.71	Effect of metformin treatment on multiple cardiovascular disease risk factors in patients with type 2 diabetes mellitus. ( Abbasi, F; Chu, JW; Lamendola, C; Leary, ET; McLaughlin, T; Reaven, GM, 2004)
"Pioglitazone combination treatment produced significant increases from baseline for average and peak low-density lipoprotein (LDL) particle size at weeks 12 and 24 (p<0."	2.71	Pioglitazone plus a sulphonylurea or metformin is associated with increased lipoprotein particle size in patients with type 2 diabetes. ( Johnson, T; Karunaratne, M; Khan, M; Perez, A, 2004)
"Metformin was well tolerated and no one discontinued treatment due to side effects."	2.70	Sustained benefits of metformin therapy on markers of cardiovascular risk in human immunodeficiency virus-infected patients with fat redistribution and insulin resistance. ( Grinspoon, S; Hadigan, C; Rabe, J, 2002)
"Troglitazone therapy was associated with increases in LDL size (26."	2.70	Differential effects of metformin and troglitazone on cardiovascular risk factors in patients with type 2 diabetes. ( Armstrong, D; Baxi, S; Caulfield, M; Chu, NV; Deutsch, R; Henry, RR; Kim, DD; Kong, AP; Mudaliar, SR; Reaven, PD; Reitz, R, 2002)
"Metformin treatment increases circulating homocysteine levels."	2.69	Folate administration reduces circulating homocysteine levels in NIDDM patients on long-term metformin treatment. ( Aarsand, AK; Carlsen, SM, 1998)
"Metformin was the first glucose-lowering agent reported to improve cardiovascular outcomes in the UK Prospective Diabetes Study (UKPDS) and thus became the foundation of standard care."	2.66	Metformin and cardiorenal outcomes in diabetes: A reappraisal. ( Campbell, IW; Petrie, JR; Rossing, PR, 2020)
"The most characteristic features of type 2 diabetes mellitus (T2DM) are hyperglycaemia and insulin resistance, however, patients with T2DM are at higher risk of cardiovascular disease (CVD) and atherosclerosis."	2.66	An investigation into the pleiotropic activity of metformin. A glimpse of haemostasis. ( Huttunen, KM; Markowicz-Piasecka, M; Mikiciuk-Olasik, E; Podsiedlik, M; Sadkowska, A; Sikora, J, 2020)
"However, statin failed to reduce chronic kidney diseases (CKD) and heart failure (HF)."	2.66	Second revolution in cardiovascular prevention. ( Chao, TF; Cheng, HM; Chiang, CE; Sung, SH; Wang, KL, 2020)
"Preventing prostate cancer via dietary supplements should encourage a "first do no harm" or less-is-more approach until future evidence can reverse the concerning trend that more supplementation has resulted in either no impact or an increased risk of prostate cancer."	2.66	Preventing Lethal Prostate Cancer with Diet, Supplements, and Rx: Heart Healthy Continues to Be Prostate Healthy and "First Do No Harm" Part III. ( Moyad, MA, 2020)
"In the case of patients with type 2 diabetes mellitus and vascular disease or high vascular disease risk, when lifestyle changes and metformin are inadequate, the use of drugs with proven vascular benefit should be prioritised."	2.66	[Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Cardiovascular Prevention Guidelines.] ( Alonso de Leciñana, M; Armario, P; Aznar Lain, S; Brotons, C; Castro, A; Clarà, A; Cortés, O; Díaz Rodriguez, Á; Elosua, R; Herranz, M; Justo, S; Lahoz, C; Pedro-Botet, J; Pérez Pérez, A; Royo-Bordonada, MÁ; Santamaria, R; Tresserras, R, 2020)
"Metformin-based treatments relative to any other measure displayed significantly lower risks of all-cause mortality (Pooled RRs 0."	2.66	Metformin Use and Risk of All-Cause Mortality and Cardiovascular Events in Patients With Chronic Kidney Disease-A Systematic Review and Meta-Analysis. ( Fu, P; Hu, Y; Huang, X; Ke, G; Lei, M; Peng, X; Zhong, L, 2020)
"Type 2 diabetes mellitus is a major risk factor for developing cardiovascular disease, and many patients with diabetes have prevalent cardiovascular complications."	2.61	Glucose-lowering therapies in patients with type 2 diabetes and cardiovascular diseases. ( Ceriello, A; Ferrini, M; La Sala, L; Marx, N; Prattichizzo, F; Rydén, L; Valensi, P, 2019)
"It is thought that it exerts its anti-cancer effect through the inhibition of the mammalian target of rapamycin (mTOR) signalling pathway."	2.61	The journey of metformin from glycaemic control to mTOR inhibition and the suppression of tumour growth. ( Amin, S; Lux, A; O'Callaghan, F, 2019)
"The global epidemic of type 2 diabetes has prompted numerous studies and public health efforts to reduce its development."	2.61	Does diabetes prevention translate into reduced long-term vascular complications of diabetes? ( Bennett, PH; Crandall, JP; Edelstein, SL; Goldberg, RB; Kahn, SE; Knowler, WC; Mather, KJ; Mudaliar, S; Nathan, DM; Orchard, TJ; Temprosa, M; White, NH, 2019)
"Metformin is a biguanide that is widely used as an insulin-sparing agent to treat diabetes."	2.58	Cardioprotection by Metformin: Beneficial Effects Beyond Glucose Reduction. ( Bourji, M; Nader, ND; Pourafkari, L; Varjabedian, L, 2018)
"Metformin has further been reported to restore depleted PGC-1α levels and improve mitochondrial biogenesis by increasing phosphorylation of eNOSser1177, which produces NO and leads to reduced vascular inflammation and myocardial injury after ischemia."	2.58	Cardioprotective Effects of Metformin. ( Bamitale, KDS; Driver, C; Kazi, A; Nyane, NA; Olla, M; Owira, PMO, 2018)
"Cardiovascular diseases are the most prominent maladies in aging societies."	2.58	Autophagy in Cardiovascular Aging. ( Abdellatif, M; Carmona-Gutierrez, D; Kroemer, G; Madeo, F; Sedej, S, 2018)
"Preventing prostate cancer via dietary supplements should encourage a "first do no harm", or less is more approach until future evidence can reverse the concerning trend that more supplementation has resulted in either no impact or an increased risk of prostate cancer."	2.58	Preventing Lethal Prostate Cancer with Diet, Supplements, and Rx: Heart Healthy Continues to Be Prostate Healthy and "First Do No Harm" Part I. ( Moyad, MA, 2018)
"Patients with type 2 diabetes (T2DM) have a significantly higher risk of developing cardiovascular disease (CVD)-namely myocardial infarction, heart failure, and stroke."	2.55	Cardiovascular Protection in the Treatment of Type 2 Diabetes: A Review of Clinical Trial Results Across Drug Classes. ( Lüscher, TF; Paneni, F, 2017)
"Statins have a primary role in the treatment of dyslipidemia in people with type 2 diabetes, defined as triglyceride levels >200 mg/dl and HDL cholesterol levels <40 mg/dL."	2.55	Pharmacologic Treatment of Dyslipidemia in Diabetes: A Case for Therapies in Addition to Statins. ( Anabtawi, A; Miles, JM; Moriarty, PM, 2017)
"Patients with type 2 diabetes (T2DM) have a significantly higher risk of developing cardiovascular disease (CVD)-namely myocardial infarction, heart failure, and stroke."	2.55	Cardiovascular Protection in the Treatment of Type 2 Diabetes: A Review of Clinical Trial Results Across Drug Classes. ( Lüscher, TF; Paneni, F, 2017)
"Choices for the treatment of type 2 diabetes mellitus (T2DM) have multiplied as our understanding of the underlying pathophysiologic defects has evolved."	2.55	Pharmacologic Management of Type 2 Diabetes Mellitus: Available Therapies. ( Thrasher, J, 2017)
"Metformin users also had reduced cancer compared to non-diabetics (rate ratio=0."	2.55	Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis. ( Bellman, SM; Campbell, JM; Lisy, K; Stephenson, MD, 2017)
"The increased risk of type 2 diabetes and cardiovascular disease in PCOS is closely associated with BMI."	2.55	Medical comorbidity in polycystic ovary syndrome with special focus on cardiometabolic, autoimmune, hepatic and cancer diseases: an updated review. ( Andersen, M; Glintborg, D, 2017)
"Metformin has been widely used for over 5 decades."	2.55	Metformin: New Preparations and Nonglycemic Benefits. ( Fujita, Y; Inagaki, N, 2017)
"Empagliflozin is a sodium glucose co-transporter 2 inhibitor used to improve glycemic control in adults with type 2 diabetes mellitus (T2DM) by enhancing urinary glucose excretion."	2.53	A Safety Evaluation of Empagliflozin for the Treatment of Type 2 Diabetes. ( McGuire, DK; Neeland, IJ; Salahuddin, U, 2016)
"Polycystic ovary syndrome is characterized by an excess in androgen levels, ovarian dysfunction, and polycystic ovarian morphology but is also associated with metabolic dysfunction and risk factors for cardiovascular disease."	2.53	Treatment Considerations for the Cardiometabolic Signs of Polycystic Ovary Syndrome: A Review of the Literature Since the 2013 Endocrine Society Clinical Practice Guidelines. ( Fields, EL; Trent, ME, 2016)
"Iatrogenic and compensatory hyperinsulinemia are metabolic disruptors of β-cells, liver, muscle, kidney, brain, heart and vasculature, inflammation, and lipid homeostasis, among other systems."	2.53	Obviating much of the need for insulin therapy in type 2 diabetes mellitus: A re-assessment of insulin therapy's safety profile. ( Herman, ME; Jellinger, PS; Schwartz, SS, 2016)
"Metformin was associated with lower or no significant difference in HbA1C levels compared with any other drug classes."	2.53	Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis. ( Ahmad, N; Badve, SV; Burke, M; Cho, Y; Craig, JC; De Berardis, G; Faruque, L; Gray, V; Johnson, DW; Liu, Y; Lloyd, A; Maggo, J; Mavridis, D; Nadeau-Fredette, AC; Natale, P; Nicolucci, A; Palmer, SC; Ruospo, M; Saglimbene, V; Strippoli, GF; Tiv, S; Tonelli, M; Wiebe, N, 2016)
"Metformin has a dominant position in the treatment of type 2 diabetes that is deserved due to its favorable and robust effects on cardiovascular risk."	2.53	METFORMIN: NONGLYCEMIC EFFECTS AND POTENTIAL NOVEL INDICATIONS. ( Anabtawi, A; Miles, JM, 2016)
"The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into a substantial health problem worldwide."	2.53	Insulin secretagogues for prevention or delay of type 2 diabetes mellitus and its associated complications in persons at increased risk for the development of type 2 diabetes mellitus. ( Hemmingsen, B; Metzendorf, MI; Richter, B; Sonne, DP, 2016)
"Patients with schizophrenia have increased prevalence rates for many cardiometabolic risk factors; the prevalence and severity of these risks increase after the institution of antipsychotic medication."	2.53	Cardiometabolic Risks in Schizophrenia and Directions for Intervention, 3: Psychopharmacological Interventions. ( Andrade, C, 2016)
"Metformin is a widely used drug in the treatment of type 2 diabetes mellitus (T2DM)."	2.52	Novel therapeutic targets of metformin: metabolic syndrome and cardiovascular disease. ( Bettencourt, N; Fontes-Carvalho, R; Gama, V; Ladeiras-Lopes, R; Leite-Moreira, A; Sampaio, F, 2015)
"Insulin resistance is prevalent in women with polycystic ovary syndrome (PCOS), and plays a critical pathophysiologic role in both the metabolic and reproductive complications of PCOS."	2.52	Polycystic ovary syndrome and insulin: our understanding in the past, present and future. ( Evans, WS; Mayer, SB; Nestler, JE, 2015)
"Type 2 diabetes is not only an independent risk factor for cardiovascular (CV) disease but is also associated with a greater incidence of heart failure (HF)."	2.52	Oral hypoglycemic agents and the heart failure conundrum: Lessons from and for outcome trials. ( Federici, M; Kappel, BA; Marx, N, 2015)
"Antidiabetic drugs for type 2 diabetes receive marketing authorization if they show efficacy in reducing levels of HbA(1c)."	2.50	Effects of pharmacological treatments on micro- and macrovascular complications of type 2 diabetes: what is the level of evidence? ( Boussageon, R; Cornu, C; Gueyffier, F, 2014)
"The paper gives an update on type 2 diabetes mellitus concurrent with thyroid dysfunction and on the development of vascular events, atherogenesis and evaluates the impact of therapy on the course of both diseases."	2.50	[Thyroid dysfunction in patients with type 2 diabetes mellitus]. ( Suslina, AA; Tereshchenko, IV, 2014)
"Worldwide, >366 million people with type 2 diabetes mellitus remain at excess risk of cardiovascular disease and face a lifetime of treatment escalation for this progressive disorder."	2.49	Type 2 diabetes mellitus in 2012: Optimal management of T2DM remains elusive. ( Holman, RR, 2013)
" Compliance with the standard metformin formulation can be poor, due to multiple daily dosing and frequent GI side effects."	2.48	Overview of metformin: special focus on metformin extended release. ( Ali, S; Fonseca, V, 2012)
"The metabolic syndrome affects 30% of the US population with increasing prevalence."	2.48	The metabolic syndrome, oxidative stress, environment, and cardiovascular disease: the great exploration. ( Hutcheson, R; Rocic, P, 2012)
"Over 2."	2.48	Targeting the consequences of the metabolic syndrome in the Diabetes Prevention Program. ( Goldberg, RB; Mather, K, 2012)
"The prevalence of type 2 diabetes continues to increase at an alarming rate around the world, with even more people being affected by prediabetes."	2.47	Management of type 2 diabetes: evolving strategies for the treatment of patients with type 2 diabetes. ( Jerkins, TW; Kitabchi, AE; Nyenwe, EA; Umpierrez, GE, 2011)
"Patients with type 2 diabetes often have multiple cardiovascular risk factors and require multiple cardiac and diabetes medications."	2.47	Clinical practice and implications of recent diabetes trials. ( Webster, MW, 2011)
"Successful care of the patient with type 2 diabetes requires not only focus on glucose management but also on comorbidities such as hypertension, dyslipidemia and obesity which are closely linked to microvascular and macrovascular complications."	2.47	Recent diabetes issues affecting the primary care clinician. ( Barboza, J; Sando, KR; Taylor, J; Willis, C, 2011)
"Insulin resistance is linked to polycystic ovary syndrome."	2.47	Current perspectives of insulin resistance and polycystic ovary syndrome. ( Legro, RS; Pauli, JM; Raja-Khan, N; Wu, X, 2011)
"Cardiovascular events occurring in type 2 diabetes (T2DM) are a major problem in clinical practice."	2.46	The cardiovascular effects of metformin: further reasons to consider an old drug as a cornerstone in the therapy of type 2 diabetes mellitus. ( Anfossi, G; Bonomo, K; Russo, I; Trovati, M, 2010)
"Metformin has been introduced as a therapeutic option in PCOS, targeting of cardiometabolic and reproductive abnormalities on the basis of its action on the reduction of glucose levels and the attenuation of insulin resistance."	2.46	Metformin in polycystic ovary syndrome. ( Christakou, C; Diamanti-Kandarakis, E; Economou, F; Palimeri, S, 2010)
"Metformin has shown some benefit in reducing VAT but at the expense of accelerating peripheral fat loss, and the thiazolidinediones have no effect on VAT."	2.45	Treatment options for HIV-associated central fat accumulation. ( Cofrancesco, J; Freedland, E; McComsey, G, 2009)
"Metformin is an insulin sensitizer widely used for the treatment of patients affected by type 2 diabetes mellitus."	2.45	Evidence-based and potential benefits of metformin in the polycystic ovary syndrome: a comprehensive review. ( Falbo, A; Orio, F; Palomba, S; Zullo, F, 2009)
"Metformin is an insulin-sensitizing agent that may lower androgen levels."	2.45	The effects of metformin on endogenous androgens and SHBG in women: a systematic review and meta-analysis. ( Akl, EA; Barba, M; Guyatt, G; Musicco, F; Muti, P; Schünemann, HJ; Sperati, F, 2009)
"Metabolic syndrome is prevalent in older adults and increases the risk of cardiovascular disease."	2.45	Metabolic risks in older adults receiving second-generation antipsychotic medication. ( Brooks, JO; Chang, HS; Krasnykh, O, 2009)
"Metformin has so far consistently succeeded in reducing cardiovascular morbidity and mortality and exerting beneficial effects on lipids."	2.45	Oral antidiabetic agents: anti-atherosclerotic properties beyond glucose lowering? ( Maltezos, E; Papanas, N, 2009)
"Metformin was less effective than the OCP in improving menstrual pattern (Peto odds ratio (OR) 0."	2.44	Insulin-sensitising drugs versus the combined oral contraceptive pill for hirsutism, acne and risk of diabetes, cardiovascular disease, and endometrial cancer in polycystic ovary syndrome. ( Costello, M; Eden, J; Johnson, N; Shrestha, B; Sjoblom, P, 2007)
" Acarbose has a very good safety profile and, owing to its straightforward, non-systemic mode of action, avoids most adverse events."	2.44	Cardiovascular benefits and safety profile of acarbose therapy in prediabetes and established type 2 diabetes. ( Hanefeld, M, 2007)
"Polycystic ovarian syndrome is the commonest endocrine disorder of reproductive-age women."	2.44	Polycystic ovarian syndrome--prognosis and treatment outcomes. ( Hart, R, 2007)
"Obesity is not necessary to observe insulin resistance in humans since severe insulin resistance also characterizes patients lacking subcutaneous fat such as those with HAART (highly-active antiretroviral therapy) - associated lipodystrophy."	2.43	The fatty liver and insulin resistance. ( Westerbacka, J; Yki-Järvinen, H, 2005)
"The primary aim must be the treatment of the insulin resistance."	2.43	[Controversial therapeutic strategies in the treatment of type 2 diabetes mellitus]. ( Schumm-Draeger, PM, 2005)
"Although insulin resistance is not part of the diagnostic criteria for PCOS, its importance in the pathogenesis of PCOS can not be denied."	2.43	Insulin resistance in polycystic ovarian disease. ( Bhatia, V, 2005)
"Prediabetes is important to recognise because of at least 2 major implications: increased risk for future diabetes and for atherosclerotic cardiovascular diseases."	2.43	Drug therapy in prediabetes. ( Chowdhury, S; Mukhopadhyay, P, 2005)
" Evidence for the long-term use of metformin to protect against adverse cardiovascular outcomes and for the use of metformin throughout pregnancy to reduce the risk of miscarriage, gestational diabetes, pre-eclampsia and fetal macrosomia is still lacking."	2.43	Polycystic ovarian syndrome--prognosis and outcomes. ( Hart, R; Norman, R, 2006)
" Pioglitazone and metformin are well tolerated in combination, with low rates of hypoglycemia, and the convenience of a single tablet may be expected to aid dosing compliance."	2.43	A fixed-dose combination of pioglitazone and metformin: A promising alternative in metabolic control. ( Seufert, J, 2006)
"Insulin resistance is now considered to be major pathogenesis for diabetic macroangiopathy."	2.43	[Prevention and treatment for development and progression of diabetic macroangiopathy with pioglitazone and metformin]. ( Daita, H; Mokuno, H; Tamura, H, 2006)
"Patients with type 2 diabetes mellitus are associated with insulin resistance and/or impaired insulin secretion."	2.42	[Nateglinide and mitiglinide]. ( Odawara, M, 2003)
"The predicted global epidemic of type 2 diabetes highlights the importance of identifying the most effective ways to reduce the risk of long-term diabetic complications."	2.42	Metformin and vascular protection: a cardiologist's view. ( Libby, P, 2003)
"Patients with type 2 diabetes have an increased risk for cardiovascular disease (CVD) and it accounts for up to 80% of excess deaths in these patients."	2.42	Role of oral anti-diabetic agents in modifying cardiovascular risk factors. ( Farag, A; McFarlane, SI; Rothman, J; Shin, JJ; Sowers, JR, 2003)
"Treatment with metformin was less effective than lifestyle modifications, resulting in an average reduction of risk of T2D of 31% compared with placebo."	2.41	Can reducing peaks prevent type 2 diabetes: implication from recent diabetes prevention trials. ( Haffner, SM, 2002)
"The characteristic dyslipidemia of insulin resistance consists of elevated triglyceride and triglyceride-rich lipoprotein levels, low levels of high-density lipoprotein cholesterol, and increased concentrations of small, dense low-density lipoprotein cholesterol."	2.41	Pathophysiology and treatment of the dyslipidemia of insulin resistance. ( Capuzzi , DM; Cohn, G; Valdes, G, 2001)
"Metformin is an insulin-sensitizing agent with potent antihyperglycemic properties."	2.41	Metformin: an update. ( Kirpichnikov, D; McFarlane, SI; Sowers, JR, 2002)
" They also suggest that long term administration of metformin might be helpful in treating insulin resistance, thus reducing risks of type 2 (non-insulin-dependent) diabetes and cardiovascular disease in these patients."	2.40	Insulin resistance, polycystic ovary syndrome and metformin. ( Ducluzeau, PH; Pugeat, M, 1999)
"Cardiovascular diseases are characterized by problems affecting the circulatory system, specifically the heart and blood vessels."	1.91	Diabetes mellitus: relation between cardiovascular events and pharmacological treatment. ( Brito-Costa, S; Margalho, L; Monteiro, P; Santos, C, 2023)
"Metformin, a medication for type 2 diabetes, has been linked to many non-diabetes health benefits including increasing healthy lifespan."	1.91	Comparison of long-term effects of metformin on longevity between people with type 2 diabetes and matched non-diabetic controls. ( Escott-Price, V; Leonenko, G; Stevenson-Hoare, J, 2023)
"Metformin was administered to T1DM subjects for eight weeks."	1.91	Decoding of miR-7-5p in Colony Forming Unit-Hill Colonies as a Biomarker of Subclinical Cardiovascular Disease-A MERIT Study. ( Bakhashab, S; Mahaputra, DK; Megantara, HP; O'Neill, J; Phowira, J; Weaver, JU, 2023)
"Depression is one of the most common comorbidities of type 2 diabetes."	1.72	Depression and the risk of hospitalization in type 2 diabetes patients: A nested case-control study accounting for non-persistence to antidiabetic treatment. ( Demers, É; Guénette, L; Lunghi, C; Tardif, I; Zongo, A, 2022)
"Metformin monotherapy was the first-line therapy in 56."	1.72	Prevalence and risk factors of vascular complications in type 2 diabetes mellitus: Results from discover Middle East and Africa cohort. ( Al-Rubeaan, K; Bayram, F; Echtay, A; Hadaoui, A; Hafidh, K; Kok, A; Malek, R; Rajadhyaksha, V, 2022)
"Left ventricular hypertrophy is a common finding in patients with ischemic heart disease and is associated with mortality in patients with cardiovascular disease (CVD)."	1.72	Effect of metformin on left ventricular mass and functional parameters in non-diabetic patients: a meta-analysis of randomized clinical trials. ( Farid, S; Kamel, AM; Sabry, N, 2022)
"Weight loss was 0."	1.72	A Health Care Professional Delivered Low Carbohydrate Diet Program Reduces Body Weight, Haemoglobin A1c, Diabetes Medication Use and Cardiovascular Risk Markers-A Single-Arm Intervention Analysis. ( Brinkworth, GD; Taylor, PJ; Thompson, CH; Wycherley, TP, 2022)
"Metformin was the most common treatment in all patient groups."	1.72	Mode of treatments and achievement of treatment targets among type 2 diabetes patients with different comorbidities - a register-based retrospective cohort study in Finland. ( Laatikainen, T; Lamidi, ML; Lindström, J; Nazu, NA; Rautiainen, P; Tirkkonen, H; Wikström, K, 2022)
"Metformin has been recommended as a first-line antidiabetic drug (ADD) for all patients with type 2 diabetes even in the presence of high cardiovascular (CV) risk by American Diabetes Association."	1.62	Does background metformin therapy influence the cardiovascular outcomes with SGLT-2 inhibitors in type 2 diabetes? ( Singh, AK; Singh, R, 2021)
"Metformin was the most common treatment (>70% of those with and without CVD had prescriptions across all treatment lines)."	1.62	Prescribing in Type 2 Diabetes Patients With and Without Cardiovascular Disease History: A Descriptive Analysis in the UK CPRD. ( Beard, I; Farmer, RE; Gollop, ND; Kanumilli, N; McGovern, AP; Patel, N; Raza, SI; Tebboth, A; Ternouth, A, 2021)
"In the treatment of type 2 diabetes, evidence of the comparative effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors vs sulfonylureas-the second most widely used antihyperglycemic class after metformin-is lacking."	1.62	Comparative Effectiveness of Sodium-Glucose Cotransporter 2 Inhibitors vs Sulfonylureas in Patients With Type 2 Diabetes. ( Al-Aly, Z; Bowe, B; Gibson, AK; Maddukuri, G; McGill, JB; Xie, Y, 2021)
"Clinical trials investigating cardiovascular safety of dipeptidyl peptidase-IV inhibitors (DPP-4i) among patients with cardiovascular and renal disease rarely recruit patients with renal impairment, despite associations with increased risk for major adverse cardiovascular events (MACE)."	1.62	Dipeptidyl peptidase-4 inhibitor cardiovascular safety in patients with type 2 diabetes, with cardiovascular and renal disease: a retrospective cohort study. ( Alexander, GC; Baksh, S; Chang, HY; Ehrhardt, S; Mansour, O; McAdams-DeMarco, M; Segal, JB; Wen, J, 2021)
"Methods and Results Among adults with type 2 diabetes mellitus not controlled with metformin with no prior use of insulin, we assessed for sex differences in the cardiovascular effectiveness and safety of sodium-glucose-like transport-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors, initiated as second-line agents relative to sulfonylureas (reference-group)."	1.56	Sex Differences in Cardiovascular Effectiveness of Newer Glucose-Lowering Drugs Added to Metformin in Type 2 Diabetes Mellitus. ( Abrahamowicz, M; Behlouli, H; Bernatsky, S; Elharram, M; Moura, CS; Pilote, L; Raparelli, V, 2020)
"Metformin use was associated with lower risk for all-cause mortality (hazard ratio [HR], 0."	1.56	A Safety Comparison of Metformin vs Sulfonylurea Initiation in Patients With Type 2 Diabetes and Chronic Kidney Disease: A Retrospective Cohort Study. ( Clemens, KK; Hougen, I; Komenda, P; Rigatto, C; Tangri, N; Whitlock, RH, 2020)
"The effects of type 2 diabetes mellitus (T2DM) medications on secondary prevention after acute coronary syndrome (ACS) remain unclear."	1.56	Recurrent cardiovascular events in patients with newly diagnosed acute coronary syndrome: Influence of diabetes and its management with medication. ( Asano, T; Komaru, Y; Suzuki, L; Takeuchi, T; Urayama, KY, 2020)
"Unhealthy dietary habits contribute to the increasing incidence of metabolic syndrome and type 2 diabetes (T2D), which is accompanied by oxidative stress, compromised nitric oxide (NO) bioavailability and increased cardiovascular risk."	1.56	Head-to-head comparison of inorganic nitrate and metformin in a mouse model of cardiometabolic disease. ( Andersson, DC; Carlström, M; Cordero-Herrera, I; Guimarães, DD; Han, H; Lundberg, JO; McCann Haworth, S; Moretti, C; Uribe Gonzalez, AE; Weitzberg, E; Zhuge, Z, 2020)
"A total of 66,807 people with type 2 diabetes were treated with metformin (MET) plus a combination of second- and third-line therapies."	1.56	Risk of Major Adverse Cardiovascular Events, Severe Hypoglycemia, and All-Cause Mortality for Widely Used Antihyperglycemic Dual and Triple Therapies for Type 2 Diabetes Management: A Cohort Study of All Danish Users. ( Hejlesen, O; Jakobsen, PE; Jensen, MH; Kjolby, M; Vestergaard, P, 2020)
" We aimed to compare the risk of major cardiovascular and adverse events in new users of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), dipeptidyl peptidase-4 inhibitor (DPP-4i), glucagon-like peptide 1 agonist (GLP-1a), and sulfonylurea in T2DM patients not controlled on metformin therapy."	1.56	Novel glucose lowering agents are associated with a lower risk of cardiovascular and adverse events in type 2 diabetes: A population based analysis. ( Abrahamowicz, M; Behlouli, H; Bernatsky, S; Elharram, M; Moura, CS; Pilote, L; Raparelli, V, 2020)
"The global incidence and prevalence of type 2 diabetes have been escalating in recent decades."	1.56	2020 Consensus of Taiwan Society of Cardiology on the pharmacological management of patients with type 2 diabetes and cardiovascular diseases. ( Chang, KC; Chao, TF; Chao, TH; Chen, WJ; Cheng, HM; Cheng, SM; Chiang, CE; Chu, PH; Huang, JL; Hung, HF; Hwang, JJ; Lai, WT; Li, YH; Lin, SJ; Lin, TH; Liu, ME; Liu, PY; Shyu, KG; Sung, SH; Tsai, CD; Ueng, KC; Wang, KL; Wu, YJ; Wu, YW; Yeh, HI; Yeh, SJ; Yin, WH, 2020)
"<6."	1.56	Metformin Should Not Be Used to Treat Prediabetes. ( Davidson, MB, 2020)
"The metformin intoxication was confirmed to be intentional in 23% (n = 5) of the single intoxications."	1.51	Metformin - Postmortem fatal and non-fatal reference concentrations in femoral blood and risk factors associated with fatal intoxications. ( Ahlner, J; Druid, H; Jönsson, AK; Östgren, CJ; Walz, L, 2019)
"Although patients with type 2 diabetes mellitus (T2DM) may fail to achieve adequate hemoglobin A1c (HbA1c) control despite metformin-sulfonylurea (Met-SU) dual therapy, a third-line glucose-lowering medication-including dipeptidyl peptidase-4 inhibitor (DPP4i), insulin, or thiazolidinedione (TZD)-can be added to achieve this."	1.51	Intensification with dipeptidyl peptidase-4 inhibitor, insulin, or thiazolidinediones and risks of all-cause mortality, cardiovascular diseases, and severe hypoglycemia in patients on metformin-sulfonylurea dual therapy: A retrospective cohort study. ( Chan, EW; Ho, CW; Lam, CLK; Man, KKC; Shi, M; Tse, ETY; Wong, CKH; Wong, ICK, 2019)
" The relatively high GDF-15 bioavailability might partly explain the protective cardiovascular effects of metformin."	1.51	Metformin is the key factor in elevated plasma growth differentiation factor-15 levels in type 2 diabetes: A nested, case-control study. ( Dove, F; Gates, PE; Goncalves, I; Gooding, K; Khan, F; Looker, HC; Natali, A; Nesti, L; Nilsson, J; Persson, M; Shore, AC; Venturi, E, 2019)
"Metformin use was statistically significantly associated with higher carotid stiffness as assessed by distensibility coefficient [0."	1.51	Metformin use in type 2 diabetic patients is not associated with lower arterial stiffness: the Maastricht Study. ( de Vries, F; Driessen, JHM; Henry, RMA; Kroon, AA; Reesink, KD; Schalkwijk, C; Schaper, N; Schram, MT; Sep, S; Stehouwer, CDA; van den Bergh, JPW; van der Kallen, C; van Onzenoort, HAW, 2019)
"In the present study, type 2 diabetes was induced in male Goto‑Kakizaki (GK) rats fed with high‑fat diet (HFD)."	1.48	Apelin‑13 ameliorates metabolic and cardiovascular disorders in a rat model of type 2 diabetes with a high‑fat diet. ( Fang, H; Hu, J; Li, M, 2018)
"469 ambulatory type 2 diabetes patients (mean diabetes duration 10."	1.46	Vitamin B12 deficiency is associated with cardiovascular autonomic neuropathy in patients with type 2 diabetes. ( Fleischer, J; Hansen, CS; Jensen, JS; Jørgensen, ME; Ridderstråle, M; Vistisen, D, 2017)
"Plasma PRCP levels are elevated in type 2 diabetes (T2D) mellitus and cardiovascular diseases."	1.46	Altered Prolylcarboxypeptidase Expression and Function in Response to Different Risk Factors of Diabetes. ( Floyd, L; Shariat-Madar, Z; Tabrizian, T, 2017)
"Treatment with glyburide is associated with increased all-cause and cardiovascular mortality in patients with T2DM."	1.46	All-Cause and Cardiovascular Mortality following Treatment with Metformin or Glyburide in Patients with Type 2 Diabetes Mellitus. ( Esteghamati, A; Heidari, B; Larry, M; Mansournia, MA; Nakhjavani, M; Nargesi, AA; Rabizadeh, S; Raee, MR; Zarifkar, M, 2017)
"Only metformin monotherapy was not associated with an increased 5-year mortality compared with matched controls, whereas individuals on a combination of sulfonylurea and insulin had the highest mortality risks."	1.43	Mortality in Individuals Treated With Glucose-Lowering Agents: A Large, Controlled Cohort Study. ( Callens, M; Claesen, M; De Moor, B; De Smet, F; Gillard, P; Mathieu, C, 2016)
"Men with type 2 diabetes are often characterized by abnormal plasma testosterone levels."	1.43	The effect of testosterone on cardiovascular risk factors in men with type 2 diabetes and late-onset hypogonadism treated with metformin or glimepiride. ( Gilowski, W; Krysiak, R; Okopień, B, 2016)
"Myocardial infarction is the most common cause of death in these patients."	1.43	Mortality reduction among persons with type 2 diabetes: (-)-Epicatechin as add-on therapy to metformin? ( Moreno-Ulloa, A; Moreno-Ulloa, J, 2016)
"Metformin was associated with a decreased risk in the cohort with elevated NT-proBNP ≥300 pg/mL (HR 0."	1.43	Cardiovascular safety of metformin and sulfonylureas in patients with different cardiac risk profiles. ( Brath, H; Clodi, M; Francesconi, C; Hülsmann, M; Luger, A; Neuhold, S; Pacher, R; Prager, R; Resl, M; Strunk, G; Vila, G; Wurm, R, 2016)
"Patients with type 2 diabetes who had been on metformin monotherapy and started another agent in addition to metformin were eligible for inclusion."	1.43	Cardiovascular safety of glucose-lowering agents as add-on medication to metformin treatment in type 2 diabetes: report from the Swedish National Diabetes Register. ( Ekström, N; Eliasson, B; Franzén, S; Gudbjörnsdottir, S; Miftaraj, M; Svensson, AM; Zethelius, B, 2016)
"Metformin-glinides was most cost-effective in the base-case analysis; Metformin-glinides saved $194 USD for one percentage point of reduction in CVD risk, as compared to Metformin-SU."	1.43	Comparative cost-effectiveness of metformin-based dual therapies associated with risk of cardiovascular diseases among Chinese patients with type 2 diabetes: Evidence from a population-based national cohort in Taiwan. ( Chen, YT; Liu, YM; Ou, HT; Wu, JS, 2016)
" These results, which do not account for levels of adherence or dosage information and which are subject to confounding by indication, might have implications for prescribing of diabetes drugs."	1.43	Diabetes treatments and risk of heart failure, cardiovascular disease, and all cause mortality: cohort study in primary care. ( Coupland, C; Hippisley-Cox, J, 2016)
"The Cardiff Model was used to simulate disease progression and estimate the long-term effect of treatments on patients."	1.42	Cost-effectiveness of saxagliptin vs glimepiride as a second-line therapy added to metformin in Type 2 diabetes in China. ( Deng, J; Dong, H; Gu, S; Mu, Y; Shi, L, 2015)
"Treatment with metformin resulted in progressive improvement of metabolic status, while blood pressure values normalized with atenolol therapy."	1.40	LMNA gene mutation as a model of cardiometabolic dysfunction: from genetic analysis to treatment response. ( Amorini, M; Arrigo, T; Briuglia, S; Chirico, V; Ferraù, V; Lacquaniti, A; Loddo, I; Salpietro, C; Salpietro, V, 2014)
"Metformin was independently associated with lower prevalence of cardiovascular disease for any age quartile and eGFR category than all other treatments."	1.39	Age, renal dysfunction, cardiovascular disease, and antihyperglycemic treatment in type 2 diabetes mellitus: findings from the Renal Insufficiency and Cardiovascular Events Italian Multicenter Study. ( Bonora, E; Cavalot, F; Cignarelli, M; Ferrannini, E; Fondelli, C; Morano, S; Orsi, E; Penno, G; Pugliese, G; Solini, A; Trevisan, R; Vedovato, M, 2013)
"Metformin treatment increases serum cartonectin levels in these women and in omental AT explants."	1.39	Metformin increases the novel adipokine cartonectin/CTRP3 in women with polycystic ovary syndrome. ( Adya, R; Amar, O; Chen, J; Hu, J; Lehnert, H; Mattu, HS; Patel, V; Ramanjaneya, M; Randeva, HS; Tan, BK, 2013)
"Individuals with type 2 diabetes (T2DM) are at increased risk of cardiovascular disease, including heart failure (HF)."	1.39	Metformin treatment may be associated with decreased levels of NT-proBNP in patients with type 2 diabetes. ( Czlonkowski, A; Filipiak, KJ; Kaplon-Cieslicka, A; Opolski, G; Postula, M; Rosiak, M; Trzepla, E, 2013)
"A cohort of 32 871 patients with Type 2 diabetes aged 35 years and older identified by extracting data from electronic patient records for all patients who had a diagnosis of Type 2 diabetes and had glucose-lowering agents prescribed between 1999 and 2009 at 84 primary care centres in Sweden."	1.39	Associations of HbA1c and educational level with risk of cardiovascular events in 32,871 drug-treated patients with Type 2 diabetes: a cohort study in primary care. ( Johansson, G; Lohm, L; Nilsson, PM; Östgren, CJ; Sundström, J; Svennblad, B, 2013)
"Obesity is a common problem and its health consequences depend on the phenotype of obesity."	1.38	Menopausal obesity and metabolic syndrome - PolSenior study. ( Milewicz, A, 2012)
"Metformin was not associated with the improvement in total cholesterol level (adjusted mean difference; 30."	1.37	Total cholesterol, high density lipoprotein and triglyceride for cardiovascular disease in elderly patients treated with metformin. ( Jung, KH; Kim, JY; Sin, HY, 2011)
"Metformin is an antihyperglycemic agent commonly used in diabetic patients."	1.37	The nephrologist's role in metformin-induced lactic acidosis. ( Basterrechea, MA; de Arriba, G; Gómez-Navarro, L; Hernández-Sevillano, B; Pérez del Valle, KM; Rodríguez-Palomares, JR; Sánchez-Heras, M; Tallón, S; Torres-Guinea, M, 2011)
"Management of type 2 diabetes mellitus (T2DM) can be challenging."	1.36	New therapeutic options: management strategies to optimize glycemic control. ( Freeman, JS, 2010)
"The prevalence of type 2 diabetes in Thailand is 9."	1.36	Thailand Diabetic Registry cohort: predicting death in Thai diabetic patients and causes of death. ( Benjasuratwong, Y; Bunnag, P; Chetthakul, T; Deerochanawong, C; Komoltri, C; Kosachunhanun, N; Krittiyawong, S; Leelawatana, R; Mongkolsomlit, S; Ngarmukos, C; Plengvidhya, N; Pratipanawatr, T; Rawdaree, P; Suwanwalaikorn, S, 2010)
"Obese patients with type 2 diabetes and impaired glucose tolerance are at increased risk of development of cardiovascular diseases."	1.35	Effects of basal insulin analog and metformin on glycaemia control and weight as risk factors for endothelial dysfunction. ( Ascić-Buturović, B; Kacila, M, 2008)
"The diabetic patient, when type 2 diabetes is newly diagnosed, raises a therapeutic problem commonly observed in clinical practice, which is more complex than expected at first glance."	1.35	[Optimisation of pharmacological therapy in a patient with a newly diagnosed type 2 diabetes]. ( De Flines, J; Jandrain, BJ; Radermecker, RP; Scheen, AJ, 2009)
"Metformin has now been established as the drug of choice for the first-line management of type 2 diabetes mellitus."	1.35	Metformin: diamonds are forever. ( Maltezos, E; Mikhailidis, DP; Papanas, N, 2009)
"In clinical trials in patients with type 2 diabetes mellitus, pioglitazone as monotherapy, or in combination with metformin, repaglinide, insulin, or a sulfonylurea, induced both long- and short-term improvements in glycemic control and serum lipid profiles."	1.33	Spotlight on pioglitazone in type 2 diabetes mellitus. ( Easthope, S; Keating, GM; Plosker, GL; Robinson, DM; Waugh, J, 2006)
"Hirsutism is the manifestation of hyperandrogenemia in PCOS."	1.32	The treatment of polycystic ovary syndrome. ( Ajossa, S; Guerriero, S; Melis, GB; Orrù, M; Paoletti, AM, 2004)
"Their underlying insulin resistance is determined with the help of a checklist and a method called homeostasis model assessment (HOMA)."	1.32	[Diabetes update: preventing type 2 diabetes. Individualized stepwise therapy (oral antidiabetic agents). Multifactorial intervention]. ( Müller, B; Trepp, R, 2004)
"The increasing incidence of type 2 diabetes constitutes a considerable individual and socio-economic risk, therefore preventive concepts are urgently needed."	1.32	[Primary prevention of diabetes mellitus type 2]. ( Gallwitz, B, 2004)
"Because both type 2 diabetes and elevated plasma lipid levels are important independent risk factors for cardiovascular disease and coronary heart disease, the choice of an antihyperglycemic agent for patients with type 2 diabetes--in whom abnormal plasma lipid levels are often seen-should take into account effects on lipids as well as on markers of glycemic control."	1.31	Lipid effects of glyburide/metformin tablets in patients with type 2 diabetes mellitus with poor glycemic control and dyslipidemia in an open-label extension study. ( Dailey, GE; Fiedorek, FT; Mohideen, P, 2002)

Research

Studies (594)

Authors

Clinical Trials (122)

Trial Overview

Trial Outcomes

Development of Diabetes.

Timeframe	Studies, this research(%)	All Research%
pre-1990	1 (0.17)	18.7374
1990's	16 (2.69)	18.2507
2000's	137 (23.06)	29.6817
2010's	294 (49.49)	24.3611
2020's	146 (24.58)	2.80

Authors	Studies
Koufakis, T	3
Papazafiropoulou, A	2
Makrilakis, K	1
Kotsa, K	3
Ding, Y	1
Zhou, Y	1
Ling, P	1
Feng, X	2
Luo, S	2
Zheng, X	1
Little, PJ	2
Xu, S	2
Weng, J	1
Lee, CG	1
Heckman-Stoddard, B	1
Dabelea, D	2
Gadde, KM	2
Ehrmann, D	1
Ford, L	1
Prorok, P	1
Boyko, EJ	1
Pi-Sunyer, X	2
Wallia, A	1
Knowler, WC	4
Crandall, JP	2
Temprosa, M	5
Lavalle-Cobo, A	2
Masson, W	2
Lobo, M	2
Masson, G	2
Molinero, G	2
Hedayati, N	1
Oskouei, Z	1
Tabeshpour, J	1
Naeini, MB	1
Bazo-Alvarez, JC	1
Pal, K	1
Pham, TM	1
Nazareth, I	1
Petersen, I	1
Sharma, M	1
Sim, R	1
Chong, CW	1
Loganadan, NK	1
Fong, AYY	1
Navaravong, L	1
Hussein, Z	1
Khunti, K	3
Lee, SWH	1
Shin, H	3
Schneeweiss, S	3
Glynn, RJ	4
Patorno, E	5
Howlett, LA	1
Jones, SA	1
Lancaster, MK	1
Li, T	2
Providencia, R	2
Jiang, W	1
Liu, M	2
Yu, L	2
Gu, C	2
Chang, ACY	1
Ma, H	3
Schernthaner, G	3
Brand, K	2
Bailey, CJ	2
Tardif, I	1
Guénette, L	2
Zongo, A	1
Demers, É	1
Lunghi, C	1
Lasalvia, P	1
Gil-Rojas, Y	1
García, Á	1
Dagogo-Jack, S	3
Cannon, CP	2
Cherney, DZI	2
Cosentino, F	2
Liu, J	4
Pong, A	1
Gantz, I	2
Frederich, R	3
Mancuso, JP	2
Pratley, RE	2
Agarwal, SM	1
Stogios, N	1
Dardano, A	1
Aragona, M	1
Daniele, G	2
Miccoli, R	2
Del Prato, S	5
Elbarbary, NS	1
Ismail, EAR	1
Ghallab, MA	1
Husain, M	2
Consoli, A	3
De Remigis, A	1
Pettersson Meyer, AS	1
Rasmussen, S	2
Bain, S	1
Wong, CKH	2
Lau, KTK	1
Tang, EHM	1
Lee, CH	1
Lee, CYY	1
Woo, YC	2
Au, ICH	1
Tan, KCB	1
Lui, DTW	1
Gillani, SW	2
Syed Sulaiman, SA	1
Menon, V	1
Rahamathullah, N	1
Elshafie, RM	1
Rathore, HA	1
Gottwald-Hostalek, U	1
Gwilt, M	1
Wilson, C	3
Carpenter, J	1
Park, S	2
McHugh, C	2
Scott, EM	2
Hickie, IB	2
Maldonado, M	1
Cater, NB	1
Wang, S	4
McGuire, DK	5
Hafidh, K	1
Malek, R	2
Al-Rubeaan, K	1
Kok, A	1
Bayram, F	1
Echtay, A	1
Rajadhyaksha, V	1
Hadaoui, A	1
Müller-Werdan, U	1
Bu, Y	1
Peng, M	1
Tang, X	2
Xu, X	3
Wu, Y	2
Chen, AF	1
Yang, X	3
Poznyak, AV	1
Litvinova, L	1
Poggio, P	1
Moschetta, D	1
Sukhorukov, VN	1
Orekhov, AN	1
Kamel, AM	1
Sabry, N	1
Farid, S	1
Rydén, L	4
Standl, E	3
Nathan, DM	4
Lachin, JM	2
Bebu, I	1
Burch, HB	1
Buse, JB	3
Cherrington, AL	1
Fortmann, SP	1
Green, JB	2
Kahn, SE	5
Kirkman, MS	1
Krause-Steinrauf, H	1
Larkin, ME	1
Phillips, LS	1
Pop-Busui, R	2
Steffes, M	1
Tiktin, M	1
Tripputi, M	1
Wexler, DJ	1
Younes, N	1
Li, C	2
Wang, D	2
Jiang, Z	1
Gao, Y	3
Sun, L	1
Li, R	1
Chen, M	2
Lin, C	1
Liu, D	1
Mc Namara, KP	1
Alzubaidi, H	1
Murray, M	1
Samorinha, C	1
Dunbar, JA	1
Versace, VL	1
Castle, D	1
Mannucci, E	4
Gallo, M	1
Giaccari, A	1
Candido, R	2
Pintaudi, B	2
Targher, G	2
Monami, M	3
Brinkworth, GD	1
Wycherley, TP	1
Taylor, PJ	1
Thompson, CH	1
Nazu, NA	1
Wikström, K	1
Lamidi, ML	1
Lindström, J	1
Tirkkonen, H	1
Rautiainen, P	1
Laatikainen, T	1
Li, H	7
Chang, GY	3
Jiang, YH	3
Xu, L	4
Shen, L	3
Gu, ZC	3
Lin, HW	3
Shi, FH	3
Naseri, A	2
Sanaie, S	2
Hamzehzadeh, S	2
Seyedi-Sahebari, S	2
Hosseini, MS	2
Gholipour-Khalili, E	2
Rezazadeh-Gavgani, E	4
Majidazar, R	2
Seraji, P	2
Daneshvar, S	2
Qiu, M	1
Paridari, P	1
Jabermoradi, S	1
Gholamzadeh, R	1
Vazifekhah, S	1
Vazirizadeh-Mahabadi, M	1
Roshdi Dizaji, S	1
Forouzannia, SA	1
Hosseini, M	1
Yousefifard, M	1
Siriyotha, S	1
Lukkunaprasit, T	1
Angkananard, T	1
Looareesuwan, P	1
McKay, GJ	1
Attia, J	1
Thakkinstian, A	1
Carpenter, JS	1
Nichles, A	1
Zmicerevska, N	1
Song, YJC	1
Hamilton, B	1
Hockey, S	1
Crouse, J	1
Koethe, D	1
Wancewicz, B	1
Zhu, Y	3
Fenske, RJ	1
Weeks, AM	1
Wenger, K	1
Pabich, S	1
Daniels, M	1
Punt, M	1
Nall, R	1
Peter, DC	1
Brasier, A	1
Cox, ED	1
Davis, DB	1
Ge, Y	1
Kimple, ME	1
Dihoum, A	1
Rena, G	3
Pearson, ER	1
Lang, CC	5
Mordi, IR	3
Ebell, MH	1
Vatier, C	1
Bourcigaux, N	1
Aktas, G	1
Atak Tel, BM	1
Tel, R	1
Balci, B	1
Santos, C	1
Brito-Costa, S	1
Margalho, L	1
Monteiro, P	1
Hambly, R	1
Kearney, N	1
Hughes, R	1
Fletcher, JM	1
Kirby, B	1
Bica, IC	1
Pietroșel, VA	1
Salmen, T	1
Diaconu, CT	1
Fierbinteanu Braticevici, C	1
Stoica, RA	1
Suceveanu, AI	1
Pantea Stoian, A	1
Stevenson-Hoare, J	1
Leonenko, G	1
Escott-Price, V	1
Brønden, A	1
Christensen, MB	1
Glintborg, D	2
Snorgaard, O	1
Kofoed-Enevoldsen, A	1
Madsen, GK	1
Toft, K	1
Kristensen, JK	1
Højlund, K	1
Hansen, TK	1
Søndergaard, E	1
Hansen, KB	1
Foresta, A	1
Succurro, E	1
Baviera, M	1
Macaluso, G	1
Ojeda-Fernández, L	1
Carla Roncaglioni, M	1
Fortino, I	1
Nobili, A	1
Sesti, G	3
Luo, J	1
Feldman, R	1
Callaway Kim, K	1
Rothenberger, S	1
Korytkowski, M	1
Hernandez, I	1
Gellad, WF	1
Li, JZ	1
Li, YR	2
Abrahami, D	1
D'Andrea, E	1
Yin, H	3
Kim, SC	2
Paik, JM	1
Wexler, D	1
Azoulay, L	4
Oikonomou, E	1
Xenou, M	1
Zakynthinos, GE	1
Tsaplaris, P	1
Lampsas, S	1
Bletsa, E	1
Gialamas, I	1
Kalogeras, K	1
Goliopoulou, A	1
Gounaridi, MI	1
Pesiridis, T	1
Tsatsaragkou, A	1
Vavouranakis, M	1
Siasos, G	1
Tousoulis, D	1
Horii, T	1
Oikawa, Y	1
Shimada, A	1
Mihara, K	1
Bakhashab, S	1
Megantara, HP	1
Mahaputra, DK	1
O'Neill, J	1
Phowira, J	1
Weaver, JU	1
Kender, Z	1
Groener, JB	1
Reismann, P	1
Kopf, S	1
Barnett, R	1
Walz, L	1
Jönsson, AK	1
Ahlner, J	1
Östgren, CJ	3
Druid, H	1
Hedrington, MS	1
Davis, SN	2
Merino, J	1
Jablonski, KA	2
Mercader, JM	1
Chen, L	4
Harden, M	1
Delahanty, LM	2
Araneta, MRG	1
Walford, GA	1
Jacobs, SBR	1
Ibebuogu, UN	1
Franks, PW	2
Florez, JC	2
Wu, L	1
Gunton, JE	1
Prattichizzo, F	3
La Sala, L	2
Marx, N	5
Ferrini, M	1
Valensi, P	1
Ceriello, A	4
Heintjes, EM	1
Houben, E	1
Beekman-Hendriks, WL	1
Lighaam, E	1
Cremers, SM	1
Penning-van Beest, FJA	1
Stehouwer, CDA	3
Herings, RMC	1
Luo, Y	1
Chen, J	5
Gao, X	1
Yang, W	2
Zou, X	1
Zhou, X	3
Ji, L	1
Man, KKC	1
Shi, M	1
Chan, EW	1
Ho, CW	1
Tse, ETY	1
Wong, ICK	2
Lam, CLK	1
Raparelli, V	2
Elharram, M	2
Moura, CS	2
Abrahamowicz, M	2
Bernatsky, S	2
Behlouli, H	2
Pilote, L	2
Whitlock, RH	1
Hougen, I	1
Komenda, P	1
Rigatto, C	1
Clemens, KK	1
Tangri, N	1
Zhang, K	1
Dai, H	1
Deng, Z	1
Komaru, Y	1
Takeuchi, T	1
Suzuki, L	1
Asano, T	1
Urayama, KY	1
Salvatore, T	1
Pafundi, PC	1
Morgillo, F	1
Di Liello, R	1
Galiero, R	1
Nevola, R	1
Marfella, R	1
Monaco, L	1
Rinaldi, L	1
Adinolfi, LE	1
Sasso, FC	1
Petrie, JR	2
Rossing, PR	1
Campbell, IW	1
Markowicz-Piasecka, M	2
Sadkowska, A	1
Huttunen, KM	2
Podsiedlik, M	2
Mikiciuk-Olasik, E	1
Sikora, J	2
Cordero-Herrera, I	1
Guimarães, DD	1
Moretti, C	1
Zhuge, Z	1
Han, H	1
McCann Haworth, S	1
Uribe Gonzalez, AE	1
Andersson, DC	1
Weitzberg, E	1
Lundberg, JO	1
Carlström, M	1
Chiang, CE	2
Wang, KL	2
Cheng, HM	3
Sung, SH	3
Chao, TF	2
Gelosa, P	1
Castiglioni, L	1
Camera, M	1
Sironi, L	1
Le, P	1
Chaitoff, A	1
Misra-Hebert, AD	1
Ye, W	1
Herman, WH	2
Rothberg, MB	1
Jensen, MH	1
Kjolby, M	1
Hejlesen, O	1
Jakobsen, PE	1
Vestergaard, P	1
Tagi, VM	1
Samvelyan, S	1
Chiarelli, F	2
Indhavivadhana, S	1
Rattanachaiyanont, M	1
Wongwananurak, T	1
Techatraisak, K	1
Jirattigalachote, A	1
Dangrat, C	1
Elsisi, GH	1
Anwar, MM	1
Khattab, M	1
Elebrashy, I	1
Wafa, A	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
[NCT00004992]	Phase 3	3,234 participants (Actual)	Interventional	1996-07-31	Completed
Diabetes Prevention Program Outcomes Study[NCT00038727]	Phase 3	2,779 participants (Actual)	Interventional	2002-09-30	Active, not recruiting
Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess Cardiovascular Outcomes Following Treatment With Ertugliflozin (MK-8835/PF-04971729) in Subjects With Type 2 Diabetes Mellitus and Established Vascular Disease, The VERTIS CV Stu[NCT01986881]	Phase 3	8,246 participants (Actual)	Interventional	2013-11-04	Completed
A Long-term, Randomised, Double-blind, Placebo-controlled, Multinational, Multi-centre Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN™ 6 - Long-term Outcomes)[NCT01720446]	Phase 3	3,297 participants (Actual)	Interventional	2013-02-21	Completed
A Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes[NCT02692716]	Phase 3	3,183 participants (Actual)	Interventional	2017-01-17	Completed
Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study[NCT01794143]	Phase 3	5,047 participants (Actual)	Interventional	2013-05-31	Completed
Study of Metformin Overdose in Adult Patients Treated at the University Hospital of Nancy: Single-center Descriptive Retrospective Observational Study[NCT04762966]		50 participants (Anticipated)	Observational	2021-03-01	Recruiting
Safety and Efficacy of Adding Dapagliflozin and Furosemide in Diabetic Patients (Type 2) With Decompensated Heart Failure With Reduced Ejection Fraction (HFrEF)[NCT04385589]	Phase 4	100 participants (Actual)	Interventional	2020-05-01	Completed
A Multicentric, Randomized, Open Label Study on Comparison of Pancreatic Beta Cell Recovery and Preservation in Type 2 Diabetic Patients Treated With DPP-4 Inhibitor (Vildagliptin) and Metformin[NCT02853630]	Phase 4	203 participants (Actual)	Interventional	2013-12-31	Completed
A 52 Week Randomized, Double-Blind, Multicenter, Mechanistic Study With a 24 Week Open-Label Follow-Up to Evaluate the Effect of AVANDIA TM on Bone in Postmenopausal Women With Type 2 Diabetes Mellitus[NCT00679939]	Phase 4	226 participants (Actual)	Interventional	2008-04-21	Completed
[NCT00396851]		100 participants	Interventional	2007-01-31	Not yet recruiting
Efficacy and Safety of Vildagliptin Compared to Metformin in Drug Naive Patients With Type 2 Diabetes[NCT00099866]	Phase 3	570 participants (Actual)	Interventional	2004-01-31	Completed
Extension to a Study on the Efficacy and Safety of Vildagliptin Compared to Metformin in Drug Naive Patients With Type 2 Diabetes[NCT00138567]	Phase 3	530 participants	Interventional	2005-01-31	Completed
A Randomized, Double-Blind Study to Compare the Durability of Glucose Lowering and Preservation of Pancreatic Beta-Cell Function of Rosiglitazone Monotherapy Compared to Metformin or Glyburide/Glibenclamide in Patients With Drug-Naive, Recently Diagnosed [NCT00279045]	Phase 3	4,426 participants (Actual)	Interventional	2000-01-03	Completed
Effects of Agonists of Glucagon Like Peptide - 1 Receptors (GLP-1R) on Arterial Stiffness, Endothelial Glycocalyx and Coronary Flow Reserve in Patients With Coronary Artery Disease and Patients With Diabetes Mellitus[NCT03010683]		60 participants (Actual)	Interventional	2015-11-30	Completed
Metabolic Effects of Treatment in Patients With Recently Diagnosed Type 2 Diabetes[NCT00373178]	Phase 4	100 participants (Actual)	Interventional	2005-01-31	Completed
Double Blind Comparison Study of JARDIANCE® (Empagliflozin) in Prehypertensives Type II Diabetics With Metformin[NCT01001962]	Phase 4	1,054 participants (Anticipated)	Interventional	2016-01-31	Not yet recruiting
A Multicenter, Randomized, Double-Blind Active-Controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin in Combination With Metformin IR as Initial Therapy Compared to Saxagliptin Monotherapy and to Metformin IR Monotherapy in Subjects[NCT00327015]	Phase 3	1,306 participants (Actual)	Interventional	2006-05-31	Completed
A Multicenter, Randomized, Double-Blind Factorial Study of the Co-Administration of MK0431 and Metformin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control[NCT00103857]	Phase 3	1,208 participants (Actual)	Interventional	2005-03-17	Completed
[NCT00035568]	Phase 4	0 participants	Interventional	2002-02-28	Completed
A Multicenter, Register-based, Randomized, Controlled Trial Comparing Dapagliflozin With Metformin Treatment in Early Stage Type 2 Diabetes Patients by Assessing Mortality and Macro- and Microvascular Complications[NCT03982381]	Phase 4	2,067 participants (Actual)	Interventional	2019-09-05	Active, not recruiting
Restoring Insulin Secretion Adult Medication Study[NCT01779362]	Phase 3	267 participants (Actual)	Interventional	2013-04-30	Completed
The Impact of LY2189265 Versus Metformin on Glycemic Control in Early Type 2 Diabetes Mellitus (AWARD-3: Assessment of Weekly AdministRation of LY2189265 in Diabetes-3)[NCT01126580]	Phase 3	807 participants (Actual)	Interventional	2010-05-31	Completed
A Long-term, Multi-centre, International, Randomised Double-blind, Placebo-controlled Trial to Determine Liraglutide Effects on Cardiovascular Events[NCT01179048]	Phase 3	9,341 participants (Actual)	Interventional	2010-08-31	Completed
Long-term Role of Pioglitazone in Non-Alcoholic Fatty Liver Disease (NAFLD) in Type 2 Diabetes Mellitus (T2DM).[NCT00994682]	Phase 4	176 participants (Actual)	Interventional	2008-12-31	Completed
A Phase 4, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Pioglitazone Compared to Placebo on Bone Metabolism in Impaired Fasting Glucose, Postmenopausal Women for One Year of Treatment[NCT00708175]	Phase 4	156 participants (Actual)	Interventional	2008-05-31	Completed
A Clinical Trial to Prevent the Complications of Insulin Resistance (Including Type-2 Diabetes)[NCT00015626]	Phase 2	300 participants	Interventional		Completed
[NCT00276497]	Phase 1	0 participants	Interventional	2003-10-31	Completed
Effect of Pioglitazone on Intima Media Thickness, Endothelial Function, and Heart Rate Variability in Patients With Impaired Glucose Tolerance[NCT00306826]	Phase 4	120 participants	Interventional		Withdrawn (stopped due to financial support withdrawn)
Role of Pioglitazone and Berberine in Treatment of Non-alcoholic Fatty Liver Disease(NAFLD) Patients With Impaired Glucose Regulation or Type 2 Diabetes Mellitus[NCT00633282]	Phase 2	184 participants (Actual)	Interventional	2008-03-31	Completed
Actos Now for Prevention of Diabetes (ACT NOW)[NCT00220961]	Phase 3	602 participants (Actual)	Interventional	2004-01-31	Completed
DPP-4 Inhibition and Thiazolidinedione for Diabetes Mellitus Prevention (DInT DM Study)[NCT01006018]		3 participants (Actual)	Interventional	2011-07-31	Terminated (stopped due to Unanticipated delays due to sterilization/stabilization testing of GLP-1.)
Effects of GH and Pioglitazone in Viscerally Obese Adults With IGT[NCT00352287]	Phase 4	60 participants	Interventional	2003-03-31	Completed
Detection of Plaque Inflammation and Visualization of Anti-Inflammatory Effects of Pioglitazone on Plaque Inflammation in Subjects With Impaired Glucose Tolerance and Type 2 Diabetes Mellitus by FDG-PET/CT[NCT00722631]		70 participants (Actual)	Interventional	2007-05-31	Completed
Effects of PPAR Ligands on Ectopic Fat Accumulation and Inflammation in Subjects With Impaired Glucose Tolerance[NCT00470262]		27 participants (Actual)	Interventional	2007-01-31	Completed
Effect of Dapagliflozin, Metformin and Physical Activity on Glucose Variability, Body Composition and Cardiovascular Risk in Pre-diabetes[NCT02695810]	Phase 2	120 participants (Actual)	Interventional	2016-02-24	Completed
Effectiveness of the Treatment With Dapagliflozin and Metformin Compared to Metformin Monotherapy for Weight Loss on Diabetic and Prediabetic Patients With Obesity Class III[NCT03968224]	Phase 2/Phase 3	90 participants (Anticipated)	Interventional	2018-07-07	Recruiting
Effects on Incidence of Cardiovascular Events of the Addition of Pioglitazone as Compared With a Sulphonylurea in Type 2 Diabetic Patients Inadequately Controlled With Metformin.[NCT00700856]	Phase 4	3,371 participants (Anticipated)	Interventional	2008-09-30	Active, not recruiting
Association Between Glycaemic Control and Morbi/Mortality After 5 Years of Follow-up in Type 2 Diabetic Patients[NCT01282060]		986 participants (Actual)	Observational	2009-03-31	Active, not recruiting
Effect of Oral Supplementation With Curcumin on Insulin Sensitivity in Subjects With Prediabetes[NCT03917784]	Phase 4	142 participants (Anticipated)	Interventional	2019-02-25	Recruiting
Studies to Treat Or Prevent Pediatric Type 2 Diabetes (STOPP-T2D) Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Clinical Trial[NCT00081328]	Phase 3	699 participants (Actual)	Interventional	2004-05-31	Completed
The LANCET Trial: A Randomized Clinical Trial of Lantus for C-reactive Protein Reduction in Early Treatment of Type 2 Diabetes[NCT00366301]	Phase 4	500 participants (Actual)	Interventional	2006-08-31	Terminated (stopped due to Interim analyses demonstrated futility. Thus, recruitment curtailed 10/08.)
A Multicenter, International Randomized, 2x2 Factorial Design Study to Evaluate the Effects of Lantus (Insulin Glargine) Versus Standard Care, and of Omega-3 Fatty Acids Versus Placebo, in Reducing Cardiovascular Morbidity and Mortality in High Risk Peopl[NCT00069784]	Phase 3	12,537 participants (Actual)	Interventional	2003-08-31	Completed
The Effect of Empagliflozin Versus Metformin on Hormonal, Metabolic and Cardiovascular Risk Factors in Patients With Polycystic Ovary Syndrome (PCOS) - a Randomised Open-label Parallel Study.[NCT03008551]	Phase 2/Phase 3	40 participants (Actual)	Interventional	2017-08-18	Completed
The Efficacy of Canagliflozin Versus Metformin in Women With Polycystic Ovary Syndrome: A Randomized, Open Label Trial[NCT04700839]	Phase 4	68 participants (Actual)	Interventional	2020-05-01	Completed
A Multi-center, Prospective, Cohort Study to Elucidate the Effects of Metformin Treatment on Steroid Hormones and Social Behavior. Linking Autistic Behaviorial Symptoms to Changes in Steroid Hormone Availability[NCT04930471]		45 participants (Anticipated)	Observational	2021-06-30	Not yet recruiting
The Emirates Heart Health Project: A Stepped-wedge Cluster Randomized-controlled Trial of a Family-based Health Coach Guided Dietary and Exercise Intervention for Reducing Weight and Cardiovascular Risk in Overweight and Obese Adult Nationals of the Unite[NCT04688684]		80 participants (Anticipated)	Interventional	2022-06-01	Not yet recruiting
Action to Control Cardiovascular Risk in Diabetes (ACCORD)[NCT00000620]	Phase 3	10,251 participants (Actual)	Interventional	1999-09-30	Completed
Exercise Dose and Metformin for Vascular Health in Adults With Metabolic Syndrome[NCT03355469]	Phase 2/Phase 3	80 participants (Anticipated)	Interventional	2017-08-07	Recruiting
CSP #465 - Glycemic Control and Complications in Diabetes Mellitus Type 2 (VADT)[NCT00032487]	Phase 3	1,791 participants (Actual)	Interventional	2000-12-01	Completed
CSP #465A - Non-Traditional Cardiovascular Risk Factors And Atherosclerosis In Type 2 Diabetes[NCT00256607]		301 participants (Actual)	Observational	2007-06-30	Completed
A Randomised Controlled International Multicentre Study Evaluating Changes in Metabolic Syndrome in Smokers With Type 2 Diabetes Mellitus After Switching From Tobacco Cigarettes to Combustion-Free Nicotine Delivery Systems: DIASMOKE Study[NCT04231838]		576 participants (Anticipated)	Interventional	2021-09-27	Recruiting
TECOS: A Randomized, Placebo Controlled Clinical Trial to Evaluate Cardiovascular Outcomes After Treatment With Sitagliptin in Patients With Type 2 Diabetes Mellitus and Inadequate Glycemic Control[NCT00790205]	Phase 3	14,671 participants (Actual)	Interventional	2008-12-10	Completed
Effect of Saxagliptin in Addition to Dapagliflozin and Metformin on Insulin Resistance, Islet Cell Dysfunction, and Metabolic Control in Subjects With Type 2 Diabetes Mellitus on Previous Metformin Treatment[NCT02304081]	Phase 4	64 participants (Actual)	Interventional	2015-01-31	Completed
A Multicenter, Randomized, Double-Blind, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin Added to Insulin Monotherapy or to Insulin in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Ins[NCT00757588]	Phase 3	455 participants (Actual)	Interventional	2008-11-30	Completed
A 52-Week International, Multi-centre, Randomized, Parallel-group, Double-blind, Active-controlled, Phase III Study With a 52-Week Extension Period to Evaluate the Safety and Efficacy of Saxagliptin in Combination With Metformin Compared With Sulphonylure[NCT00575588]	Phase 3	891 participants (Actual)	Interventional	2007-12-31	Completed
BIO-2-HEART Study (Identifying New BIOmarkers in Patients With Type 2 Diabetes Mellitus and HEArt Failure Receiving Cardiac Resynchronization Therapy Device Implantation)[NCT03323216]		200 participants (Anticipated)	Observational	2018-04-01	Recruiting
Long Term Treatment With Exenatide Versus Glimepiride in Patients With Type 2 Diabetes Pretreated With Metformin (EUREXA: European Exenatide Study)[NCT00359762]	Phase 3	1,029 participants (Actual)	Interventional	2006-09-30	Completed
"Randomized, Double-blind, Placebo-controlled Study to Assess the Effect of Metformin, an Activator of AMPK, on Cognitive Measures of Progression in Huntington's Disease Patients"[NCT04826692]	Phase 3	60 participants (Anticipated)	Interventional	2021-12-10	Recruiting
Efficacy and Safety of the Oral Combined Therapy Glimepiride / Vildagliptin / Metformin in Patients With Type 2 Diabetes With Dual Treatment Failure[NCT04841096]	Phase 3	172 participants (Anticipated)	Interventional	2023-03-21	Recruiting
FLAT-SUGAR: FLuctuATion Reduction With inSULin and Glp-1 Added togetheR[NCT01524705]	Phase 4	102 participants (Actual)	Interventional	2012-08-31	Completed
Using Closed-Loop Artificial Pancreas Technology to Reduce Glycemic Variability and Subsequently Improve Cardiovascular Health in Type 1 Diabetes[NCT05653518]		40 participants (Anticipated)	Interventional	2023-09-09	Recruiting
A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial in China to Study the Safety and Efficacy of the Addition of Sitagliptin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Sulfonylurea T[NCT01590771]	Phase 3	498 participants (Actual)	Interventional	2012-07-09	Completed
A Randomized, Double-Blind, Placebo-Controlled Trial to Assess Safety and Tolerability During Treatment of Type 2 Diabetes (T2DM) With Usual Diabetes Therapy (UDT) and Either Cycloset or Placebo[NCT00377676]	Phase 3	3,095 participants (Actual)	Interventional	2004-07-31	Completed
Effect of an Intervention Program With Healthy Habits Plus Metformin or Conjugated Linoleic Acid Over Clinical Parameters and Molecular Pathways of Insulin Resistance in Obese Pediatric Patients[NCT02063802]	Phase 2	120 participants (Anticipated)	Interventional	2012-08-31	Recruiting
Effect of Liraglutide on Epicardial Fat in Subjects With Type 2 Diabetes[NCT02014740]	Phase 4	100 participants (Actual)	Interventional	2014-03-31	Completed
A Randomized, Long-Term, Open-Label, 3-Arm, Multicenter Study to Compare the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly Suspension to Sitagliptin and Placebo in Subjects With Type 2 Diabetes Mellitus[NCT01652729]	Phase 3	365 participants (Actual)	Interventional	2013-02-28	Completed
Metabolic Effect of Metformin in Obese Insulin Resistant Adolescents With Normal Glucose Tolerance[NCT00667498]	Phase 4	28 participants (Actual)	Interventional	2004-03-31	Completed
A Randomized Trial of Metformin as Adjunct Therapy for Overweight Adolescents With Type 1 Diabetes[NCT01881828]	Phase 3	164 participants (Actual)	Interventional	2013-09-30	Completed
Implementation of a Pragmatic Approach to Lower Diabetes Mellitus Risk After a Diagnosis of Gestational Diabetes Mellitus[NCT05280496]	Phase 3	36 participants (Anticipated)	Interventional	2022-06-01	Recruiting
Effect of Metformin on Healthy Live Birth After In-vitro Fertilization in Women With Prediabetes Mellitus: a Multicenter Double-blind Placebo Controlled Randomized Trial[NCT06064669]		988 participants (Anticipated)	Interventional	2023-10-01	Not yet recruiting
Face-it: A Health Promotion Intervention for Women With Prior Gestational Diabetes and Their Families - A Randomised Controlled Trial[NCT03997773]		277 participants (Actual)	Interventional	2019-05-21	Active, not recruiting
Effect of Myoinositol on Serum Asprosin Levels in PCOS Patients[NCT05951309]		30 participants (Actual)	Interventional	2021-09-01	Completed
Effectiveness of the Combination Liraglutide and Metformin on Weight Loss, Metabolic - Endocrine Parameters and Pregnancy Rate in Women With Polycystic Ovarian Syndrome, Obesity and Infertility[NCT05952882]	Phase 3	188 participants (Anticipated)	Interventional	2023-11-01	Not yet recruiting
Prevalence of NAFLD and Correlation With Its Main Risk Factors Among Egyptian Multicenter National Study[NCT04081571]		1,080 participants (Anticipated)	Observational	2019-04-01	Recruiting
Does Glycated Hemoglobin Variability in Type 2 Diabetes Differ Depending on the Diabetes Treatment Threshold Used in the Qatari Population: Implication on Diabetes Complication Risk?[NCT02879409]		150 participants (Anticipated)	Interventional	2016-11-30	Active, not recruiting
Allopurinol in the Treatment of Patients With Diabetes Mellitus and Multivessel Coronary Artery Disease Treated by Either PCI or CABG: Pilot Study[NCT03700645]	Phase 4	100 participants (Anticipated)	Interventional	2018-12-01	Not yet recruiting
24 Week Open Label, Single Arm Study of Colesevelam in High Risk South Asians With Suboptimal LDL-c Levels Despite Maximally Tolerated Statin Therapy[NCT02504736]		90 participants (Actual)	Observational	2015-06-30	Completed
Comprehensive Treatment of Angina in Women With Microvascular Dysfunction - a Proof of Concept Study of the iPower Cohort[NCT02910154]		62 participants (Actual)	Interventional	2016-12-31	Completed
The Impact of Consumption of Eggs in the Context of Plant-Based Diets on[NCT04316429]		35 participants (Actual)	Interventional	2020-06-09	Completed
WellStart Type 2 Diabetes Study[NCT03731533]		0 participants (Actual)	Interventional	2018-12-01	Withdrawn (stopped due to Grantor withdrew from study)
Metabolic Syndrome and Severe Obesity: Randomized Nutritional Trial to Study Long Term Effect of Very-low-calories Ketogenic Diet (VLCKD) on Weight Control and Cardiovascular Risk Factors[NCT05781269]		100 participants (Anticipated)	Interventional	2022-02-20	Recruiting
Benefits of Adding Continuous Glucose Monitoring to Glycemic Load, Exercise, and Monitoring of Blood Glucose (GEM) for Adults With Type 2 Diabetes - Phase 2[NCT03207893]		24 participants (Actual)	Interventional	2018-07-19	Completed
Treating Type 2 Diabetes by Reducing Postprandial Glucose Elevations: A Paradigm Shift in Lifestyle Modification[NCT03196895]		192 participants (Actual)	Interventional	2017-06-28	Completed
Personalizing Sleep Interventions to Prevent Type 2 Diabetes in Community Dwelling Adults With Pre-Diabetes[NCT03398902]		150 participants (Anticipated)	Interventional	2020-09-01	Recruiting
Assessment of Designer Functional Foods on Parameters of Metabolic and Vascular Status in Individuals With Prediabetes.[NCT02400450]		0 participants (Actual)	Interventional	2016-09-30	Withdrawn
Effect of Simvastatin and Metformin on Clinical, Endocrine, Metabolic and Endothelial Function of Women With Polycystic Ovary Syndrome: Prospective Randomised Trial[NCT00396513]		0 participants	Interventional	2005-09-30	Recruiting
A Comparison of a Pulse-Based Diet and the Therapeutic Lifestyle Changes Diet on Reproductive and Metabolic Parameters in Women With Polycystic Ovary Syndrome[NCT05428566]		110 participants (Anticipated)	Interventional	2022-01-01	Recruiting
Effect of Metformin on Insulin Sensitivity and Pan-Arterial Vascular Function in Adults With Metabolic Syndrome[NCT02633488]		19 participants (Actual)	Interventional	2014-06-30	Completed
Open-label, Flexible-dose Adjunctive Bromocriptine for Patients With Schizophrenia and Impaired Glucose Tolerance[NCT03575000]	Phase 4	20 participants (Anticipated)	Interventional	2023-11-01	Not yet recruiting
A Multicenter, Prospective, Randomized Study to Assess the Effect of Metformin Supplementation on IVF Outcome and Intrafollicular Environment in Patients With Polycystic Ovarian Syndrome Undergoing In Vitro Fertilization/Embryo Transfer[NCT03086005]	Phase 3	24 participants (Actual)	Interventional	2011-10-12	Completed
A Phase 3b, Double-Blind, Randomized Study to Determine the Efficacy and Safety of Pioglitazone HCl and Metformin HCl Fixed-Dose Combination Therapy Compared to Pioglitazone HCl Monotherapy and to Metformin HCl Monotherapy in the Treatment of Subjects Wit[NCT00727857]	Phase 3	600 participants (Actual)	Interventional	2007-06-30	Completed
DPP-4 Inhibitors in Patients With Type 2 Diabetes and Acute Myocardial Infarction:Effects on Platelet Function[NCT02377388]	Phase 3	74 participants (Actual)	Interventional	2017-02-07	Completed
A Double-blind, Randomized, Placebo-controlled, Parallel Design Study to Evaluate the Effects of the Cardio Formulation on Oxidized LDL in Individuals Who Are Overweight to Mildly Obese and Otherwise Healthy[NCT04317287]		9 participants (Actual)	Interventional	2019-12-10	Terminated (stopped due to COVID-19 Pandemic)
The Effect of Acupuncture on Insulin Sensitivity of Women With Polycystic Ovary Syndrome and Insulin Resistance: a Randomized Controlled Trial[NCT02491333]	Phase 3	342 participants (Actual)	Interventional	2015-08-31	Completed
Effect of Insulin Sensitizer Therapy on Atherothrombotic and Inflammatory Profiles Associated With Insulin Resistance[NCT00443755]	Phase 2	28 participants (Actual)	Interventional	2005-08-31	Completed
Clinical and Biochemical Study of the Effects of Rosuvastatin, Vitamin E, and N-Acetyl Cysteine on Patients With Non-alcoholic Steatohepatitis: a Randomized Controlled Trial[NCT06105060]	Early Phase 1	160 participants (Anticipated)	Interventional	2023-12-17	Not yet recruiting
Markers of Oxidative Stress and Inflammation in Patients With Intestinal Metaplasia and Metabolic Syndrome[NCT02695186]		180 participants (Anticipated)	Observational	2016-02-29	Recruiting
A Retrospective Epidemiological Study to Investigate Outcome and Mortality With Glucose Lowering Drug Treatment in Primary Care[NCT01121315]		58,326 participants (Actual)	Observational	2010-05-31	Completed
A Randomized, Double-Blind, Placebo-Controlled Study of Metformin and Rosiglitazone, Alone or in Combination, in HIV-Infected Subjects With Hyperinsulinemia and Elevated Waist/Hip Ratio[NCT00015691]		105 participants	Interventional		Completed
Use of Metformin in Prevention and Treatment of Cardiac Fibrosis in PAI-1 Deficient Population[NCT05317806]	Phase 4	15 participants (Anticipated)	Interventional	2022-10-10	Active, not recruiting
Clinical Metabolic and Endocrine Parameters in Response to Metformin and Lifestyle Intervention in Women With Polycystic Ovary Syndrome: A Phase 4 Randomized, Double- Blind and Placebo Control Trial[NCT00679679]	Phase 4	30 participants (Actual)	Interventional	2003-01-31	Completed
Efficacy and Safety of Furocyst in Patients With Poly Cystic Ovary Syndrome[NCT02789488]	Phase 4	50 participants (Actual)	Interventional	2013-09-30	Completed
Descriptive, Transversal Study of Evaluation of Cardiovascular Risks Factors and Prevalence of Metabolic Syndrome in the Different Phenotypes of Women With Polycystic Ovary Syndrome[NCT00784615]		80 participants (Anticipated)	Observational	2007-12-31	Recruiting
Anxiety and Sexual Malfunction in Infertile Polycystic Ovarian Syndrome Patients[NCT05056272]		128 participants (Anticipated)	Observational	2022-01-01	Recruiting
The Impact of Continuous Aerobic Exercise and High-Intensity Interval Training on Reproductive Outcomes in Polycystic Ovary Syndrome: A Pilot Randomized Controlled Trial.[NCT03362918]		60 participants (Actual)	Interventional	2018-01-01	Completed
Adipose Tissue Angiogenesis in Polycystic Ovary Syndrome (PCOS)[NCT01745471]		36 participants (Anticipated)	Observational	2012-12-06	Active, not recruiting
The Effects of Contraceptive Pill and Hormonal Vaginal Ring on Hormonal, Inflammatory and Metabolic Parameters in Women of Reproductive Age With Polycystic Ovary Syndrome (PCOS).[NCT01588873]	Phase 4	42 participants (Anticipated)	Interventional	2012-04-30	Recruiting
Physical Activity and Sedentary Behavior Change; Impact on Lifestyle Intervention Effects for Diabetes Translation[NCT02467881]		308 participants (Actual)	Interventional	2015-09-30	Active, not recruiting
Circulating Anti-mullerian Hormone as Predictor of Ovarian Response to Clomiphene Citrate in Women With Polycystic Ovary Syndrome[NCT03316469]		40 participants (Anticipated)	Interventional	2018-07-31	Not yet recruiting
A Phase 3, Randomized, Triple-Blind, Parallel-Group, Long-Term, Placebo-Controlled, Multicenter Study to Examine the Effect on Glucose Control (HbA1c) of AC2993 Given Two Times a Day in Subjects With Type 2 Diabetes Mellitus Treated With Metformin Alone[NCT00039013]	Phase 3	336 participants (Actual)	Interventional	2002-03-31	Completed
An Open Label Study to Examine the Long Term Effect on Glucose Control (HbA1c) and Safety and Tolerability of Exenatide Given Two Times a Day to Subjects With Type 2 Diabetes Mellitus[NCT00111540]	Phase 3	456 participants (Actual)	Interventional	2002-11-30	Completed
Magnetic Resonance Assessment of Victoza Efficacy in the Regression of Cardiovascular Dysfunction In Type 2 Diabetes Mellitus[NCT01761318]	Phase 4	50 participants (Actual)	Interventional	2013-11-30	Completed
Prospective, Parallel Goups Study, Aimed to Evaluating Possible Benefits of the Treatment of New Generation Hypoglycaemic Drugs Compared to Sulphonylureas for the Tratment of Type 2 Diabetes Mellitus[NCT04272359]		138 participants (Anticipated)	Observational [Patient Registry]	2019-05-06	Recruiting
Impact of Rheumatoid Arthritis on Type 2 Diabetes Mellitus[NCT02639988]		1,000 participants (Anticipated)	Observational	2016-04-13	Suspended
Efficacy and Safety of Metformin Glycinate Compared to Metformin Hydrochloride on the Progression of Type 2 Diabetes[NCT04943692]	Phase 3	500 participants (Anticipated)	Interventional	2021-08-31	Suspended (stopped due to Administrative decision of the investigation direction)
Modulation of Insulin Secretion and Insulin Sensitivity in Bangladeshi Type 2 Diabetic Subjects by an Insulin Sensitizer Pioglitazone and T2DM Association With PPARG Gene Polymorphism.[NCT01589445]	Phase 4	77 participants (Actual)	Interventional	2008-11-30	Completed
Pilot Study on the Effects of Fasting Mimicking Diet (FMD) in Women With Polycystic[NCT05196568]		100 participants (Anticipated)	Interventional	2021-07-01	Active, not recruiting
Bioequivalence Study of 2 mg Cyproterone Acetate and 0.035 mg Ethinyl Estradiol in Indonesian Healthy Females[NCT04964193]		24 participants (Actual)	Interventional	2019-03-12	Completed
A Long Term, Open Label, Randomised Study in Patients With Type 2 Diabetes, Comparing the Combination of Rosiglitazone and Either Metformin or Sulfonylurea With Metformin Plus Sulfonylurea on Cardiovascular Endpoints and Glycaemia[NCT00379769]	Phase 3	4,447 participants (Actual)	Interventional	2001-04-30	Completed
Characterization of the Cardiotoxic Effects of Chemotherapies With Anthracyclines and Trastuzumab for Breast Cancer by Contrast-enhanced Cardiovascular Magnetic Resonance Imaging (CMR).[NCT00679874]		66 participants (Anticipated)	Observational	2008-05-31	Terminated (stopped due to No subjects indentifiable)
Rosiglitazone And Fenofibrate Additive Effects on Lipids (RAFAEL)[NCT00819910]	Phase 4	41 participants (Actual)	Interventional	2008-09-30	Terminated (stopped due to Slow recruitment and increase in deployment overseas limiting follow up)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Primary outcome for years 2002-2008 defined according to American Diabetes Association criteria (fasting plasma glucose level >= 126 mg/dL [7.0 mmol/L] or 2-hour plasma glucose >= 200 mg/dL [11.1 mmol/L], after a 75 gram oral glucose tolerance test (OGTT), and confirmed with a repeat test). (NCT00038727)
Timeframe: Outcomes were assessed from 1996-2008 (approximately 12 years including 6 years of DPP).

Mortality

Intervention	diabetes incidence (cases per 100 person (Number)
1 Original Lifestyle	5.3
2 Original Metformin	6.4
3 Original Placebo	7.8

All cause-mortality through clinic reports and National Death Index search (NCT00038727)
Timeframe: Outcomes were assessed throughout follow-up from 1996 to 2022. National Death Index search conducted in 2019 using early release data as of Dec 2018.

Prevalence of Aggregate Microvascular Complication

Intervention	Participants (Count of Participants)
1 Original Lifestyle	158
2 Original Metformin	152
3 Original Placebo	143

Aggregate microvascular disease is defined as the average prevalence of 3 components: (1) retinopathy measured by photography (ETDRS of 20 or greater); (2) neuropathy detected by Semmes Weinstein 10 gram monofilament, and (3) nephropathy based on estimated glomerular filtration rate (eGFR by chronic kidney disease (CKD-Epi) equation ) (<45 ml/min, confirmed) and albumin-to-creatinine ratio in spot urine (> 30mg/gm, confirmed). (NCT00038727)
Timeframe: Outcomes were assessed from 2012-2013 (approximately 2 years).

Subclinical Atherosclerosis

Intervention	average percentage of participants (Number)
1 Original Lifestyle	11.3
2 Original Metformin	13
3 Original Placebo	12.4

Measured using coronary artery calcification (CAC). (NCT00038727)
Timeframe: Outcomes were assessed from 2012-2013 (approximately 2 years).

Andersen-Gill Model for All Cardiovascular Death (CV Death) or Hospitalizations for Heart Failure (HFF) (On-Study Approach) (Overall Cardiovascular Study)

Intervention	CAC geometric mean in AU (Geometric Mean)
	Men	Women
1 Original Lifestyle	70.1	6.0
2 Original Metformin	40.2	6.1
3 Original Placebo	63.7	5.3

All events (first and recurrent) of the composite of CV death and HHF were assessed using an Andersen-Gill model. Person-years were calculated as the sum of time from randomization to end of follow-up. The on-study approach included events that occurred between the randomization date and the on-study censor date. (NCT01986881)
Timeframe: Up to approximately 6 years

Andersen-Gill Model for Total MACE (On-Study Approach) (Overall Cardiovascular Study)

Intervention	Events per 100 Person-years (Number)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	2.92
Ertugliflozin 15 mg (Overall Cardiovascular Study)	2.71
Placebo (Overall Cardiovascular Study)	3.42
All Ertugliflozin (Overall Cardiovascular Study)	2.82

All events (first and recurrent) of the composite of MACE (3-point major adverse cardiovascular events: cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)), non-fatal MI, and non-fatal stroke) were assessed using Andersen-Gill model. The on-study approach included events that occurred between the randomization date and the on-study censor date. (NCT01986881)
Timeframe: Up to approximately 6 years

Baseline Hemoglobin A1C (A1C) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

Intervention	Events per 100 Person-years (Number)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	4.35
Ertugliflozin 15 mg (Overall Cardiovascular Study)	4.91
Placebo (Overall Cardiovascular Study)	4.59
All Ertugliflozin (Overall Cardiovascular Study)	4.63

Baseline Hemoglobin A1C (A1C) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

Intervention	A1C Percentage (Mean)
Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	8.45
Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	8.38
Placebo (Ins+/-Met Sub-study)	8.39

Baseline Hemoglobin A1C (A1C) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

Intervention	A1C Percentage (Mean)
Ertugliflozin 5 mg (Metformin With Sulfonylurea Glycemic Sub-study)	8.39
Ertugliflozin 15 mg (Metformin With Sulfonylurea Glycemic Sub-study)	8.30
Placebo (Metformin With Sulfonylurea Glycemic Sub-study)	8.27

Baseline Insulin Dose for Participants Receiving Insulin at Baseline - (Insulin With or Without Metformin Add-on Glycemic Sub-study)

Baseline Insulin Dose for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

Baseline Serum Creatinine (Overall Cardiovascular Study)

Baseline Urinary Albumin/Creatinine Ratio (Overall Cardiovascular Study)

Intervention	A1C Percentage (Mean)
Ertugliflozin 5 mg (Sulfonylurea Monotherapy Glycemic Sub-Study)	8.27
Ertugliflozin 15 mg (Sulfonylurea Monotherapy Glycemic Sub-Study)	8.39
Placebo (Sulfonylurea Monotherapy Glycemic Sub-Study)	8.21

Intervention	Unit/day (Mean)
Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	70.76
Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	67.29
Placebo (Insulin +/- Metformin Glycemic Sub-study)	73.20

Intervention	Units/Day (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	63.82
Ertugliflozin 15 mg (Overall Cardiovascular Study)	62.15
Placebo (Overall Cardiovascular Study)	65.74

Intervention	mg/dL (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	0.992
Ertugliflozin 15 mg (Overall Cardiovascular Study)	0.985
Placebo (Overall Cardiovascular Study)	0.991
All Ertugliflozin (Overall Cardiovascular Study)	0.998

Baseline reflects Week 0 albumin/creatinine ratio. (NCT01986881)
Timeframe: Baseline

Change From Baseline at Week 18 in Insulin Dose for Participants Receiving Insulin at Baseline - Including Rescue Approach (Insulin With or Without Metformin Add-on Glycemic Sub-study)

Intervention	mg/g (Median)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	18.00
Ertugliflozin 15 mg (Overall Cardiovascular Study)	19.00
Placebo (Overall Cardiovascular Study)	19.00

"This change from baseline reflects the Week 18 insulin dose minus the Week 0 insulin dose. A negative number indicates a decrease in insulin dose. Participants who met glycemic rescue criteria received glycemic rescue medication. Including rescue, included data following the initiation of rescue therapy." (NCT01986881)
Timeframe: Baseline and Week 18

Change From Baseline in A1C at Month 24 (Overall Cardiovascular Study)

Intervention	Unit/day (Mean)
Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	-0.71
Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	-2.14
Placebo (Insulin +/- Metformin Glycemic Sub-study)	-0.29

A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 24 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 24

Change From Baseline in A1C at Month 36 (Overall Cardiovascular Study)

Intervention	A1C Percentage (Least Squares Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-0.48
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-0.46
Placebo (Overall Cardiovascular Study)	-0.08

A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 36 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 36

Change From Baseline in A1C at Month 48 (Overall Cardiovascular Study)

Intervention	A1C Percentage (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-0.42
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-0.38
Placebo (Overall Cardiovascular Study)	-0.04

A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 48 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 48

Change From Baseline in A1C at Month 60 (Overall Cardiovascular Study)

Intervention	A1C Percentage (Least Squares Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-0.22
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-0.17
Placebo (Overall Cardiovascular Study)	0.14

A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 60 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 60

Change From Baseline in A1C at Month 72 (Overall Cardiovascular Study)

Intervention	A1C Percentage (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-0.25
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-0.28
Placebo (Overall Cardiovascular Study)	-0.10

A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Month 72 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 72

Change From Baseline in A1C at Week 52 (Overall Cardiovascular Study)

Intervention	A1C Percentage (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-0.35
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-0.13
Placebo (Overall Cardiovascular Study)	0.24

A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 52 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Week 52

Change From Baseline in Body Weight at Month 24 (Overall Cardiovascular Study)

Intervention	A1C Percentage (Least Squares Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-0.69
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-0.67
Placebo (Overall Cardiovascular Study)	-0.19

This change from baseline reflects the Month 24 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 24

Change From Baseline in Body Weight at Month 36 (Overall Cardiovascular Study)

Intervention	Kilograms (Least Squares Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-2.75
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-3.17
Placebo (Overall Cardiovascular Study)	-0.65

This change from baseline reflects the Month 36 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 36

Change From Baseline in Body Weight at Month 48 (Overall Cardiovascular Study)

Intervention	Kilograms (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-3.03
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-3.41
Placebo (Overall Cardiovascular Study)	-0.98

This change from baseline reflects the Month 48 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 48

Change From Baseline in Body Weight at Month 60 (Overall Cardiovascular Study)

Intervention	Kilograms (Least Squares Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-3.39
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-3.83
Placebo (Overall Cardiovascular Study)	-1.29

This change from baseline reflects the Month 60 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 60

Change From Baseline in Body Weight at Month 72 (Overall Cardiovascular Study)

Intervention	Kilograms (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-3.66
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-4.58
Placebo (Overall Cardiovascular Study)	-1.21

This change from baseline reflects the Month 72 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 72

Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

Intervention	Kilograms (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-4.18
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-7.37
Placebo (Overall Cardiovascular Study)	-0.98

"This change from baseline reflects the Week 18 body weight minus the Week 0 body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. Excluding Rescue excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy." (NCT01986881)
Timeframe: Baseline and Week 18

Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

Intervention	Kilograms (Least Squares Mean)
Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	-1.87
Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	-2.13
Placebo (Insulin +/- Metformin Glycemic Sub-study)	-0.25

"This change from baseline reflects the Week 18 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. Excluding Rescue excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy." (NCT01986881)
Timeframe: Baseline and Week 18

Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)

Intervention	Kilograms (Least Squares Mean)
Ertugliflozin 5 mg (Metformin With Sulfonylurea Glycemic Sub-study)	-2.04
Ertugliflozin 15 mg (Metformin With Sulfonylurea Glycemic Sub-study)	-2.41
Placebo (Metformin With Sulfonylurea Glycemic Sub-study)	-0.47

Change From Baseline in Body Weight at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

Intervention	Kilograms (Least Squares Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-2.03
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-2.32
Placebo (Overall Cardiovascular Study)	-0.40

Change From Baseline in Body Weight at Week 52 (Overall Cardiovascular Study)

Intervention	Kilograms (Least Squares Mean)
Ertugliflozin 5 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	-1.75
Ertugliflozin 15 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	-1.20
Placebo (Sulfonylurea Monotherapy Glycemic Sub-study)	-0.68

This change from baseline reflects the Week 52 body weight minus the Week 0 body weight. A negative number indicates a reduction in body weight. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Week 52

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 24 (Overall Cardiovascular Study)

Intervention	Kilograms (Least Squares Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-2.46
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-2.84
Placebo (Overall Cardiovascular Study)	-0.39

This change from baseline reflects the Month 24 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level. (NCT01986881)
Timeframe: Baseline and Month 24

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 36 (Overall Cardiovascular Study)

Intervention	mL/min/1.73 m^2 (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-1.48
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-2.35
Placebo (Overall Cardiovascular Study)	-2.60

This change from baseline reflects the Month 36 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level. (NCT01986881)
Timeframe: Baseline and Month 36

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 48 (Overall Cardiovascular Study)

Intervention	mL/min/1.73 m^2 (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-2.4
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-2.3
Placebo (Overall Cardiovascular Study)	-3.8

This change from baseline reflects the Month 48 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in eGFR level. (NCT01986881)
Timeframe: Baseline and Month 48

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 60 (Overall Cardiovascular Study)

Intervention	mL/min/1.73 m^2 (Least Squares Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-2.75
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-2.93
Placebo (Overall Cardiovascular Study)	-4.41

This change from baseline reflects the Month 60 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level. (NCT01986881)
Timeframe: Baseline and Month 60

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Month 72 (Overall Cardiovascular Study)

Intervention	mL/min/1.73 m^2 (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-2.4
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-2.9
Placebo (Overall Cardiovascular Study)	-6.8

This change from baseline reflects the Month 72 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level. (NCT01986881)
Timeframe: Baseline and Month 72

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 18 (Overall Cardiovascular Study)

Intervention	mL/min/1.73 m^2 (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	3.7
Ertugliflozin 15 mg (Overall Cardiovascular Study)	0.2
Placebo (Overall Cardiovascular Study)	-1.8

This change from baseline reflects the Week 18 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in the eGFR level. (NCT01986881)
Timeframe: Baseline and Week 18

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52 (Overall Cardiovascular Study)

Intervention	mL/min/1.73 m^2 (Least Squares Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-1.22
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-1.81
Placebo (Overall Cardiovascular Study)	-0.03

This change from baseline reflects the Week 52 eGFR minus the Week 0 eGFR. A negative number indicates a reduction in eGFR level. (NCT01986881)
Timeframe: Baseline and Week 52

Change From Baseline in Fasting Plasma Glucose (FPG) at Month 24 (Overall Cardiovascular Study)

Intervention	mL/min/1.73 m^2 (Least Squares Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-0.51
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-1.18
Placebo (Overall Cardiovascular Study)	-0.30

FPG was analyzed after an overnight fast. This change from baseline reflects the Month 24 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 24

Change From Baseline in Fasting Plasma Glucose (FPG) at Month 36 (Overall Cardiovascular Study)

Intervention	mg/dL (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-22.09
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-24.31
Placebo (Overall Cardiovascular Study)	-4.39

FPG was analyzed after an overnight fast. This change from baseline reflects the Month 36 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 36

Change From Baseline in Fasting Plasma Glucose (FPG) at Month 48 (Overall Cardiovascular Study)

Intervention	mg/dL (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-19.39
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-22.59
Placebo (Overall Cardiovascular Study)	-3.63

FPG was analyzed after an overnight fast. This change from baseline reflects the Month 48 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 48

Change From Baseline in Fasting Plasma Glucose (FPG) at Month 60 (Overall Cardiovascular Study)

Intervention	mg/dL (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-15.28
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-16.16
Placebo (Overall Cardiovascular Study)	3.59

FPG was analyzed after an overnight fast. This change from baseline reflects the Month 60 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 60

Change From Baseline in Fasting Plasma Glucose (FPG) at Month 72 (Overall Cardiovascular Study)

Intervention	mg/dL (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-13.87
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-11.15
Placebo (Overall Cardiovascular Study)	-4.69

FPG was analyzed after an overnight fast. This change from baseline reflects the Month 72 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 72

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

Intervention	mg/dL (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-2.46
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-84.83
Placebo (Overall Cardiovascular Study)	14.56

"FPG was analyzed after an overnight fast. This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. A negative number indicates a reduction in the FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. Excluding Rescue excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy." (NCT01986881)
Timeframe: Baseline and Week 18

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

Intervention	mg/dL (Least Squares Mean)
Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	-26.98
Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	-33.15
Placebo (Insulin +/- Metformin Glycemic Sub-study)	-7.74

"FPG was analyzed after an overnight fast. This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. Excluding Rescue excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy." (NCT01986881)
Timeframe: Baseline and Week 18

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)

Intervention	mg/dL (Least Squares Mean)
Ertugliflozin 5 mg (Metformin With Sulfonylurea Glycemic Sub-study)	-35.28
Ertugliflozin 15 mg (Metformin With Sulfonylurea Glycemic Sub-study)	-36.18
Placebo (Metformin With Sulfonylurea Glycemic Sub-study)	-4.81

"FPG was analyzed after an overnight fast. This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. Excluding rescue, excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy." (NCT01986881)
Timeframe: Baseline and Week 18

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

Intervention	mg/dL (Least Squares Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-32.18
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-34.64
Placebo (Overall Cardiovascular Study)	-17.08

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 (Overall Cardiovascular Study)

Intervention	mg/dL (Least Squares Mean)
Ertugliflozin 5 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	-28.28
Ertugliflozin 15 mg (Sulfonylurea Monotherapy Glycemic Sub-study)	-26.97
Placebo (Sulfonylurea Monotherapy Glycemic Sub-study)	-14.76

FPG was analyzed after an overnight fast. This change from baseline reflects the Week 52 FPG minus the Week 0 FPG. A negative number indicates a reduction in FPG. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Week 52

Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Insulin With or Without Metformin Add-on Glycemic Sub-study)

"A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 18 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received glycemic rescue medication. Excluding Rescue excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy." (NCT01986881)
Timeframe: Baseline and Week 18

Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Overall Cardiovascular Study)

Change From Baseline in Hemoglobin A1C (A1C) at Week 18 - Excluding Rescue Approach (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

Change From Baseline in Insulin Dose at Month 24 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

This change from baseline reflects the Month 24 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose. (NCT01986881)
Timeframe: Baseline and Month 24

Change From Baseline in Insulin Dose at Month 36 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

This change from baseline reflects the Month 36 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose. (NCT01986881)
Timeframe: Baseline and Month 36

Change From Baseline in Insulin Dose at Month 48 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

This change from baseline reflects the Month 48 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose. (NCT01986881)
Timeframe: Baseline and Month 48

Change From Baseline in Insulin Dose at Month 60 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

This change from baseline reflects the Month 60 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose. (NCT01986881)
Timeframe: Baseline and Month 60

Change From Baseline in Insulin Dose at Week 18 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

This change from baseline reflects the Week 18 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose. (NCT01986881)
Timeframe: Baseline and Week 18

Change From Baseline in Insulin Dose at Week 52 for Participants Who Were on Insulin at Baseline (Overall Cardiovascular Study)

This change from baseline reflects the Week 52 insulin dose minus the Week 0 insulin dose. A negative number indicates a reduction in the insulin dose. (NCT01986881)
Timeframe: Baseline and Week 52

Change From Baseline in Serum Creatinine at Month 24 (Overall Cardiovascular Study)

This change from baseline reflects the Month 24 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 24

Change From Baseline in Serum Creatinine at Month 36 (Overall Cardiovascular Study)

This change from baseline reflects the Month 36 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 36

Change From Baseline in Serum Creatinine at Month 48 (Overall Cardiovascular Study)

This change from baseline reflects the Month 48 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 48

Change From Baseline in Serum Creatinine at Month 60 (Overall Cardiovascular Study)

This change from baseline reflects the Month 60 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 60

Change From Baseline in Serum Creatinine at Month 72 (Overall Cardiovascular Study)

This change from baseline reflects the Month 72 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 72

Change From Baseline in Serum Creatinine at Week 18 (Overall Cardiovascular Study)

This change from baseline reflects the Week 18 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Week 18

Change From Baseline in Serum Creatinine at Week 52 (Overall Cardiovascular Study)

This change from baseline reflects the Week 52 serum creatinine minus the Week 0 serum creatinine. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Week 52

Change From Baseline in Sitting Diastolic Blood (DBP) Pressure at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

"This change from baseline reflects the Week 18 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. Excluding Rescue excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy." (NCT01986881)
Timeframe: Baseline and Week 18

Change From Baseline in Sitting Diastolic Blood (DBP) Pressure at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 24 (Overall Cardiovascular Study)

This change from baseline reflects the Month 24 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 24

Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 36 (Overall Cardiovascular Study)

This change from baseline reflects the Month 36 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 36

Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 48 (Overall Cardiovascular Study)

This change from baseline reflects the Month 48 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 48

Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 60 (Overall Cardiovascular Study)

This change from baseline reflects the Month 60 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 60

Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Month 72 (Overall Cardiovascular Study)

This change from baseline reflects the Month 72 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 72

Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

"This change from baseline reflects the Week 18 DBP minus the Week 0 BBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. Excluding Rescue excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy." (NCT01986881)
Timeframe: Baseline and Week 18

Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)

"This change from baseline reflects the Week 18 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. Excluding rescue, excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy." (NCT01986881)
Timeframe: Baseline and Week 18

Change From Baseline in Sitting Diastolic Blood Pressure (DBP) at Week 52 (Overall Cardiovascular Study)

This change from baseline reflects the Week 52 DBP minus the Week 0 DBP. A negative number indicates a reduction in DBP. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Week 52

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 24 (Overall Cardiovascular Study)

This change from baseline reflects the Month 24 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 24

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 36 (Overall Cardiovascular Study)

This change from baseline reflects the Month 36 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 36

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 48 (Overall Cardiovascular Study)

This change from baseline reflects the Month 48 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 48

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 60 (Overall Cardiovascular Study)

This change from baseline reflects the Month 60 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 60

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Month 72 (Overall Cardiovascular Study)

This change from baseline reflects the Month 72 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 72

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

"This change from baseline reflects the Week 18 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. Excluding Rescue excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy." (NCT01986881)
Timeframe: Baseline and Week 18

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Overall Cardiovascular Study)

"This change from baseline reflects the Week 18 SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. Excluding rescue, excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy." (NCT01986881)
Timeframe: Baseline and Week 18

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 52 (Overall Cardiovascular Study)

This change from baseline reflects the Week 52 sitting SBP minus the Week 0 SBP. A negative number indicates a reduction in SBP. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Week 52

Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 24 (Overall Cardiovascular Study)

This percent change relative to baseline reflects the Month 24 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in urinary albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 24

Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 36 (Overall Cardiovascular Study)

This percent change relative to baseline reflects the Month 36 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in urinary albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 36

Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 48 (Overall Cardiovascular Study)

This percent change relative to baseline reflects the Month 48 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 48

Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Month 60 (Overall Cardiovascular Study)

This percent change relative to baseline reflects the Month 60 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Month 60

Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Week 18 (Overall Cardiovascular Study)

This percent change relative to baseline reflects the Week 18 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in the urinary albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Week 18

Percent Change From Baseline in Urinary Albumin/Creatinine Ratio at Week 52 (Overall Cardiovascular Study)

This percent change relative to baseline reflects the Week 52 albumin/creatinine ratio minus the Week 0 albumin/creatinine ratio. This difference was divided by the baseline to obtain the percent change. A negative number indicates a reduction in the albumin/creatinine ratio. Participants who met glycemic rescue criteria received glycemic rescue medication. (NCT01986881)
Timeframe: Baseline and Week 52

Percentage of Participants Discontinuing Study Treatment Due to An AE (Insulin With or Without Metformin Add-on Glycemic Sub-study)

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. (NCT01986881)
Timeframe: Up to 18 weeks

Percentage of Participants Discontinuing Study Treatment Due to An AE (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

Percentage of Participants Discontinuing Study Treatment Due to An AE (Overall Cardiovascular Study)

Percentage of Participants Discontinuing Study Treatment Due to An AE (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

Percentage of Participants Experiencing an Adverse Event (AE) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

Percentage of Participants Experiencing an Adverse Event (AE) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

Percentage of Participants Experiencing an Adverse Event (AE) (Overall Cardiovascular Study)

Percentage of Participants Experiencing an Adverse Event (AE) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 24 (Overall Cardiovascular Study)

Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 36 (Overall Cardiovascular Study)

Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 48 (Overall Cardiovascular Study)

Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Month 60 (Overall Cardiovascular Study)

Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Week 18 (Overall Cardiovascular Study)

Percentage of Participants With an A1C <6.5% (<48 mmol/Mol) at Week 52 (Overall Cardiovascular Study)

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 24 (Overall Cardiovascular Study)

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 36 (Overall Cardiovascular Study)

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 48 (Overall Cardiovascular Study)

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Month 60 (Overall Cardiovascular Study)

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Excluding Rescue Approach) (Insulin With or Without Metformin Add-on Glycemic Sub-study)

"A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication. Excluding Rescue excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy." (NCT01986881)
Timeframe: Week 18

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Excluding Rescue Approach) (Metformin With Sulfonylurea Add-on Glycemic Sub-study)

"A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication. Excluding Rescue excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy." (NCT01986881)
Timeframe: Week 18

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Excluding Rescue Approach) (Sulfonylurea Monotherapy Add-on Glycemic Sub-Study)

"A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. Participants who met glycemic rescue criteria received glycemic rescue medication. Excluding Rescue excluded all data following the initiation of rescue in order to avoid the confounding influence of the rescue therapy." (NCT01986881)
Timeframe: Week 18

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 18 (Overall Cardiovascular Study)

Percentage of Participants With an A1C <7% (<53 mmol/Mol) at Week 52 (Overall Cardiovascular Study)

Time to First Occurrence of Fatal or Non-fatal Myocardial Infarction (On-Study Approach) (Overall Cardiovascular Study)

Time to First Occurrence of Fatal or Non-fatal Myocardial Infarction. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). (NCT01986881)
Timeframe: Up to approximately 6 years

Time to First Occurrence of Fatal or Non-fatal Stroke (FNF Stroke) (On-Study Approach) (Overall Cardiovascular Study)

Time to the first occurrence of fatal and no-fatal stroke. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). The on-study approach included events that occurred between the randomization date and the on-study censor date. (NCT01986881)
Timeframe: Up to approximately 6 years

Time to First Occurrence of Hospitalization for Heart Failure (HHF) (On-Study Approach) (Overall Cardiovascular Study)

Time to the first occurrence of heart failure requiring hospitalization (adjudicated). The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). The on-study approach included events that occurred between the randomization date and the on-study censor date. (NCT01986881)
Timeframe: Up to approximately 6 years

Time to First Occurrence of MACE (Composite Endpoint of Major Adverse Cardiovascular Events [Cardiovascular Death, Non-fatal Myocardial Infarction or Non-fatal Stroke]) (On-Treatment + 365-day Approach) (Overall Cardiovascular Study)

Time to the first occurrence of any of the following adjudicated components of the primary composite endpoint (3-point major adverse cardiovascular events (MACE)): cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)), non-fatal MI, and non-fatal stroke. The on-treatment approach included confirmed events that occurred between the date of first dose of study medication and the on-treatment censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, last contact date, or 365 days after the last dose). (NCT01986881)
Timeframe: Up to approximately 6 years

Time to First Occurrence of MACE Plus (Composite Endpoint of Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke or Hospitalization for Unstable Angina) (On-Study Approach) (Overall Cardiovascular Study)

Time to the first occurrence of any of the following adjudicated components 4-point MACE: cardiovascular death (including fatal stroke and fatal myocardial infarction), non-fatal myocardial infarction, non-fatal stroke, and hospitalization for unstable angina pectoris. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). The on-study approach included events that occurred between the randomization date and the on-study censor date. (NCT01986881)
Timeframe: Up to approximately 6 years

Time to First Occurrence of the Renal Composite: the Composite of Renal Death, Renal Dialysis/Transplant, or Doubling of Serum Creatinine From Baseline (On-Study Approach) (Overall Cardiovascular Study)

Renal composite endpoint was defined as a composite of renal death, renal dialysis/transplant, or doubling of serum creatinine from baseline. The on-study approach included events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to first event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). The on-study approach included events that occurred between the randomization date and the on-study censor date. (NCT01986881)
Timeframe: Up to approximately 6 years

Time to Initiation of Insulin for Participants Not on Insulin at Baseline (Overall Cardiovascular Study)

Participants who were not on insulin therapy at the start of study medication. (NCT01986881)
Timeframe: Up to approximately 6 years

Time to Occurrence of Cardiovascular (CV) Death or Hospitalization for Heart Failure (HHF) (On-Study Approach) (Overall Cardiovascular Study)

Time to the occurrence of any of the following adjudicated components of cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)) or hospitalization for heart failure. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to event or time to censoring (the earliest of participants' end of study date, death date, or last contact date). (NCT01986881)
Timeframe: Up to approximately 6 years

Time to Occurrence of Cardiovascular Death (On-study Approach) (Overall Cardiovascular Study)

Time to the occurrence of cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)). The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to CV death or time to censoring (the earliest of participants' end of study date or date last known to be alive). (NCT01986881)
Timeframe: Up to approximately 6 years

Time to Occurrence of Death From Any Cause (On-Study Approach) (Overall Cardiovascular Study)

Time to the occurrence of death from any cause. The on-study approach included confirmed events that occurred between the randomization date and the on-study censor date. Person-years was calculated as the sum of participants' time to event or time to censoring (the earliest of participants' end of study date, death date, last contact date, or date last known to be alive. The on-study approach included events that occurred between the randomization date and the on-study censor date. (NCT01986881)
Timeframe: Up to approximately 6 years

Time to the First Occurrence of a Participant Receiving Glycemic Rescue Therapy Through Week 18 (Overall Cardiovascular Study)

Participants who met glycemic rescue criteria received open-label sitagliptin glycemic rescue medication. (NCT01986881)
Timeframe: Up to 18 weeks

Percentage of Participants With Albuminuria Progression or Regression at Month 24 (Overall Cardiovascular Study)

Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g). (NCT01986881)
Timeframe: Month 24

Percentage of Participants With Albuminuria Progression or Regression at Month 36 (Overall Cardiovascular Study)

Percentage of Participants With Albuminuria Progression or Regression at Month 48 (Overall Cardiovascular Study)

Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline and normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g). (NCT01986881)
Timeframe: Month 48

Percentage of Participants With Albuminuria Progression or Regression at Month 60 (Overall Cardiovascular Study)

Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal albuminuria at baseline to micro albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g). (NCT01986881)
Timeframe: Month 60

Percentage of Participants With Albuminuria Progression or Regression at Week 18 (Overall Cardiovascular Study)

Albuminuria progression and regression were assessed relative to the baseline albuminuria category. Progression was defined as either a change from having normal-albuminuria at baseline to micro-albuminuria at the respective visit, or micro-albuminuria at baseline to macro-albuminuria at the respective visit, or normal albuminuria at baseline to macro-albuminuria at the respective visit. Regression was defined as either a change from having micro-albuminuria at baseline to normal albuminuria at the respective visit, or macro-albuminuria at baseline to micro-albuminuria at the respective visit, or macro-albuminuria at baseline to normal albuminuria at the respective visit. Normal albuminuria: urine albumin to urinary creatinine ratio (UACR) <30 (mg/g); Micro-albuminuria: UACR ≥30 and ≤300 (mg/g); Macro-albuminuria: UACR>300 (mg/g). (NCT01986881)
Timeframe: Week 18

Percentage of Participants With Albuminuria Progression or Regression at Week 52 (Overall Cardiovascular Study)

Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Body Weight

Estimated mean change from baseline to last assessment in body weight in the trial during the treatment period. (NCT01720446)
Timeframe: Week 0, up to week 104

Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Fasting Plasma Glucose

Estimated mean change from baseline to last assessment in fasting plasma glucose in the trial during the treatment period. (NCT01720446)
Timeframe: Week 0, up to week 104

Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Glycosylated Haemoglobin (HbA1c)

Estimated mean change from baseline in glycosylated haemoglobin (HbA1c) to last assessment in the trial during the treatment period. (NCT01720446)
Timeframe: Week 0, up to week 104

Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Lipid Profile (Free Fatty Acids)

Estimated ratio to baseline at week 104 during the treatment period in lipid profile (free fatty acids). (NCT01720446)
Timeframe: Week 0, up to week 104

Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Urinary Albumin to Creatinine Ratio

Estimated ratio to baseline in urinary albumin to creatinine ratio at week 104 during the treatment period. (NCT01720446)
Timeframe: Week 0, up to week 104

Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Vital Signs (Pulse Rate)

Estimated mean change from baseline to last assessment in the trial during the treatment period in vital signs (pulse rate). (NCT01720446)
Timeframe: Week 0, up to week 104

Incidence During the Trial in Other Treatment Outcomes: Adverse Events

Rates (event rate per 100 years of exposure) of treatment emergent adverse events. (NCT01720446)
Timeframe: Weeks 0-109

Incidence During the Trial in Other Treatment Outcomes: Hypoglycaemic Events

Rates (event rate per 100 exposure years) of severe or blood glucose confirmed symptomatic hypoglycaemia defned as an episode that was severe according to the American diabetic association (ADA) classification or blood glucose (BG) confirmed by a PG value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. (NCT01720446)
Timeframe: Week 0 - 109

Occurrence During the Trial in Other Treatment Outcomes: Anti-semaglutide Antibodies

The percentage of subjects that tested positive for anti-semaglutide antibodies at any time point post-baseline during the trial, from week 0 to week 109. (NCT01720446)
Timeframe: Weeks 0-109

Time From Randomisation to First Occurrence of a MACE, Defined as Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke

Percentage of subjects experiencing a first event of a major adverse cardiovascular event (MACE), defined as cardiovascular (CV) death, non-fatal myocardial infarction (MI), or non-fatal stroke. (NCT01720446)
Timeframe: Time from randomisation up to end of follow-up (scheduled at week 109)

Time From Randomisation to First Occurrence of All-cause Death, Non-fatal MI, or Non-fatal Stroke

Percentage of subjects experiencing a first occurrence of all-cause death, non-fatal MI, or non-fatal stroke. (NCT01720446)
Timeframe: Time from randomisation up to end of follow-up (scheduled at week 109)

Time From Randomisation to First Occurrence of an Expanded Composite Cardiovascular Outcome

Percentage of subjects experiencing first occurrence of an expanded composite CV outcome (defined as either MACE, revascularisation [coronary and peripheral], unstable angina requiring hospitalisation or hospitalisation for heart failure) (NCT01720446)
Timeframe: Time from randomisation up to end of follow-up (scheduled at week 109)

Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Lipid Profile

Estimated ratio to baseline at week 104 during the treatment period in lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides). (NCT01720446)
Timeframe: Week 0, up to week 104

Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Patient Reported Outcome (PRO)

Estimated mean change from baseline to last assessment in the trial in patient reported outcomes (PRO). PRO questionnaire (SF-36v2TM) measured the individual overall health related quality of life namely bodily pain, general health, mental component summary, mental health, physical component summary, physical functioning, role-emotional, role-physical, social functioning and vitality. The PRO scores were transformed to a 0-100 scale with higher scores indicating greater health related quality of life. (NCT01720446)
Timeframe: Week 0, up to week 104

Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Vital Signs

Estimated mean change from baseline to last assessment in the trial during the treatment period in vital signs (diastolic blood pressure and systolic blood pressure). (NCT01720446)
Timeframe: Week 0, up to week 104

Time From Randomisation to Each Individual Component of the Expanded Composite Cardiovascular Outcome

Percentage of subjects experiencing an event onset for each individual component of the expanded composite cardiovascular outcomes (defined as either MACE, revascularisation [coronary and peripheral], unstable angina requiring hospitalisation or hospitalisation for heart failure). (NCT01720446)
Timeframe: Time from randomisation up to end of follow-up (scheduled at week 109)

Change in Body Weight

Change from baseline (week 0) in body weight measured at the end of treatment visit (week 83) is reported. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Week 0, End of treatment

Change in Glycosylated Haemoglobin (HbA1c)

Change from baseline (week 0) in HbA1c measured at the end of treatment visit (week 83) is reported. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Week 0, End of treatment

Change in HDL-cholesterol - Ratio to Baseline

Change from baseline (week 0) in HDL cholesterol (mmol/L) at end of treatment visit (week 83) is presented as ratio to baseline. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Week 0, End of treatment

Change in LDL-cholesterol - Ratio to Baseline

Change from baseline (week 0) in LDL cholesterol (mmol/L) at end of treatment visit (week 83) is presented as ratio to baseline. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Week 0, End of treatment

Change in Pulse Rate

Change from baseline (week 0) in pulse rate measured at the end of treatment visit (week 83) is reported. Results are based on the on-treatment observation period which started at the date of first dose on trial product, ended on last date on trial product +38 days (ascertainment window). (NCT02692716)
Timeframe: Week 0, End of treatment

Change in Total Cholesterol - Ratio to Baseline

Change from baseline (week 0) in total cholesterol (mmol/L) at the end of treatment (week 83) visit is presented as ratio to baseline. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Week 0, End of treatment

Change in Triglycerides - Ratio to Baseline

Change from baseline (week 0) in triglycerides (mmol/L) at end of treatment visit (week 83) is presented as ratio to baseline. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Week 0, End of treatment

Number of Serious Adverse Events

Number of serious adverse events were recorded from week 0 to week 87 in the study. Results are based on the on-treatment observation period which started at the date of first dose on trial product and ended on last date on trial product +38 days (ascertainment window). (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is expected to be no longer than 19 months + 38 days of ascertainment window.

Time From Randomisation to All-cause Death

Number of all-cause deaths in the study are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is expected to be no longer than 19 months + 5 weeks of follow-up period.

Time From Randomisation to First Occurrence of a Composite Endpoint Consisting of: All-cause Death, Non-fatal Myocardial Infarction or Nonfatal Stroke

Participants experiencing first occurrence of a composite CV endpoint (defined as all-cause death, non-fatal myocardial infarction or nonfatal stroke) are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period.

Time From Randomisation to First Occurrence of a Major Adverse Cardiovascular Event (MACE) Composite Endpoint Consisting of: Cardiovascular Death, Non-fatal Myocardial Infarction or Non-fatal Stroke

Number of participants experiencing a first event of a MACE, defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period.

Time From Randomisation to First Occurrence of an Expanded Composite Cardiovascular Endpoint Consisting of: Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke, UAP Requiring Hospitalisation or Hospitalisation for Heart Failure

Participants experiencing first occurrence of an expanded composite CV endpoint [defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, UAP (unstable angina pectoris) requiring hospitalisation or heart failure requiring hospitalisation] are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period.

Time From Randomisation to First Occurrence of Fatal or Non-fatal Myocardial Infarction

Number of participants experiencing a first event of a fatal or non-fatal myocardial infarction are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period.

Time From Randomisation to First Occurrence of Fatal or Non-fatal Stroke

Number of participants experiencing a first event of a fatal or non-fatal stroke are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period.

Time to First AE Leading to Permanent Trial Product Discontinuation

Number of participants who permanently discontinued trial product in ths study are presented. Results are based on the on-treatment observation period which starts at the date of first dose on trial product; ends on last date on trial product +38 days (ascertainment window). (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is expected to be no longer than 19 months + 38 days of ascertainment window.

Change in Eye Examination Category

Participants with eye examination findings, normal, abnormal non clinically significant (NCS) and abnormal clinically significant (CS) at baseline (week -3) and end of treatment visit (week 83) are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Week -3, End of treatment

Change in Systolic and Diastolic Blood Pressure

Change from baseline (week 0) in systolic and diastolic blood pressure measured at the end of treatment visit (week 83) is reported. Results are based on the on-treatment observation period which started at the date of first dose on trial product, ended on last date on trial product +38 days (ascertainment window). (NCT02692716)
Timeframe: Week 0, End of treatment

Time From Randomisation to First Occurrence of Each of the Individual Components in the Expanded Composite Cardiovascular Endpoint

Participants experiencing an event onset for each individual component of the expanded composite cardiovascular outcomes (defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, unstable angina requiring hospitalisation or heart failure requiring hospitalisation) are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period.

Adjusted Change From Baseline in Femoral Neck (FN) Infero-anterior Cortical Thickness Via QCT at Week 76 + 30 Days

Cortical thickness was measured by QCT. Change was calculated as thickness at Week 76 + 30 days minus thickness at Baseline. (NCT00679939)
Timeframe: Baseline and Week 76 + 30 days

Adjusted Change From Baseline in Femoral Neck (FN) Infero-anterior Cortical vBMD Via QCT at Week 76 + 30 Days

vBMD was measured by QCT. Change from Baseline at Week 76 + 30 days was calculated as vBMD at Week 76 + 30 days minus vBMD at baseline and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Infero-anterior is the lower and front section of the FN. (NCT00679939)
Timeframe: Baseline and Week 76 + 30 days

Adjusted Change From Baseline in Femoral Neck (FN) Infero-posterior Cortical Thickness Via QCT at Week 76 + 30 Days

Cortical thickness was measured by QCT. Change from Baseline was calculated as thickness at Week 76 + 30 days minus thickness at Baseline. (NCT00679939)
Timeframe: Baseline and Week 76 + 30 days

Adjusted Change From Baseline in Femoral Neck (FN) Infero-posterior Cortical vBMD Via QCT at Week 76 + 30 Days

vBMD was measured by QCT. Change from Baseline at Week 76 + 30 days was calculated as vBMD at Week 76 + 30 days minus vBMD at baseline and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Infero-posterior is the lower and back section of the FN. (NCT00679939)
Timeframe: Baseline and Week 76 + 30 days

Adjusted Change From Baseline in Femoral Neck (FN) Supero-anterior Cortical Thickness Via QCT at Week 76 + 30 Days

Cortical thickness was measured by QCT. Change from baseline was calculated as thickness at Week 76 + 30 days minus thickness at Baseline. (NCT00679939)
Timeframe: Baseline and Week 76 + 30 days

Adjusted Change From Baseline in Femoral Neck (FN) Supero-anterior Cortical vBMD Via QCT at Week 76 + 30 Days

vBMD was measured by QCT. Change from Baseline at Week 76 + 30 days was calculated as vBMD at Week 76 + 30 days minus vBMD at baseline and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Supero-anterior is the upper and front section of the FN. (NCT00679939)
Timeframe: Baseline and Week 76 + 30 days

Adjusted Change From Baseline in Femoral Neck (FN) Supero-posterior and Cortical vBMD Via QCT at Week 76 + 30 Days

vBMD was measured by QCT. Change from Baseline at Week 76 + 30 days was calculated as vBMD at Week 76 + 30 days minus vBMD at baseline and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Supero-posterior is the upper and back section of the FN. (NCT00679939)
Timeframe: Baseline and Week 76 + 30 days

Adjusted Change From Baseline in Femoral Neck (FN) Supero-posterior Cortical Thickness Via QCT at Week 76 + 30 Days

Cortical thickness was measured by QCT. Change from baseline was calculated as thickness at Week 76 + 30 days minus thickness at Baseline. (NCT00679939)
Timeframe: Baseline and Week 76 + 30 days

Adjusted Change in Albumin-adjusted Serum Calcium (AASC) From Week 52 to Week 76

AASC levels were measured from blood samples. AASC is the amount of free calcium circulating in the blood and calcium is required for good bone health. Change from Week 52 was calculated as the Week 76 value minus the Week 52 value and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Week 52 and Week 76

Adjusted Change in Femoral Neck (FN) Infero-anterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days

Cortical thickness was measured by QCT. Change was calculated as thickness at Week 76 + 30 days minus thickness at Week 52 + 30 days. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Change in Femoral Neck (FN) Infero-anterior Cortical vBMD Via QCT From Week 52 + 30 Days to Week 76 + 30 Days

vBMD was measured by QCT. Change from Week 52 + 30 days to Week 76 + 30 days was calculated as vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Infero-anterior is the lower and front section of the FN. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Change in Femoral Neck (FN) Infero-posterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days

Cortical thickness was measured by QCT. Change was calculated as thickness at Week 76 + 30 days minus thickness at Week 52 + 30 days. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Change in Femoral Neck (FN) Infero-posterior Cortical vBMD Via QCT From Week 52 + 30 Days to Week 76 + 30 Days

vBMD was measured by QCT. Change from Week 52 + 30 days to Week 76 + 30 days was calculated as vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Infero-posterior is the lower and back section of the FN. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Change in Femoral Neck (FN) Supero-anterior Cortical Thickness Via QCT From Week 52+30 Days to Week 76 + 30 Days

Cortical thickness was measured by QCT. Change was calculated as thickness at Week 76 + 30 days minus thickness at Week 52 + 30 days. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Change in Femoral Neck (FN) Supero-anterior Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days

vBMD was measured by QCT. Change from Week 52 + 30 days to Week 76 + 30 days was calculated as vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Supero-anterior is the upper and front section of the FN. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Change in Femoral Neck (FN) Supero-posterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days

Cortical thickness was measured by QCT. Change was calculated as thickness at Week 76 + 30 days minus thickness at Week 52 + 30 days. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Change in Femoral Neck (FN) Supero-posterior Cortical vBMD Via QCT From Week 52 + 30 Days to Week 76 + 30 Days

vBMD was measured by QCT. Change from Week 52 + 30 days to Week 76 + 30 days was calculated as vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therpay, and region. Supero-posterior is the upper and back section of the FN. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Percent Change From Baseline in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) at Week 52

FN BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Bone mineral density is calculated as the mineral content of a bone divided by the area of the bone. DXA is the principal technique used for measuring BMD. Percent change from Baseline at Week 52 was calculated as (BMD at Week 52 minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Change in FN BMD at Week 52 was only analyzed within the Rosiglitazone arm. (NCT00679939)
Timeframe: Baseline and Week 52

Adjusted Percent Change From Baseline in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) at Week 76+10 Days

FN BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Bone mineral density is calculated as the mineral content of a bone divided by the area of the bone. DXA is the principal technique used for measuring BMD. Percent change from Baseline at Week 76+10 days was calculated as (BMD at Week 76+10 days minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Baseline and Week 76+10 days

Adjusted Percent Change in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) From Week 52 +10 Days to Week 76+10 Days

FN BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Bone mineral density is calculated as the mineral content of a bone divided by the area of the bone. DXA is the principal technique used for measuring BMD. Percent change from Week 52+10 days to Week 76+10 days was calculated as (BMD at Week 76+10 days minus BMD at Week 52+10 days)/BMD at Week 52+10 days x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Week 52+10 days and Week 76+10 days

Adjusted Percent Change in Femoral Neck (FN) Infero-anterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days

Cortical thickness (measured in millimeters) was measured by QCT. Percent change was calculated as (thickness at Week 76 + 30 days minus thickness at Week 52 + 30 days)/thickness at Week 52 + 30 days x 100%. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Percent Change in Femoral Neck (FN) Infero-posterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days

Adjusted Percent Change in Femoral Neck (FN) Supero-anterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days

Adjusted Percent Change in Femoral Neck (FN) Supero-posterior Cortical Thickness Via QCT From Week 52+30 Days to Week 76 + 30 Days

Adjusted Percent Change in Vertebral Trabecular vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days

BMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/vBMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Change From Baseline in Albumin-adjusted Serum Calcium (AASC) at Week 52 and Week 76

AASC levels were measured from blood samples. AASC is the amount of free calcium circulating in the blood and calcium is required for good bone health. Change from baseline was calculated as the Week 52or Week 76 value minus the baseline value and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Baseline, Week 52, and Week 76

Adjusted Percent Change From Baseline in 25-Hydroxyvitamin D (Vitamin D) at Week 52 and Week 76

Vitamin D levels were measured in nanomoles per Liter (nmol/L) from blood samples. Vitamin D is required for good bone health. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Baseline, Week 52, and Week 76

Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76

BSAP and P1NP levels were measured in micrograms per liter (mcg/L) from blood samples. BSAP and P1NP are indicators of bone buildup or formation. GM, geometric mean; SE, standard error. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Baseline, Week 52, and Week 76

Adjusted Percent Change From Baseline in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) at Week 52 and Week 76

CTX levels were measured in picograms per milliliter (pg/ml) from blood samples. CTX is an indicator of bone break down or resorption. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Baseline, Week 52, and Week 76

Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-anterior Cortical Thickness Via QCT at Week 52 + 30 Days and Week 76 + 30 Days

Cortical thickness (measured in millimeters) was measured by QCT. Percent change was calculated as (thickness at Week 52 + 30 days (orWeek 76 + 30 days) minus thickness at Baseline)/thickness at Baseline x 100%. (NCT00679939)
Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-anterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days

vBMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. Percent change from Baseline at Week 52 + 30 days or Week 76 + 30 days was calculated as (vBMD at Week 52 + 30 days (orWeek 76 + 30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Infero-anterior is the lower and front section of the FN. (NCT00679939)
Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-posterior Cortical Thickness Via QCT at Week 52 + 30 Days and Week 76 + 30 Days

Cortical thickness (measured in millimeters) was measured by QCT. Percent change was calculated as (thickness at Week 52 + 30 days (or Week 76 + 30 days) minus thickness at Baseline)/thickness at Baseline x 100%. (NCT00679939)
Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-posterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days

vBMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. Percent change from Baseline at Week 52 + 30 days or Week 76 + 30 days was calculated as (vBMD at Week 52 + 30 days (or Week 76 + 30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Infero-posterior is the lower and back section of the FN. (NCT00679939)
Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Adjusted Percent Change From Baseline in Femoral Neck (FN) Integral, FN Trabecular, and FN Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days

vBMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. Percent change from Baseline at Week 52 + 30 days or Week 76 + 30 days was calculated as (vBMD at Week 52 + 30 days (orWeek 76 + 30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-anterior Cortical Thickness Via QCT at Week 52 + 30 Days and Week 76 + 30 Days

Cortical thickness (measured in millimeters) was measured by QCT. Percent change was calculated as (thickness at Week 52 + 30 days(or Week 76 + 30 days) minus thickness at Baseline)/thickness at Baseline x 100%. (NCT00679939)
Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-anterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days

vBMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. Percent change from Baseline at Week 52 + 30 daysor Week 76 + 30 days was calculated as (vBMD at Week 52 + 30 days(or Week 76 + 30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Supero-anterior is the upper and front section of the FN. (NCT00679939)
Timeframe: Baseline, Week 52 plus 30 days, and Week 76 + 30 days

Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-posterior Cortical Thickness Via QCT at Week 52 + 30 Days and Week 76 + 30 Days

Cortical thickness (measured in millimeters) was measured by QCT. Percent change was calculated as (thickness at Week 52 + 30 days (or Week 76 + 30 days) minus thickness at Baseline)/thickness at Baseline x 100% (NCT00679939)
Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-posterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days

vBMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. Percent change from Baseline at Week 52 + 30 days orWeek 76 + 30 days was calculated as (vBMD at Week 52 + 30 days (or Week 76 + 30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therpay, and region. Supero-posterior is the upper and back section of the FN. (NCT00679939)
Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Intertrochanter Areal BMD Via Quantitative Computed Tomography (QCT) at Week 52 + 30 Days and Week 76 + 30 Days

BMD (measured in grams per centimeters squared [g/cm^2]) was measured by QCT. BMD by QCT is the 2-dimensional volume that mimics the DXA measurement for the same region. Percent change from Baseline at Week 52 + 30 days orWeek 76 + 30 days was calculated as (BMD at Week 52 + 30 days (orWeek 76 + 30 days) minus BMD at baseline)/BMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52

BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Percent change from Baseline at Week 52 was calculated as (BMD at Week 52 minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Baseline and Week 52

Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 10 Days and Week 76 + 10 Days

BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Percent change from Baseline at Week 52 + 10 days or Week 76 + 10 days was calculated as (BMD at Week 52 + 10 days (or Week 76 + 10 days ) minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Baseline, Week 52 + 10 days, and Week 76 + 10 days

Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 30 Days and Week 76 + 30 Days

BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Percent change from Baseline at Week 52 + 30 days or Week 76 + 30 days was calculated as (BMD at Week 52 + 30 days (or Week 76 + 30 days) minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Adjusted Percent Change From Baseline in Intact Parathyroid Hormone (PTH) at Week 52 and Week 76

Intact PTH levels were measured in nanograms per Liter (ng/L) from blood samples. Intact PTH is the amount of PTH circulating in the blood and influences bone health. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Baseline, Week 52, and Week 76

Adjusted Percent Change From Baseline in Intertrochanter Integral, Intertrochanter Trabecular, and Intertrochanter Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days

vBMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. Percent change from Baseline at Week 52 + 30 days or Week 76 + 30 days was calculated as (vBMD at Week 52 + 30 days (or Week 76 + 30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Adjusted Percent Change From Baseline in Total Hip (TH) Integral, TH Trabecular, and TH Cortical vBMD Via QCT at Week 52 + 30 Days and at Week 76 + 30 Days

Volumetric (v)BMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. vBMD is the 3-dimensional density of a region of bone. Cortical bone is dense bone. Trabecular bone is spongy bone. Integral bone is the sum of cortical and trabecular bone measurements. Cortical thickness is the width of the cortical shell. Percent change from Baseline was calculated as (vBMD at Week 52+30 days (or Week 76+30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by ANCOVA with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Adjusted Percent Change From Baseline in Trochanter Integral, Trochanter Trabecular, and Trochanter Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days

vBMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. Percent change from Baseline at Week 52 + 30 days or Week 76 + 30 days was calculated as (vBMD at Week 52 + 30 days (or Week 76 + 30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Adjusted Percent Change From Baseline in Vertebral Trabecular vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days

BMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. Percent change from Baseline at Week 52 + 30 days or Week 76 + 30 days was calculated as (vBMD at Week 52 + 30 days (orWeek 76 + 30 days) minus vBMD at baseline)/vBMD at Baseline x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Baseline, Week 52 + 30 days, and Week 76 + 30 days

Adjusted Percent Change in 25-Hydroxyvitamin D (Vitamin D) From Week 52 to Week 76

Adjusted Percent Change in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) From Week 52 to Week 76

Adjusted Percent Change in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) From Week 52 to Week 76

Adjusted Percent Change in Femoral Neck (FN) Infero-anterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days

vBMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/vBMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Infero-anterior is the lower and front section of the FN. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Percent Change in Femoral Neck (FN) Infero-posterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days

vBMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/vBMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Infero-posterior is the lower and back section of the FN. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Percent Change in Femoral Neck (FN) Integral, FN Trabecular, and FN Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days

vBMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/vBMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Percent Change in Femoral Neck (FN) Supero-anterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days

vBMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/vBMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Supero-anterior is the upper and front section of the FN. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Percent Change in Femoral Neck (FN) Supero-posterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days

vBMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/vBMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therpay, and region. Supero-posterior is the upper and back section of the FN. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Intertrochanter Areal BMD Via Quantitative Computed Tomography (QCT) From Week 52+30 Days to Week 76 + 30 Days

BMD (measured in grams per centimeters squared [g/cm^2]) was measured by QCT. BMD by QCT is the 2-dimensional volume that mimics the DXA measurement for the same region. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (BMD at Week 76 + 30 days minus BMD at Week 52 + 30 days)/BMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+10 Days to Week 76 + 10 Days

BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Percent change from Week 52 + 10 days toat Week 76 + 10 days was calculated as (BMD at Week 76 + 10 days minus BMD at Week 52 + 10 days)/BMD at Week 52 + 10 days x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Week 52 + 10 days and Week 76 + 10 days

Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+30 Days to Week 76 + 30 Days

BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (BMD at Week 76 + 30 days minus BMD at Week 52 + 30 days)/BMD at Week 52 + 30 days x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Percent Change in Intact Parathyroid Hormone (PTH) From Week 52 to Week 76

Adjusted Percent Change in Intertrochanter Integral, Intertrochanter Trabecular, and Intertrochanter Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days

vBMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/vBMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Percent Change in Total Hip (TH) Integral, TH Trabecular, and TH Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days

Volumetric (v)BMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. vBMD is the 3-dimensional density of a region of bone. Cortical bone is dense bone. Trabecular bone is spongy bone. Integral bone is the sum of cortical and trabecular bone measurements. Cortical thickness is the width of the cortical shell. Percent change from Week 52 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/ vBMD at Week 52 + 30 days x 100% and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Adjusted Percent Change in Trochanter Integral, Trochanter Trabecular, and Trochanter Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days

vBMD (measured in milligrams per centimeters cubed [mg/cm^3]) was measured by QCT. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (vBMD at Week 76 + 30 days minus vBMD at Week 52 + 30 days)/vBMD at Week 52 + 30 days x 100% and was assessed by an analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. (NCT00679939)
Timeframe: Week 52 + 30 days and Week 76 + 30 days

Percent Change From Baseline in Free Testosterone at Week 52 and Week 76

Free testosterone levels were measured as a percentage of total testosterone from blood samples. Free testosterone is the amount of testosterone available to the body for use. Percent change from baseline was based on log-transformed data. (NCT00679939)
Timeframe: Baseline, Week 52, and Week 76

Percent Change From Baseline in Serum Estradiol at Week 52 and Week 76

Serum estradiol levels were measured in picomoles per Liter (pmol/L) from blood samples. Estradiol is one form of the female sex hormone estrogen and influences bone health. Percent change from baseline was based on log-transformed data. (NCT00679939)
Timeframe: Baseline, Week 52, and Week 76

Percent Change From Baseline in Sex Hormone Binding Globulin (SHBG) at Week 52 and Week 76

SHBG levels were measured in nanomoles per liter (nmol/L) from blood samples. SHBG binds to estradiol and testosterone and influences the amount of estradiol or testosterone available to the body for use. Percent change from baseline was based on log-transformed data. (NCT00679939)
Timeframe: Baseline, Week 52, and Week 76

Percent Change From Baseline in Total Testosterone at Week 52 and Week 76

Total testosterone levels were measured in nanomoles per Liter (nmol/L) from blood samples. Testosterone is a male sex hormone and influences bone health; total testosterone is the entire amount circulating in blood. Percent change from baseline was based on log-transformed data. (NCT00679939)
Timeframe: Baseline, Week 52, and Week 76

Percent Change in Free Estradiol From Week 52 to Week 76

Free estradiol levels were measured in picomoles per Liter (pmol/L) from blood samples. Free estrodial is the amount of estrogen available to the body for use. Change was based on log-transformed data. (NCT00679939)
Timeframe: Week 52 and Week 76

Percent Change in Free Testosterone From Week 52 to Week 76

Percent Change in Percentage of Free Estradiol From Week 52 to Week 76

Free estradiol levels were measured as a percentage of serum estrogen from blood samples. Free estradiol is the amount of estrogen available to the body for use. Percent change was based on log-transformed data. (NCT00679939)
Timeframe: Week 52 and Week 76

Percent Change in Serum Estradiol From Week 52 to Week 76

Percent Change in Sex Hormone Binding Globulin (SHBG) From Week 52 to Week 76

Percent Change in Total Testosterone From Week 52 to Week 76

Differences in Augmentation Index at Baseline and 3, 6 and 12 Months After Treatment With Metformin or Agonist GLP-1R.

Differences in augmentation index (AI, %) using oscillometry at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R. (NCT03010683)
Timeframe: Baseline, 3 months, 6 months, and 12 months.

Differences in Endothelial Glycocalyx Thickness at Baseline and 3, 6 and 12 Months After Treatment With Metformin or Agonist GLP-1R.

Differences in endothelial glycocalyx thickness as assessed by perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R. High PBR values represent reduced glycocalyx thickness. (NCT03010683)
Timeframe: Baseline, 3 months, 6 months, and 12 months.

Differences in Pulse Wave Velocity at Baseline and 3, 6 and 12 Months After Treatment With Metformin or Agonist GLP-1R.

Differences in carotid-femoral pulse wave velocity (PWV, m/sec) using tonometry at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R. (NCT03010683)
Timeframe: Baseline, 3 months, 6 months and 12 months

Endothelial Glycocalyx and Pulse Wave Velocity.

Association of endothelial glycocalyx thickness as assessed by perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels with pulse wave velocity (PWV, m/sec) at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R. (NCT03010683)
Timeframe: Baseline, 3 months, 6 months, and 12 months.

Percentage of Participants Achieving A1C < 7% at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy

Percentage of participants achieving A1C < 7%, the American Diabetes Association's defined goal for glycemia, at each dose of saxagliptin plus metformin versus metformin alone at Week 24. (NCT00327015)
Timeframe: Week 24

Percentage of Participants Achieving A1C < 7% at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy

Percentage of participants achieving A1C < 7%, the American Diabetes Association's defined goal for glycemia, at each dose of saxagliptin plus metformin versus saxagliptin alone at Week 24. (NCT00327015)
Timeframe: Week 24

Percentage of Participants Achieving A1C ≤6.5% at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy

Percentage of participants achieving A1C ≤6.5%, at each dose of saxagliptin plus metformin versus metformin alone at Week 24. (NCT00327015)
Timeframe: Week 24

Percentage of Participants Achieving A1C ≤6.5% at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy

Percentage of participants achieving A1C ≤6.5%, at each dose of saxagliptin plus metformin versus saxagliptin alone at Week 24. (NCT00327015)
Timeframe: Week 24

Percentage of Participants Requiring Rescue or Discontinuation at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy

Percentage of participants requiring rescue for failing to achieve pre-specified glycemic targets or discontinuing for lack of efficacy within the 24-week treatment period at each dose of saxagliptin plus metformin versus metformin alone. (NCT00327015)
Timeframe: Week 24

Percentage of Participants Requiring Rescue or Discontinuation at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy

Change From Baseline in A1C at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy

Mean change from baseline in A1C at Week 24, adjusted for baseline value. (NCT00327015)
Timeframe: Baseline, Week 24

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy

Mean change from baseline in FPG at Week 24, adjusted for baseline value. (NCT00327015)
Timeframe: Baseline, Week 24

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy

Mean change from baseline in FPG at Week 24, adjusted for baseline value. (NCT00327015)
Timeframe: Baseline, Week 24

Change From Baseline in Hemoglobin A1c (A1C) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy

Mean change from baseline in A1C at Week 24, adjusted for baseline value. (NCT00327015)
Timeframe: Baseline, Week 24

Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, Saxagliptin Plus Metformin Versus Metformin Monotherapy

Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjsuted for baseline value. (NCT00327015)
Timeframe: Baseline, Week 24

Changes From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Oral Glucose Tolerance Test (OGTT) at Week 24, Saxagliptin Plus Metformin Versus Saxagliptin Monotherapy

Mean change from baseline for 0 to 180 minutes PPG AUC at Week 24, adjusted for baseline value. (NCT00327015)
Timeframe: Baseline, Week 24

Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 104

Change from baseline at Week 104 is defined as Week 104 minus Week 0. (NCT00103857)
Timeframe: Week 104

Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 24

Change from baseline at Week 24 is defined as Week 24 minus Week 0. (NCT00103857)
Timeframe: Week 24

Change From Baseline in 2-Hour PMG (Post-Meal Glucose) at Week 54

Change from baseline at Week 54 is defined as Week 54 minus Week 0. (NCT00103857)
Timeframe: Week 54

Change From Baseline in FPG (Fasting Plasma Glucose) at Week 104

Change from baseline at Week 104 is defined as Week 104 minus Week 0. (NCT00103857)
Timeframe: Week 104

Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24

Change from baseline at Week 24 is defined as Week 24 minus Week 0. (NCT00103857)
Timeframe: Week 24

Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54

Change from baseline at Week 54 is defined as Week 54 minus Week 0. (NCT00103857)
Timeframe: Week 54

Change From Baseline in HbA1c (Hemoglobin A1C) at Week 104

HbA1c is measured as a percent. This change from baseline reflects the Week 104 HbA1c percent minus the Week 0 HbA1c percent. (NCT00103857)
Timeframe: Week 104

Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24

HbA1c is measured as a percent. This change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent. (NCT00103857)
Timeframe: Week 24

Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54

HbA1c is measured as a percent. This change from baseline reflects the Week 54 HbA1c percent minus the Week 0 HbA1c percent. (NCT00103857)
Timeframe: Week 54

ACPRg

First phase response from the hyperglycemic clamp (NCT01779362)
Timeframe: 3-months after a medication washout

Insulin Sensitivity, M/I

Clamp measure of insulin sensitivity (NCT01779362)
Timeframe: 3-months after a medication washout

ß-cell Function Measured by Hyperglycemic Clamp Techniques at M12

Participants had 12-months of active therapy. Secondary results at the end of active intervention. (NCT01779362)
Timeframe: Secondary analysis was on all participants with a Month 12 visit.

ß-cell Response Measured by Hyperglycemic Clamp

Clamp measures of ß-cell response, co-primary outcomes (NCT01779362)
Timeframe: 3-months after medication washout (Month 15)

Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c)

Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group (previous oral antihyperglycemic medication [OAM] versus no previous OAM) as fixed effects and baseline HbA1c as a covariate. (NCT01126580)
Timeframe: Baseline, 26 weeks

Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c)

Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Change Version

The Diabetes Treatment Satisfaction Questionnaire change (DTSQc) score is used to assess relative change in participant satisfaction from baseline. The questionnaire consists of 8 items, 6 of which (1 and 4 through 8) assess treatment satisfaction. Each item is rated on a 7-point Likert scale. The scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from -18 (much less satisfied) to +18 (much more satisfied). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score. (NCT01126580)
Timeframe: 52 weeks

Measurement of LY2189265 Drug Concentration for Pharmacokinetics: Area Under the Concentration Curve (AUC)

Evaluable pharmacokinetic concentrations from the 4-week, 13-week, 26-week, and 52-week timepoints were combined and utilized in a population approach to determine the population mean estimate and standard deviation at steady-state. (NCT01126580)
Timeframe: 4 weeks, 13 weeks, 26 weeks, and 52 weeks

Number of Participants With Adjudicated Pancreatitis at 52 Weeks Plus 30-day Follow up

The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 52 weeks plus 30-day follow up. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. (NCT01126580)
Timeframe: Baseline through 52 weeks plus 30-day follow up

Number of Participants With Treatment Emergent Anti-LY2189265 Antibodies

A participant was considered to have treatment emergent LY2189265 anti-drug antibodies (ADA) if the participant had at least one titer that was treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement. The total number of treatment emergent ADA was not analyzed at 26 weeks. (NCT01126580)
Timeframe: Baseline through 52 weeks

Change From Baseline to 26 and 52 Weeks in Blood Pressure

Sitting systolic blood pressure (SBP) and sitting diastolic blood pressure (DBP) were measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline interval as a covariate, and participant as a random effect. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Change From Baseline to 26 and 52 Weeks in Body Mass Index (BMI)

Body mass index is an estimate of body fat based on body weight divided by height squared. Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group as fixed effects and baseline BMI as a covariate. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Change From Baseline to 26 and 52 Weeks in Body Weight

Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group as fixed effects and baseline body weight as a covariate. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Change From Baseline to 26 and 52 Weeks in Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles

The SMBG data were collected at the following 8 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening; 2 hours post-evening meal; bedtime; and 3AM or 5 hours after bedtime. Least Squares (LS) means of the mean of the 8 time points (daily mean) were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group as fixed effects and baseline daily mean as a covariate. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval

The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline interval as a covariate, and participant as a random effect. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate

Electrocardiogram (ECG) heart rate was measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects and baseline interval as a covariate. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Change From Baseline to 26 and 52 Weeks in Fasting Blood Glucose

Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline fasting blood glucose as a covariate, and participant as a random effect. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function

The homeostatic model assessment (HOMA) quantifies insulin resistance and beta-cell function. HOMA2-B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady-state beta cell function (%B) as a percentage of a normal reference population (normal young adults). HOMA2-S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S) as percentages of a normal reference population (normal young adults). The normal reference populations were set at 100%. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline HOMA2 as a covariate, and participant as a random effect. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes

Amylase (total and pancreas-derived [PD]) and lipase concentrations were measured. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Change From Baseline to 26 and 52 Weeks in Pulse Rate

Sitting pulse rate was measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline interval as a covariate, and participant as a random effect. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Change From Baseline to 26 and 52 Weeks in Serum Calcitonin

Change From Baseline to 26 and 52 Weeks in the Diabetes Symptoms Checklist Participant-reported Outcome (DSC-r) Score

"The Diabetes Symptoms Checklist-revised (DSC-r) was designed to assess the presence and perceived burden of diabetes-related symptoms. Respondents were to consider troublesomeness of 34 symptoms on a 5-point scale ranging from 5=extremely to 1=not at all. For symptoms/side-effects not experienced, the item was scored as 0. Symptoms were grouped into the following subscales: psychology-fatigue, psychology-cognitive, neurology-pain, neurology-sensory, cardiology, ophthalmology, hypoglycemia, and hyperglycemia. Subscale scores were calculated as the sum of the given subscale divided by the total number of items in the scale. Total score was computed from the sum of the 8 subscales and ranged from 0 to 40. Higher scores indicate greater symptom burden. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score." (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Change From Baseline to 26 and 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Status Version

The Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) is used to assess participant treatment satisfaction at each study visit. The questionnaire consists of 8 items, 6 of which (1 and 4 through 8) assess treatment satisfaction. Each item is rated on a 7-point Likert scale. Scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from 0 (very dissatisfied) to 36 (very satisfied). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) Score

"The Impact of Weight on Activities of Daily Living (renamed the Ability to Perform Physical Activities of Daily Living [APPADL]) questionnaire contains 7 items that assess how difficult it is for participants to engage in certain activities considered to be integral to normal daily life, such as walking, standing and climbing stairs. Items are scored on a 5-point numeric rating scale where 5 = not at all difficult and 1 = unable to do. The individual scores from all 7 items are summed and a single total score is calculated and may range between 7 and 35. A higher score indicates better ability to perform activities of daily living. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score." (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) Score

The Impact of Weight on Self-Perception (IW-SP) questionnaire contains 3 items that assess how often the participants' body weight affects how happy they are with their appearance and how often they feel self-conscious when out in public. Items are scored on a 5-point numeric rating scale where 5 = never and 1 = always. A single total score is calculated by summing the scores for all 3 items. Total score ranges between 3 and 15, where a higher score is indicative of better self-perception. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up

Information on cardiovascular (CV) risk factors was collected at baseline. Data on any new CV event was prospectively collected using a CV event electronic case report form. Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by an external committee of physicians with cardiology expertise. Nonfatal cardiovascular AEs to be adjudicated included myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions, and cerebrovascular events, including cerebrovascular accident (stroke) and transient ischemic attack. The number of participants with CV events confirmed by adjudication is summarized cumulatively at 52 weeks plus 30-day follow up. Serious and all other non-serious adverse events regardless of causality are summarized in the Reported Adverse Events module. (NCT01126580)
Timeframe: Baseline through 52 weeks plus 30-day follow up

Number of Participants With Treatment Emergent Adverse Events at 26 and 52 Weeks

A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with one or more TEAE is summarized cumulatively at 26 and 52 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. (NCT01126580)
Timeframe: 26 weeks and 52 weeks

Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks

Hypoglycemic events were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of less than or equal to 70 milligrams per deciliter [mg/dL]), or asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 70 mg/dL). A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. (NCT01126580)
Timeframe: Baseline through 26 weeks and 52 weeks

Percent Change From Baseline to 26 and 52 Weeks in Total Cholesterol

Percent changes in total cholesterol were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Percentage Change From Baseline to 26 and 52 Weeks in High Density Lipoprotein Cholesterol (HDL-C)

Percentage changes in HDL-C were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Percentage Change From Baseline to 26 and 52 Weeks in Low Density Lipoprotein Cholesterol (LDL-C)

Percentage changes in LDL-C were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Percentage Change From Baseline to 26 and 52 Weeks in Triglycerides

Percentage changes in triglycerides were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model. (NCT01126580)
Timeframe: Baseline, 26 weeks, and 52 weeks

Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks

The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% was analyzed with a logistic regression model with baseline, prior medication group, and treatment as factors included in the model. (NCT01126580)
Timeframe: 26 weeks and 52 weeks

Rate of Self-reported Hypoglycemic Events at 52 Weeks

Hypoglycemic events were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of less than or equal to 70 milligrams per deciliter [mg/dL]), or asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 70 mg/dL). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 52 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. (NCT01126580)
Timeframe: Baseline through 52 weeks

Time From Rand. to First Occurrence of an Expanded Composite Cardiovascular Outcome Defined as Either Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke, Revascularisation, Hospitalisation for Unstable Angina or for Heart Failure.

Time from randomisation to first occurrence of an expanded composite cardiovascular outcome defined as either cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularisation, hospitalisation for unstable angina or for heart failure. The percentage of subjects experiencing first occurrence of an expanded composite cardiovascular outcome defined as either cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularisation, hospitalisation for unstable angina or for heart failure is presented. (NCT01179048)
Timeframe: from randomisation (visit 3; month 0) to last contact (visit 16; up to month 60+30 days)

Time From Randomisation to All Cause Death

Time from randomisation to all cause death. The percentage of subjects with a death by any cause (all-cause death) is presented. (NCT01179048)
Timeframe: from randomisation (visit 3; month 0) to last contact (visit 16; up to month 60+30 days)

Time From Randomisation to First Occurrence of a Composite Microvascular Outcome

"Time from randomisation to first occurrence of a composite microvascular outcome, defined as any one of the following:~new onset of persistent macroalbuminuria~persistent doubling of serum creatinine~need for continuous renal replacement therapy~death due to renal disease~need for retinal photocoagulation or treatment with intravitreal agents~vitreous haemorrhage~diabetes-related blindness~The percentage of subjects experiencing a first occurrence of a composite microvascular outcome is presented." (NCT01179048)
Timeframe: from randomisation (visit 3; month 0) to last contact (visit 16; up to month 60+30 days)

Time From Randomisation to First Occurrence of Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke (a Composite Cardiovascular Outcome)

Time from randomisation to first occurrence of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke (a composite cardiovascular outcome). The percentage of subjects experiencing a first event of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke (a composite cardiovascular outcome) is presented. (NCT01179048)
Timeframe: from randomisation (visit 3; month 0) to last contact (visit 16; up to month 60+30 days)

Time From Randomisation to Each Individual Component of the Composite Microvascular Outcome and to the Retinopathy and Nephropathy Composite Outcomes Separately.

Time from randomisation to each individual component of the composite microvascular outcome and to the retinopathy and nephropathy composite outcomes separately. The percentage of subjects experiencing each individual component of the composite microvascular outcome are presented. (NCT01179048)
Timeframe: from randomisation (visit 3; month 0) to last contact (visit 16; up to month 60+30 days)

Time From Randomisation to Each Individual Component of the Expanded Composite Cardiovascular Outcome

Time from randomisation to each individual component of the expanded composite cardiovascular outcome. The percentage of subjects experiencing each of the individual component of the expanded composite cardiovascular outcome (defined as either cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularisation, hospitalisation for unstable angina or heart failure) is presented. (NCT01179048)
Timeframe: from randomisation (visit 3; month 0) to last contact (visit 16; up to month 60+30 days)

Adipose Tissue Insulin Sensitivity

Suppression of free fatty acids by low dose insulin (i.e., percentage of reduction of plasma FFA with low dose insulin infusion compared to the baseline state). This was calculated as: 100*((plasma FFA without insulin - plasma FFA with insulin infusion)/plasma FFA without insulin). All measurements are obtained at the same time point during an euglycemic insulin clamp. (NCT00994682)
Timeframe: 18 months

Hepatic Insulin Sensitivity

Suppression of endogenous glucose production (Supp EGP) by low dose insulin (i.e., percentage of reduction of EGP with low dose insulin infusion compared to the baseline state). This was calculated as: 100*((EGP without insulin - EGP with insulin infusion)/EGP without insulin). All measurements are obtained at the same time point during an euglycemic insulin clamp. (NCT00994682)
Timeframe: 18 months

Liver Fat by Magnetic Resonance and Spectroscopy (MRS).

Liver fat content was calculated as the fat fraction: 100*(area under the curve [AUC] of fat peak / [AUC of fat peak + AUC of water peak]). (NCT00994682)
Timeframe: 18 months

Liver Histology (Using Kleiner et al Criteria, Hepatology 2005)

"Number of patients with reduction of at least 2 points in the nonalcoholic fatty liver disease activity score (NAS) (with reduction in at least 2 different histological categories) without worsening of fibrosis. NAS is the sum of the separate scores for steatosis (0-3), hepatocellular ballooning (0-2) and lobular inflammation (0-3), and ranges from 0-8 .~The scoring system is based on the following grading:~Steatosis: 0 = <5%; 1 = 5-33%; 2 = >33-66%; 3 = >66%. Lobular Inflammation: 0 = No foci 1 = <2 foci/200x; 2 = 2-4 foci/200x, 3 = >4 foci/200x. Hepatocyte Ballooning: 0 = None; 1 = Few balloon cells; 2 = Many cells/prominent ballooning. Fibrosis: 0 = None; 1 = Perisinusoidal or periportal; 2 = Perisinusoidal and portal/periportal; 3 = Bridging fibrosis, 4 = Cirrhosis." (NCT00994682)
Timeframe: At 18 months

Number of Participants With Resolution of NASH

Resolution of NASH was defined as absence of NASH after 18 months of therapy in patients with definite NASH (presence of zone 3 accentuation of macrovesicular steatosis of any grade, hepatocellular ballooning of any degree, and lobular inflammatory infiltrates of any amount) at baseline. (NCT00994682)
Timeframe: Month 18

Osteoporotic Fractures

Number of patients with osteoporotic fractures (NCT00994682)
Timeframe: 18 and 36 months

Skeletal Muscle Insulin Sensitivity

Rate of glucose disappearance (Rd) during high-dose insulin infusion. The rate of plasma glucose disappearance was calculated using Steele's non-steady-state equation. (NCT00994682)
Timeframe: 18 months

Total Body Fat

Total body fat measured by dual-energy x-ray absorptiometry (DXA) (NCT00994682)
Timeframe: Months 18

Body Mass Index (BMI)

Bone Mineral Density

Bone mineral density measured at the levels of spine, femoral neck, hip, and wrist by DXA. (NCT00994682)
Timeframe: 18 and 36 months

Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)

Homeostatic model assessment of insulin resistance (HOMA-IR) is a method for assessing insulin resistance (IR) from basal fasting plasma glucose (FPG) and fasting plasma insulin (FPI). It is calculated as (FPG x FPI)/405. (NCT00994682)
Timeframe: 18 and 36 months

Individual Histological Scores

"Number of patients with improvement of at least 1 grade in each of the histological parameters.~Steatosis: 0 = <5%; 1 = 5-33%; 2 = >33-66%; 3 = >66%. Lobular Inflammation: 0 = No foci 1 = <2 foci/200x; 2 = 2-4 foci/200x, 3 = >4 foci/200x. Hepatocyte Ballooning: 0 = None; 1 = Few balloon cells; 2 = Many cells/prominent ballooning. Fibrosis: 0 = None; 1 = Perisinusoidal or periportal, 1A = Mild, zone 3, perisinusoidal delicate fibrosis; 1B = Moderate, zone 3, perisinusoidal dense fibrosis; 1C = Portal/periportal; 2 = Perisinusoidal and portal/periportal; 3 = Bridging fibrosis, 4 = Cirrhosis" (NCT00994682)
Timeframe: Month 18

Liver Transaminases (AST and ALT).

Mean Individual Histological Scores

Mean change in individual scores compared to baseline. Steatosis: 0 = <5%; 1 = 5-33%; 2 = >33-66%; 3 = >66%. Lobular Inflammation: 0 = No foci 1 = <2 foci/200x; 2 = 2-4 foci/200x, 3 = >4 foci/200x. Hepatocyte Ballooning: 0 = None; 1 = Few balloon cells; 2 = Many cells/prominent ballooning. Fibrosis: 0 = None; 1 = Perisinusoidal or periportal; 2 = Perisinusoidal and portal/periportal; 3 = Bridging fibrosis, 4 = Cirrhosis (NCT00994682)
Timeframe: Baseline and Month 18

Mean Individual Histological Scores

Steatosis: 0 = <5%; 1 = 5-33%; 2 = >33-66%; 3 = >66%. Lobular Inflammation: 0 = No foci 1 = <2 foci/200x; 2 = 2-4 foci/200x, 3 = >4 foci/200x. Hepatocyte Ballooning: 0 = None; 1 = Few balloon cells; 2 = Many cells/prominent ballooning. Fibrosis: 0 = None; 1 = Perisinusoidal or periportal; 2 = Perisinusoidal and portal/periportal; 3 = Bridging fibrosis, 4 = Cirrhosis (NCT00994682)
Timeframe: Month 36

Plasma Biomarkers Relevant to Hepatic Inflammation, Apoptosis and Fibrosis (Adiponectin).

Plasma Biomarkers Relevant to Hepatic Inflammation, Apoptosis and Fibrosis (CK-18).

Prevention of the Onset of T2DM and/or Reversal From IFG/IGT to NGT in Non-diabetics.

Number of patients developing T2DM and number of patients regressing to NGT among patients with prediabetes (IFG/IGT). (NCT00994682)
Timeframe: 18 months

Number of Participants With Fracture

Number of participants with confirmed (through an adjudication process) fractures during the study. Circumstances surrounding the fracture, available X-ray and other diagnostic results and healing status were collected for the adjudication process. (NCT00708175)
Timeframe: Up to 18 months.

Percent Change From Baseline to Month 12 in Bone Mineral Density in the Total Proximal Femur by Dual-Energy-Ray Absorptiometry (DXA)

The change in bone mineral density in the total proximal femur at month 12 relative to baseline. DXA is a means of measuring BMD through x-ray. (NCT00708175)
Timeframe: Baseline and Month 12.

Percent Change From Month 12 to Month 18 in Bone Mineral Density in the Total Proximal Femur by DXA

The change in bone mineral density in the total proximal femur at month 18 relative to month 12. DXA is a means of measuring BMD through x-ray. (NCT00708175)
Timeframe: Month 12 and Month 18.

Change in Fasting Plasma Glucose (FPG)

The change between the fasting plasma glucose value collected at each time frame indicated. (NCT00708175)
Timeframe: Baseline and Month 12; Month 12 and Month 18.

Number of Participants Who Converted to Type 2 Diabetes Mellitus (T2DM)

Participants were considered to have converted to T2DM if there were ≥2 consecutive post-Baseline FPG measurements ≥126 mg/dL. Participants meeting criteria were tabulated and summarized by Study Period (Treatment and Follow-up). Conversion to T2DM during Treatment Period occurred if either both of the consecutive post-Baseline high FPG values, or the first of the 2 consecutive high values occurred on or before the first day off study drug. Conversion to T2DM occurred during the Follow-up Period if both consecutive high values occurred after at least 1 day after the Treatment Period. (NCT00708175)
Timeframe: Up to 18 months.

Change From Baseline in Fasting Plasma Glucose of 2.4 Years

Change From Baseline in Matsuda Index of Insulin Sensitivity (There Are no Minimum/Maximum Values)

Insulin sensitivity The Matsuda index was calculated as 10,000/square root of (pre-meal glucose x pre-meal insulin x mean 120 min post-meal glucose x mean 120 min post-meal insulin), with higher numbers indicating better the insulin sensitivity. (NCT00220961)
Timeframe: Baseline versus 2.4 years

Change From Baseline in Plasma Insulin Concentration During Oral Glucose Tolerance Test

Change in Atherosclerosis

Prevention of Type 2 Diabetes

Percentage of Participants with Type 2 Diabetes at 2.4 years Post-randomization (NCT00220961)
Timeframe: 2.4 years

IMCL

Intramyocellular lipid was measured using immunohistochemistry (using oil Red O staining) in muscle biopsy specimens. Oil red O-stained muscle sections were magnified with an Olympus Provis (Tokyo, Japan) light microscope, and images were digitally captured by using a connected charge-coupled device camera (Sony, Tokyo, Japan). Fiber-typed and oil red O-stained fibers were matched. The oil red O staining intensity of either type 1 or 2 muscle fibers was quantified using National Institutes of Health Image program (http://rsb.info.nih.gov/nih-image/). By adjusting a density threshold, the software was set to recognize the presence of one fat droplet only if its highlighted surface was exceeding 0.40 μm2 or larger. Muscle lipid content was calculated by total area of lipid droplets in a given muscle fiber divided by the total area of the same fiber. The mean number of fibers analyzed per sample was 40 for type 1 and 2 muscle fibers (NCT00470262)
Timeframe: 3 months

Insulin Sensitivity

Insulin sensitivity was measure through frequently sampled intravenous glucose tolerance test. Subjects presented to research center fasting. Blood samples were collected at -21, -11, and -1 minutes. At time t=0 initiates the start of the IVGTT and the injection of glucose into the non-sampling arm. The glucose dose was calculated as 11.4g/m2 of body surface area, given as a 50% dextrose solution. This glucose injection was administered over 60 seconds or less. At time t=20 minutes, an insulin dose of 0.04u/kg was administered over 30 seconds. Blood samples were collected at times t=2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 19, 22, 23, 24, 25, 27, 30, 40, 50, 70, 90, 100, 120, 140, 160, and 180. If blood sugar did not return to a steady state the test was continued to t= 210 or t= 240. (NCT00470262)
Timeframe: 3 months

Body Composition -- BMI

Body mass index (BMI) measured in kg per meters squared. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. (NCT00081328)
Timeframe: 24 months

Body Composition -- Bone Density

Measured by DXA, both whole body scan and AP-spine scan. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. In addition, in about 1/3 of participants DXA scans could not be obtained on participants weighing more than 300 pounds (136 kg), the upper limit in size set by the machine manufacturers. Scans were considered invalid if a body part (e.g., arm, leg) was completely off or partially off the scanner, there was hand-hip overlap, or there was motion or movement during the scan. (NCT00081328)
Timeframe: 24 months

Body Composition -- Fat Mass

Determined by DXA whole body scan. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. In addition, in about 1/3 of participants DXA scans could not be obtained on participants weighing more than 300 pounds (136 kg), the upper limit in size set by the machine manufacturers. Scans were considered invalid if a body part (e.g., arm, leg) was completely off or partially off the scanner, there was hand-hip overlap, or there was motion or movement during the scan. (NCT00081328)
Timeframe: 24 months

Body Composition -- Waist Circumference

Waist circumference (cm) measured at the iliac crest at its outermost point with the measuring tape placed around the participant in a horizontal plane parallel to the floor at the mark and the measurement teken at the end of normal expiration without the tape compressing the skin. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. (NCT00081328)
Timeframe: 24 months

Comorbidity -- Hypertension

A diagnosis was made by an out-of-range value >=95th percentile or systolic >=130 or diastolic >=80 sustained over 6 months or on an anti-hypertensive medication. (NCT00081328)
Timeframe: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.

Comorbidity -- LDL Dyslipidemia

A diagnosis was made from out-of-range value >= 130 mg/dL sustained over 6 months or put on lipid lowering medication. (NCT00081328)
Timeframe: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.

Comorbidity -- Triglycerides Dyslipidemia

A diagnosis was made by an out-of-range value >=150 mg/dL sustained over 6 months or on appropriate lipid lowering medication. (NCT00081328)
Timeframe: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.

Insulin Secretion

Insulinogenic index determined from OGTT as difference in insulin at 30 minutes minus 0 minutes divided by difference in glucose at 30 minutes minus 0 minutes. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. (NCT00081328)
Timeframe: 24 months

Insulin Sensitivity

All participants were followed to 24 months. Insulin sensitivity is measured from OGTT as inverse of fasting insulin (mL/uU). The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. (NCT00081328)
Timeframe: 24 months

Number of Serious Adverse Events

Number of serious adverse events reported during the trial. Participant could have multiple episodes reported. (NCT00081328)
Timeframe: Reported as occurred during study follow-up - 2 years to 6.5 years from randomization.

Treatment Failure (Loss of Glycemic Control)

Defined as A1c persistently >=8% over a 6-month period or persistent metabolic decompensation (inability to wean insulin within 3 months of initiation or the occurrence of a second episode within three months of discontinuing insulin) (NCT00081328)
Timeframe: Study duration - 2 years to 6.5 years of follow up from randomization

Percentage Reduction in C-reactive Protein (CRP)

Incidence of Development of Type 2 Diabetes Mellitus in Participants With IGT and/or IFG

The incidence was determined by calculating the proportion of randomized participants without diabetes at randomization who either developed diabetes during the study or who were classified as having possible diabetes based on results of two oral glucose tolerance tests (OGTT) performed after the last follow-up visit (within 21-28 days for OGTT#1 and within 10-14 weeks for OGTT#2). (NCT00069784)
Timeframe: from randomization until the last follow-up visit or last OGTT (median duration of follow-up: 6.2 years)

Number of Patients With First Occurrence of Any Type of Cancer

Data on cancers that occurred in association with hospitalizations were collected systematically in both groups from the start of the study. All reported cancers occurring during the trial (new or recurrent) were adjudicated by the Event Adjudication Committee. (NCT00069784)
Timeframe: from randomization until study cut-off date (median duration of follow-up: 6.2 years)

Total Mortality (All Causes)

Number of deaths due to any cause (NCT00069784)
Timeframe: from randomization until study cut-off date (median duration of follow-up: 6.2 years)

Composite Diabetic Microvascular Outcome (Kidney or Eye Disease)

"The composite outcome used to analyze microvascular disease progression contained components of clinical events:~the occurrence of laser surgery or vitrectomy for diabetic retinopathy (DR);~the development of blindness due to DR;~the occurrence of renal death or renal replacement therapy; as well as the following laboratory-based events:~doubling of serum creatinine; or~progression of albuminuria (from none to microalbuminuria [at least 30 mg/g creatinine], to macroalbuminuria [at least 300 mg/g creatinine])." (NCT00069784)
Timeframe: from randomization until study cut-off date (median duration of follow-up: 6.2 years)

Composite of the First Occurrence of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI) or Nonfatal Stroke

"Number of participants with a first occurrence of one of the above events.~The outcome's evaluation is based on the number of such positively-adjudicated first events occurring for patients assigned to the study groups. Assessments of the above events were reviewed by the Event Adjudication Committee who was kept blinded to the group assignment of participants.~Statistical analysis is performed on the time from randomization to the first occurrence of the events. Number of participants with a composite endpoint (i.e. with first occurrence of CV death, nonfatal MI or nonfatal stroke) is provided in the first row of the statistical table." (NCT00069784)
Timeframe: from randomization until study cut-off date (median duration of follow-up: 6.2 years)

Composite of the First Occurrence of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, Revascularization Procedure or Hospitalization for Heart Failure (HF)

"Number of participants with a first occurrence of one of the above events (revascularization procedures included coronary artery bypass graft, percutaneous transluminal coronary angioplasty (PTCA) i.e. balloon, PTCA with stent, other percutaneous intervention, carotid angioplasty with/without stent, carotid endarterectomy, peripheral angioplasty with or without stent, peripheral vascular surgery, and limb amputation due to vascular disease).~The outcome's evaluation is based on the number of such positively-adjudicated first events occurring for patients assigned to the study groups. Assessments of the above events were reviewed by the Event Adjudication Committee who was kept blinded to the group assignment of participants.~Statistical analysis is performed on the time from randomization to the first occurrence of the events. Number of participants with a composite endpoint (i.e. with first occurrence of the events) is provided in the first row of the statistical table." (NCT00069784)
Timeframe: from randomization until study cut-off date (median duration of follow-up: 6.2 years)

Number of Patients With Various Types of Symptomatic Hypoglycemia Events

"Symptomatic hypoglycemia was defined as an event with clinical symptoms consistent with hypoglycemia, based on data recorded in the participant's diary. These were further categorized as confirmed (ie, with a concomitant home glucose reading ≤54 mg/dL [≤3.0 mmol/L]) or unconfirmed.~Severe hypoglycemia was defined as an event with clinical symptoms consistent with hypoglycemia in which the participant required the assistance of another person, and one of the following:~the event was associated with a documented self-measured or laboratory plasma glucose level ≤36 mg/dL (≤2.0 mmol/L), or~the event was associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration." (NCT00069784)
Timeframe: on-treatment period (median duration of follow-up: 6.2 years)

Death From Any Cause in the Glycemia Trial.

"Time to death from any cause. Secondary measure for Glycemia Trial.~A finding of higher mortality in the intensive-therapy group led to an early discontinuation of therapy after a mean of 3.5 years of follow-up. Intensive arm participants were transitioned to standard arm strategy over a period of 0.2 year and followed for an additional 1.2 years to the planned end of the Glycemia Trial while participating in one of the other sub-trials (BP or Lipid)." (NCT00000620)
Timeframe: 4.9 years

First Occurrence of a Major Cardiovascular Event (MCE); Specifically Nonfatal Heart Attack, Nonfatal Stroke, or Cardiovascular Death (Measured Throughout the Study) in the Glycemia Trial.

"Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. This was the primary outcome measure in all three trials: Glycemia (all participants), Blood Pressure (subgroup of participants not in Lipid Trial), and Lipid (subgroup of participants not in Blood Pressure Trial).~In the Glycemia Trial, a finding of higher mortality in the intensive arm group led to an early discontinuation of therapy after a mean of 3.5 years of follow-up. Intensive arm participants were transitioned to standard arm strategy over a period of 0.2 year and followed for an additional 1.2 years to the planned end of the Glycemia Trial while participating in one of the other sub-trials (BP or Lipid) to their planned completion." (NCT00000620)
Timeframe: 4.9 years

First Occurrence of Major Cardiovascular Event (MCE) in the Blood Pressure Trial.

Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Primary outcome for Blood Pressure Trial. (NCT00000620)
Timeframe: 4.7 years

First Occurrence of Major Cardiovascular Event (MCE) in the Lipid Trial.

Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death in Lipid Trial participants. (NCT00000620)
Timeframe: 4.7 years

First Occurrence of MCE or Revascularization or Hospitalization for Congestive Heart Failure (CHF) in Lipid Trial.

Time to first occurrence of nonfatal myocardial infarction, nonfatal stroke, cardiovascular death, revascularization procedure or hospitalization for CHF in Lipid Trial participants. (NCT00000620)
Timeframe: 4.7 years

Stroke in the Blood Pressure Trial.

Time to first occurrence of nonfatal or fatal stroke among participants in the BP Trial. (NCT00000620)
Timeframe: 4.7 years

Primary Major Macrovascular Events

Myocardial infarction (MI), intervention for coronary artery or Peripheral Vascular Disease (PVD), severe inoperable Coronary Artery Disease (CAD), new or worsening Congestive Heart Failure (CHF), stroke, Cardiovascular (CV) death, or amputation for ischemic gangrene. (NCT00032487)
Timeframe: Post baseline time to the first major macrovascular event up to 82 months

Secondary Endpoint

New or worsening angina, new transient ischemic attack (TIA), new intermittent claudication or critical limb ischemia with Doppler evidence or total mortality. (NCT00032487)
Timeframe: Post baseline time to first event up to 82 months

Percent Incidence of All-cause Mortality (Intent to Treat Population)

Percent incidence of all-cause mortality is reported as the percentage of participants who died due to any cause. (NCT00790205)
Timeframe: Up to 5 years

Percent Incidence of All-cause Mortality (Per Protocol Population)

Percent incidence of all-cause mortality is reported as the percentage of participants who died due to any cause. (NCT00790205)
Timeframe: Up to 5 years

Percent Incidence of CHF Requiring Hospitalization (Intent to Treat Population)

Percent incidence of CHF requiring hospitalization was reported as the percentage of participants who were admitted to the hospital for CHF. (NCT00790205)
Timeframe: Up to 5 years

Percent Incidence of Congestive Heart Failure (CHF) Requiring Hospitalization (Per Protocol Population)

Percent incidence of CHF requiring hospitalization was reported as the percentage of participants who were admitted to the hospital for CHF. (NCT00790205)
Timeframe: Up to 5 years

Percentage of Participants Who Initiated Chronic Insulin Therapy (Intent to Treat Population)

Chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months. (NCT00790205)
Timeframe: Up to 5 years

Percentage of Participants Who Initiated Chronic Insulin Therapy (Per Protocol Population)

Chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months. (NCT00790205)
Timeframe: Up to 5 years

Percentage of Participants With First Confirmed Cardiovascular (CV) Event of Major Adverse Cardiovascular Event (MACE) Plus (Per Protocol Population)

Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization. (NCT00790205)
Timeframe: Up to 5 years

Percentage of Participants With First Confirmed CV Event of MACE (Intent to Treat Population)

CV composite endpoint of MACE which includes CV-related death, nonfatal MI, or nonfatal stroke. (NCT00790205)
Timeframe: Up to 5 years

Percentage of Participants With First Confirmed CV Event of MACE (Per Protocol Population)

CV composite endpoint of MACE which includes CV-related death, nonfatal MI, or nonfatal stroke. (NCT00790205)
Timeframe: Up to 5 years

Percentage of Participants With First Confirmed CV Event of Major Adverse Cardiovascular Event (MACE) Plus (Intent to Treat Population)

Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization. (NCT00790205)
Timeframe: Up to 5 years

Percentage of Participants With Initiation of Co-interventional Agent (Intent to Treat Population)

In participants not receiving insulin at baseline, time to addition of first co-interventional agent (i.e., next oral AHA or chronic insulin, where chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.) (NCT00790205)
Timeframe: Up to 5 years

Percentage of Participants With Initiation of Co-interventional Agent (Per Protocol Population)

In participants not receiving insulin at baseline, time to addition of first co-interventional agent (i.e., next oral antihyperglycemic agent [AHA] or chronic insulin, where chronic insulin therapy is defined as a continuous period of insulin use of more than 3 months.) (NCT00790205)
Timeframe: Up to 5 years

Change From Baseline in HbA1c Over Time (Intent to Treat Population)

HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Estimated mean difference between sitagliptin and placebo controlling for baseline HbA1c and region. (NCT00790205)
Timeframe: Baseline and up to 4 years

Change From Baseline in HbA1c Over Time (Per Protocol Population)

Change From Baseline in Renal Function Over Time (Intent to Treat Population)

Change in renal function based on eGFR using the MDRD method. (NCT00790205)
Timeframe: Baseline and up to 5 years

Change From Baseline in Renal Function Over Time (Per Protocol Population)

Change in renal function based on estimated glomerular filtration rate [eGFR] using the Modification of Diet in Renal Disease [MDRD] method. (NCT00790205)
Timeframe: Baseline and up to 5 years

Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Intent to Treat Population)

Change from baseline reflects the difference between the urine albumin:creatinine ratio reported time point and baseline value. (NCT00790205)
Timeframe: Baseline and up to 5 years

Change From Baseline in Urine Albumin:Creatinine Ratio Over Time (Per Protocol Population)

Change from baseline reflects the difference between the urine albumin:creatinine ratio reported time point and baseline value. (NCT00790205)
Timeframe: Baseline and up to 5 years

Adjusted Mean Change From Baseline in A1C Levels (Last Observation Carried Forward [LOCF])

Change from baseline: post-pre. Adjusted for baseline (value and metformin use). ANCOVA model: difference between week t and baseline values=baseline values + treatment + metformin use (NCT00757588)
Timeframe: Baseline to Week 24

Change From Baseline in 120-minute PPG Values During an MTT

An MTT is a 2-part test that measures glucose and insulin levels after an overnight fast and before ingesting a meal consisting of a nutritional drink and power bar and again at prespecified times (30, 60, 120, and 180 minutes) after the start of ingestion of the meal. (NCT00757588)
Timeframe: Baseline to Week 24

Change From Baseline in Fasting Plasma Glucose Values

Change From Baseline in Mean Total Daily Dose of Insulin (MTDDI) (LOCF)

Based on information recorded in the participant's daily diary. The MTDDI was calculated at every visit using the values patients recorded since the last regularly scheduled visit (minimum of 80% of days with a value). At every visit, the MTDDI was compared with the participant's baseline MTDDI (measured during a 4-week lead-in period) to identify any changes in insulin use at that visit compared with insulin use at baseline. (NCT00757588)
Timeframe: Baseline to Week 24

Change From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Meal Tolerance Test (MTT)

Number of Participants With Abnormal Changes From Baseline in Electrocardiogram (ECG) Results

"ECG abnormalities included those in nonspecific other categories (Other nonspecific ST/T, Other intraventricular conduction defect, Other, and Other rhythm abnormalities)and nonspecific findings, such as sinus bradycardia, sinus arrythmia, sinus tachycardia, poor R-wave progression, and ventricular premature contractions." (NCT00757588)
Timeframe: Baseline to Week 52

Percentage of Participants Achieving a Therapeutic Glycemic Response

Therapeutic glycemic response is defined as an A1C<7%. Significance was not interpreted with a p value. (NCT00757588)
Timeframe: Baseline to Week 24

Mean Changes From Baseline in Heart Rate

(NCT00757588)
Timeframe: Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52

Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings

(NCT00757588)
Timeframe: Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52

Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs

An AE is any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; requires inpatient hospitalization; or prolongs existing hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment. (NCT00757588)
Timeframe: Baseline to Week 52, continuously

Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period

"Marked abnormality=a laboratory value lying outside the predefined criteria and more extreme (farther from the limit)on-treatment than at baseline. ULN=upper limit of normal; LLN=lower limit of normal; prx=pre-RX=pretreatment.~Criteria 1: if prx=0 use >=2, if prx=0.5 or 1 use >=3, if prx=2 use 4." (NCT00757588)
Timeframe: Baseline and during and up to 14 days after last dose of study drug (in Week 52)

Percentage of Participants With Reported and Confirmed Hypoglycemia

Confirmed hypoglycemia=fingerstick glucose measurement of ≤50 mg/dL with associated symptoms/ (NCT00757588)
Timeframe: Baseline to Week 52

Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF)

Absolute lymphocyte count=value*10^3 c/uL (NCT00757588)
Timeframe: Baseline and Weeks 24 and 52

Shift in Platelet Counts From Baseline to Selected Visits (LOCF)

Platelet count=value*10^9 c/L (NCT00757588)
Timeframe: Baseline and Weeks 24 and 52

Mean Slope of the Regressions of Change From Week 24 to Week 104 in HbA1c

Mean slopes of regression of change from Week 24 to Week 104 in HbA1c for saxagliptin added on to metformin versus glipizide added on to metformin (Full Analysis Set) achieved by fitting a mixed model with subject specific slopes for the time effect (weeks on randomized treatment was utilized). This analysis gives an assessment of the durability of the HbA1c effect. (NCT00575588)
Timeframe: Week 24 to Week 104

Mean Slope of the Regressions of Change From Week 24 to Week 52 in HbA1c

Mean slopes of regression of change from Week 24 to Week 52 in HbA1c for saxagliptin added on to metformin versus glipizide added on to metformin (Per Protocol Analysis Set) achieved by fitting a mixed model with subject specific slopes for the time effect (weeks on randomized treatment was utilized). This analysis gives an assessment of the durability of the HbA1c effect. (NCT00575588)
Timeframe: Week 24 to Week 52

Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 104 Weeks

Proportion of participants reporting at least one episode of any hypoglycaemic event for saxagliptin added on to metformin versus glipizide added on to metformin over 104 weeks (Safety Analysis Set) (NCT00575588)
Timeframe: Baseline, Week 104

Proportion of Participants Reporting at Least One Episode of Any Hypoglycaemic Event Over 52 Weeks

Proportion of participants reporting at least one episode of any hypoglycaemic event for saxagliptin added on to metformin versus glipizide added on to metformin over 52 weeks (Safety Analysis Set) (NCT00575588)
Timeframe: From Baseline to Week 52

Body Weight Change From Baseline to Week 104

Adjusted mean change from baseline in Body Weight achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 104. Body Weight is a continuous measure, the change from baseline for each participant is calculated as the Week 104 value minus the baseline value. (NCT00575588)
Timeframe: Baseline, Week 104

Body Weight Change From Baseline to Week 52

Adjusted mean change from baseline in Body Weight achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 52 (Safety Analysis Set). Body Weight is a continuous measure, the change from baseline for each participant is calculated as the Week 52 (LOCF) value minus the baseline value. (NCT00575588)
Timeframe: Baseline, Week 52 (Last Observation Carried Forward)

Hemoglobin A1c (HbA1c) Change From Baseline to Week 104

Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 104 (Full Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 104 value minus the baseline value. (NCT00575588)
Timeframe: Baseline, Week 104

Hemoglobin A1c (HbA1c) Change From Baseline to Week 52

Adjusted mean change from baseline in HbA1c achieved with saxagliptin added on to metformin versus glipizide added on to metformin at Week 52 (Per Protocol Analysis Set). HbA1c is a continuous measure, the change from baseline for each participant is calculated as the Week 52 value minus the baseline value. (NCT00575588)
Timeframe: Baseline to 52 Weeks

Change in Body Weight From Baseline to Year 3

Change in Body weight from baseline to Year 3. (NCT00359762)
Timeframe: Baseline, Year 3 in Period II

Change in DI30/DG30 Ratio From Baseline to Endpoint

Change in DI30/DG30 ratio from baseline to endpoint. (NCT00359762)
Timeframe: Baseline, end of Period II (up to 4.5 years)

Change in Disposition Index From Baseline to Endpoint

Change in disposition index from baseline to endpoint. (NCT00359762)
Timeframe: Baseline, end of Period II (up to 4.5 years)

Change in Fasting Plasma Glucose From Baseline to Endpoint

Change in fasting plasma glucose from baseline to endpoint. (NCT00359762)
Timeframe: Baseline, end of Period II (up to 4.5 years)

Change in Fasting Proinsulin/Insulin Ratio From Baseline to Endpoint.

Change in fasting proinsulin (measured in pmol/L)/insulin (measured in pmol/L) ratio from baseline to endpoint. (NCT00359762)
Timeframe: Baseline, end of Period II (up to 4.5 years)

Change in HbA1c From Baseline to Endpoint

Change in HbA1c from baseline to endpoint. Endpoint for HbA1c was defined as the HbA1c measured at the treatment failure for patients reaching primary endpoint and was the last observation in study period II for other patients (either followed until the end of the study period II or discontinuing the study). (NCT00359762)
Timeframe: Baseline, end of Period II (up to 4.5 years)

Change in HbA1c From Baseline to Year 2 for Patients Not Randomized at Entry in Period III

Change in HbA1c from baseline to Year 2. (NCT00359762)
Timeframe: Baseline in Period III, Year 2 in Period III

Change in HbA1c From Baseline to Year 2 for Patients Randomized at Entry in Period III

Change in HbA1c from baseline to Year 2. (NCT00359762)
Timeframe: Baseline in Period III, Year 2 in Period III

Change in HbA1c From Baseline to Year 3

Change in HbA1c from baseline to Year 3. (NCT00359762)
Timeframe: Baseline, Year 3 in Period II

Change in HOMA-B From Baseline to Endpoint

Change in HOMA-B from baseline to endpoint. (NCT00359762)
Timeframe: Baseline, end of Period II (up to 4.5 years)

Change in Postprandial (2 Hours) Plasma Glucose From Baseline to Endpoint

Change from baseline in postprandial (2 hours) plasma glucose to endpoint. (NCT00359762)
Timeframe: Baseline, end of Period II (up to 4.5 years)

Diastolic Blood Pressure at Year 3

Diastolic Blood pressure at Year 3. (NCT00359762)
Timeframe: Year 3 in Period II

Disposition Index at Year 3

Disposition Index at Year 3. Disposition index was calculated as (DI30/DG30 ratio)/(HOMA index for insulin resistance (HOMA-IR)); where HOMA-IR=(fasting insulin (measured in pmol/L) x fasting glucose (measured in mmol/L))/(22.5 x 7.175). (NCT00359762)
Timeframe: Year 3 in Period II

Fasting Plasma Glucose at Year 3

Fasting Proinsulin/Insulin Ratio at Year 3

Fasting proinsulin (measured in pmol/L)/insulin (measured in pmol/L) ratio at Year 3. (NCT00359762)
Timeframe: Year 3 in Period II

Heart Rate at Year 3

High-density Lipoprotein (HDL) Cholesterol at Year 3

Homeostasis Model Assessment of Beta-cell Function (HOMA-B) at Year 3

HOMA-B at Year 3. HOMA-B is an index of beta-cell function and was calculated as: HOMA-B = (20 x fasting insulin (measured in pmol/L))/((fasting glucose (measured in mmol/L) - 3.5) x 7.175). (NCT00359762)
Timeframe: Year 3 in Period II

Hypoglycemia Rate Per Year

All hypoglycemia episodes were taken into account. Severe hypoglycemia: event requiring assistance of another person to administer carbohydrate, glucagons, or other resuscitative actions; Documented symptomatic hypoglycemia: event with typical symptoms accompanied by a measured plasma glucose concentration <=70 mg/dL; Asymptomatic hypoglycemia: event not accompanied by typical symptoms but with a measured plasma glucose concentration <=70 mg/dL; Probable symptomatic hypoglycemia: event with symptoms not accompanied by a plasma glucose determination. (NCT00359762)
Timeframe: Baseline to end of Period II (up to 4.5 years)

Hypoglycemia Rate Per Year in Period III

Postprandial (2 Hours) Plasma Glucose at Year 3

Postprandial (2 hours) plasma glucose at Year 3. (NCT00359762)
Timeframe: Year 3 in Period II

Ratio of the 30 Minute Increment in Plasma Insulin Concentration and the 30 Minute Increment in Plasma Glucose During the Oral Glucose Tolerance Test (DI30/DG30 Ratio) at Year 3

DI30/DG30 at Year 3. DI30/DG30 ratio was calculated as (30 minute post prandial insulin - fasting insulin) (measured in pmol/L)/(30 minute post prandial glucose - fasting glucose) (measured in mmol/L). (NCT00359762)
Timeframe: Year 3 in Period II

Systolic Blood Pressure at Year 3

Time to Treatment Failure

Treatment failure is defined as one of the following:1. HbA1c exceeding 9% at any visit after the initial 3 months of treatment (i.e., earliest at Month 6), on the maximally tolerated dose of antidiabetic agents. 2. HbA1c exceeding 7% at 2 consecutive visits 3 months apart, after the initial 6 months of treatment (i.e., earliest at Month 9), on the maximally tolerated dose of antidiabetic agents. (NCT00359762)
Timeframe: Baseline to end of Period II (up to 4.5 years)

Total Cholesterol at Year 3

Triglycerides at Year 3

Number of Patients With Treatment Failure

Coefficient of Variation at 26 Weeks Minus Coefficient of Variation at Baseline

The change in the coefficient of variation (CV) of continuous glucose readings, as assessed by Continuous Glucose Monitoring (CGM) (NCT01524705)
Timeframe: At baseline, 6 months of intervention

HbA1C Levels

% of glycosylated hemoglobin in whole blood at 26 weeks (NCT01524705)
Timeframe: Baseline vs 26 weeks

Number of Participants With Hypoglycemia

Severe hypoglycemia-documented glucose <50mg/dl (participant journal), and hypoglycemic attacks requiring hospitalization, or treatment by emergency personnel. (NCT01524705)
Timeframe: 26 weeks

Weight Change During Trial

Weight in kg at 26 weeks minus weight at baseline. (NCT01524705)
Timeframe: Baseline vs 26 weeks

Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and a Sulfonylurea in Combination With Metformin

This change from baseline reflects the 2-hr PMG level at Week 24 minus the 2-hr PMG level at Week 0. (NCT01590771)
Timeframe: Baseline and Week 24

Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone

This change from baseline reflects the 2-hr PMG level at Week 24 minus the 2-hr PMG level at Week 0. (NCT01590771)
Timeframe: Baseline and Week 24

Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin

This change from baseline reflects the 2-hr PMG level at Week 24 minus the 2-hr PMG level at Week 0. (NCT01590771)
Timeframe: Baseline and Week 24

Change From Baseline in A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone

A1C was measured as a percent. This change from baseline reflects the A1C percent at Week 24 minus the A1C percent at Week 0. (NCT01590771)
Timeframe: Baseline and Week 24

Change From Baseline in A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin

A1C was measured as a percent. This change from baseline reflects the A1C percent at Week 24 minus the A1C percent at Week 0. (NCT01590771)
Timeframe: Baseline and Week 24

Change From Baseline in A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea in Combination With Metformin

A1C was measured as a percent. This change from baseline reflects the A1C percent at Week 24 minus the A1C percent at Week 0. (NCT01590771)
Timeframe: Baseline and Week 24

Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone

This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0. (NCT01590771)
Timeframe: Baseline and Week 24

Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin

This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0. (NCT01590771)
Timeframe: Baseline and Week 24

Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea in Combination With Metformin

This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0. (NCT01590771)
Timeframe: Baseline and Week 24

Number of Participants Who Discontinued Study Drug Due to an Adverse Event

An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of pre-existing conditions. (NCT01590771)
Timeframe: Up to 24 weeks

Number of Participants Who Experienced an Adverse Event

Change in HbA1c From Baseline to Week 24 for Subjects With a Baseline HbA1c of ≥ 7.5% Who Were Taking at Least One Oral Hypoglycemia Agent (OHA) at Baseline.

The difference between Cycloset and placebo in the change in HbA1c from baseline to Week 24 was analyzed for subjects with a baseline HbA1c of ≥ 7.5% who were taking at least one oral hypoglycemia agent (OHA) at baseline. The primary analysis was based on subjects from the evaluable per protocol efficacy (EPPE) analysis set with a secondary analysis using subjects from the intent to treat efficacy (ITTE) analysis set for subjects completing 24 weeks of treatment. Change is reported as the absolute difference in % HbA1c. (NCT00377676)
Timeframe: Baseline to week 24

Change in HbA1c From Baseline to Week 24 in Subjects Failing Treatment With Metformin Plus a Sulfonylurea

"Change in HbA1c from baseline to week 24 in subjects failing treatment with metformin plus a sulfonylurea with failure defined as having a baseline HbA1c value of ≥ 7.5%. Change was measured at week 24 after randomization in subjects having no major protocol violations.~Change is reported as the absolute difference in % HbA1c." (NCT00377676)
Timeframe: Baseline to week 24

Number of Subjects Experiencing Serious Cardiovascular Adverse Events

The secondary safety endpoint is number subjects with occurrences of first cardiovascular SAE (myocardial infarction, stroke, in-patient hospitalization for heart failure, angina or revascularization surgery). (NCT00377676)
Timeframe: Baseline to week 52.

Subjects Experiencing Serious Adverse Events

Number of subjects reporting all-cause Serious Adverse Events (SAEs) for usual drug therapy plus Cycloset vs. that for usual drug therapy (UDT) plus placebo from baseline to week 52. (NCT00377676)
Timeframe: From baseline to week 52.

Echocardiographic Epicardial Fat Thickness

Echocardiographic epicardial fat thickness is an non invasive, inexpensive, reproducible and direct measure of visceral fat. In fact, epicardial fat strongly reflects the intra-abdominal and intra-myocardial fat accumulation as measured by magnetic resonance imaging procedures. (NCT02014740)
Timeframe: 6 months

Change in 2-hour Postprandial Glucose Concentrations From Baseline to Week 16 (Visit 8)

The change in 2-hour postprandial plasma glucose from baseline (Day 1) to Visit 8 (Week 16) was analyzed using a general linear model including treatment, and baseline HbA1c stratum (< 9% or ≥ 9%) as fixed factors, and the baseline 2-hour postprandial plasma glucose concentrations as a covariate. (NCT01652729)
Timeframe: Baseline to Week 16

Change in Body Weight (kg) From Baseline to Week 28

The change in body weight (kg) from baseline (Day 1) to Week 28/Study Termination. (NCT01652729)
Timeframe: Baseline to Week 28

Change in Fasting Plasma Glucose Concentrations From Baseline to Week 28

The change in fasting plasma glucose concentrations from baseline (Day 1) to Week 28/Study Termination. (NCT01652729)
Timeframe: Baseline to Week 28

Change in HbA1c (Glycosylated Hemoglobin) From Baseline to Week 28

Absolute change in HbA1c from baseline (Day 1, Visit 3) to Week 28/Study Termination (Visit 11). Hypothesis testing on the primary endpoint followed a serial gated procedure with all tests carried out at a 2-sided significance level of 0.05 to protect the family-wise error rate. These tests were conducted sequentially, and are presented in the statistical analysis section below in the order in which they were performed; each test was the gatekeeper of later tests. (NCT01652729)
Timeframe: Baseline to Week 28

Percentage of Subjects Achieving HbA1c <7% at Week 28

Percentage of subjects achieving HbA1c target values of < 7.0% at Week 28/Study Termination. (NCT01652729)
Timeframe: Baseline to Week 28

Change in Body Composition

Change in Body Mass Index (BMI)

Change in Total Daily Dose of Insulin (TDI) Per kg

Change in Waist Circumference

Change in Blood Pressure

Change in Hemoglobin A1c From Baseline to 26 Weeks, Adjusted for Baseline Hemoglobin A1c.

Hemoglobin A1c is a measure of glycemic control over approximately the past 3 months (NCT01881828)
Timeframe: 0-26 weeks

Change in Hemoglobin A1c From Baseline to 26 Weeks, Adjusted for Baseline Hemoglobin A1c.

Hemoglobin A1c is a measure of glycemic control over approximately the past 3 months (NCT01881828)
Timeframe: 0-26 weeks

Change in Serum Lipids

Flow Mediated Dilation - Endothelial Function

brachial artery ultrasonography % flow-mediated dilatation (FMD) for assessing endothelial function before and after an insulin clamp to assess insulin's effect on the vasculature (NCT02633488)
Timeframe: before and after 12 weeks on placebo or metformin

Change From Baseline in Adiponectin

The change between Adiponectin collected at final visit or week 24 and Adiponectin collected at baseline. (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Fasting Insulin

The change between the Fasting Insulin value collected at final visit or week 24 and Fasting Insulin collected at baseline. (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Fasting Plasma Glucose

The change between the value of Fasting Plasma Glucose collected at final visit or week 24 and Fasting Plasma Glucose collected at baseline. (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in High-Density Lipoprotein Cholesterol

The change between High-Density Lipoprotein Cholesterol collected at final visit or week 24 and High-Density Lipoprotein Cholesterol collected at baseline. (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Homeostasis Model Assessment - Insulin Resistance

The change between Homeostasis Model Assessment of Insulin Resistance collected at final visit or week 24 and Homeostasis Model Assessment of Insulin Resistance collected at baseline. Homeostasis Model Assessment measures insulin resistance, calculated by insulin times glucose, divided by a constant (22.5). (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Intermediate-Density Low Density Lipoprotein Concentration

The change between Intermediate-Density Low Density Lipoprotein collected at final visit or week 24 and Intermediate-Density Low Density Lipoprotein collected at baseline (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Intermediate-Medium High Density Lipoprotein (H3) Concentration

The change between Intermediate-Medium High Density Lipoprotein collected at final visit or week 24 and Intermediate-Medium High Density Lipoprotein collected at baseline (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Large High Density Lipoprotein (H4+H5) Concentration

The change between Large High Density Lipoprotein collected at final visit or week 24 and Large High Density Lipoprotein collected at baseline (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Large Low Density Lipoprotein (L3) Concentration

The change between Large Low Density Lipoprotein collected at final visit or week 24 and Large Low Density Lipoprotein collected at baseline. (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Large-Chylomicrons Very Low Density Lipoprotein Concentration

The change between Large-Chylomicrons Very Low Density Lipoprotein collected at final visit or week 24 and Large-Chylomicrons Very Low Density Lipoprotein collected at baseline (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Low-Density Lipoprotein Cholesterol

The change between Low-Density Lipoprotein Cholesterol collected at final visit or week 24 and Low-Density Lipoprotein Cholesterol collected at baseline. (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Mean High Density Lipoprotein Particle Concentration

The change between High Density Lipoprotein collected at final visit or week 24 and High Density Lipoprotein collected at baseline. (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Mean High Density Lipoprotein Particle Size

The change between High Density Lipoprotein collected at final visit or week 24 and High Density Lipoprotein collected at baseline. (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Mean Low Density Lipoprotein Particle Concentration

The change between Low Density Lipoprotein particle concentration collected at final visit or week 24 and Low Density Lipoprotein particle concentration collected at baseline. (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Mean Low Density Lipoprotein Particle Size

The change between Low Density Lipoprotein collected at final visit or week 24 and Low Density Lipoprotein collected at baseline. (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Mean Very Low Density Lipoprotein Particle Concentration

The change between Very Low Density Lipoprotein collected at final visit or week 24 and Very Low Density Lipoprotein collected at baseline. (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Mean Very Low Density Lipoprotein Particle Size

The change between Very Low Density Lipoprotein collected at final visit or week 24 and Very Low Density Lipoprotein collected at baseline. (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Medium-Intermediate Very Low Density Lipoprotein (V3+V4) Concentration

The change between Medium-Intermediate Very Low Density Lipoprotein collected at final visit or week 24 and Medium-Intermediate Very Low Density Lipoprotein collected at baseline (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Medium-Small Low Density Lipoprotein Concentration

The change between Medium-Small Low Density Lipoprotein collected at final visit or week 24 and Medium-Small Low Density Lipoprotein collected at baseline (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Small High Density Lipoprotein (H1+H2) Concentration

The change between Small High Density Lipoprotein collected at final visit or week 24 and Small High Density Lipoprotein collected at baseline (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Small Low Density Lipoprotein Concentration

The change between Small Low Density Lipoprotein collected at final visit or week 24 and Small Low Density Lipoprotein collected at baseline (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Small Very Low Density Lipoprotein (V1+V2) Concentration

The change between Small Very Low Density Lipoprotein collected at final visit or week 24 and Small Very Low Density Lipoprotein collected at baseline (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Total Cholesterol

The change between Total Cholesterol collected at final visit or week 24 and Total Cholesterol collected at baseline. (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Triglycerides

The change between Triglycerides collected at final visit or week 24 and Triglycerides collected at baseline. (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Very Small Low Density Lipoprotein Concentration

The change between Very Small Low Density Lipoprotein collected at final visit or week 24 and Very Small Low Density Lipoprotein collected at baseline (NCT00727857)
Timeframe: Baseline and Week 24

Median Percent Change From Baseline in High Sensitivity C-reactive Protein

Measurement for High Sensitivity C-reactive Protein was collected at final visit or week 24 and at baseline. Percent change from baseline is calculated as: [(Week 24 - baseline levels)/baseline]*100 (NCT00727857)
Timeframe: Baseline and Week 24

Percent Change From Baseline in Glycosylated Hemoglobin

The change between the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at final visit or week 24 and Glycosylated Hemoglobin collected at baseline. (NCT00727857)
Timeframe: Baseline and Week 24

Change From Baseline in Body Fat

Body fat is reported as a percentage of body weight. (NCT00443755)
Timeframe: Baseline, 3 months

Change From Baseline in Body Mass Index

Body Mass Index (BMI) is a health index for comparing weight to height. BMI is a person's weight in kilograms (kg) divided by his or her height in meters squared. The body mass index is an indication if a person is at a suitable weight for his height on an approximation of body fat. (NCT00443755)
Timeframe: Baseline, 3 months

Change From Baseline in Fasting Blood Glucose Level

Glucose (sugar) was measured in the blood and reported in milligrams per deciliter (mg/dL). (NCT00443755)
Timeframe: Baseline, 3 months

Change From Baseline in Fat-Free Mass (FFM)

FFM was measured using dual energy x-ray absorptiometry (DEXA) scans and is reported in kilograms (kg). (NCT00443755)
Timeframe: Baseline, 3 months

Change From Baseline in Glycosylated Hemoglobin (HbA1c)

HbA1c is a measure of average blood sugar levels over the preceding 3 month period. HbA1c was measured by ion-exchange chromatography and reported as a percentage. (NCT00443755)
Timeframe: Baseline, 3 months

Change From Baseline in Inflammatory Biomarker Tumor Necrosis Factor-alpha (TNF-α)

TNF-α is an inflammatory cytokine and is reported in picograms/milliliter (pg/mL). (NCT00443755)
Timeframe: Baseline, 3 month

Change From Baseline in Insulin Levels

Insulin levels in the blood were measured by immunoenzymatic assay and reported in micro International Units per milliliter (mcIU/mL). (NCT00443755)
Timeframe: Baseline, 3 months

Change From Baseline in Insulin Sensitivity as Measured by Glucose Infusion Rate (GIR)

Insulin sensitivity was measured the morning after an overnight fast during an in-patient stay in the Clinical Research Unit & was determined by the mean GIR necessary to maintain euglycemia during a hyperinsulinemic (1.5 mcIU/kg of FFM per minute)-euglycemic (85-95 mg/dL) clamp. The clamp is an 8 hour process where a hand vein is catheterized to collect blood samples and intravenous lines are used to infuse glucose, saline, insulin, phenylalanine and amino acid solutions at at pre-specified times/rates. The mean GIR was calculated as the rate per kilograms of fat-free mass (FFM) during 4 hours of steady-state (hours 4-8 of the 8 hour clamp) reported as micromols/kilogram of FFM per minute. The FFM was measured by dual-energy x-ray absorptiometry (DEXA) scan. Insulin was infused with 5% essential amino acid solution (3mL/kg of FFM/hour) to prevent the insulin-dependent decrease of amino acids during insulin infusion. (NCT00443755)
Timeframe: Baseline, 3 months

Change From Baseline in the Inflammatory Biomarker Adiponectin

Adiponectin is an anti-inflammatory cytokine and is reported in milligrams per milliliter (mg/mL). (NCT00443755)
Timeframe: Baseline, 3 months

Change From Baseline in the Inflammatory Biomarker C-Reactive Protein (CRP)

CRP is an inflammatory cytokine and is reported in milligrams per deciliter (mg/dL). (NCT00443755)
Timeframe: Baseline, 3 months

Change From Baseline in the Inflammatory Biomarker Interleukin 6 (IL-6)

IL-6 is an inflammatory cytokine and reported in picograms per deciliter (pg/dL). (NCT00443755)
Timeframe: Baseline, 3 months

Change From Baseline in the Thrombotic Biomarker Fibrinogen

Fibrinogen was measured by thrombin clotting rate assay (Beckman Coulter, Inc. Brea, California) and reported in milligrams/deciliter (mg/dL). (NCT00443755)
Timeframe: Baseline, 3 months

Change From Baseline in the Thrombotic Biomarker Plasminogen Activator Inhibitor-1 (PAI-1)

PAI-1 was measured by enzyme-linked immunosorbent assay (Diagnostica Stago Inc., Parsippany, New Jersey) and reported in nanograms per milliliter (ng/mL). (NCT00443755)
Timeframe: Baseline, 3 months

Change From Baseline in Lipid Profile

Change in lipids were measured by the change from baseline to 3 months of triglycerides, high-density lipoprotein cholesterol (HDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). All were reported in milligrams/deciliter (mg/dL). (NCT00443755)
Timeframe: Baseline, 3 months

Comparison of Changes in Fasting Serum Glucose (FSG)With Pioglitazone and Metformin

Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin. (NCT01589445)
Timeframe: 3 months for each drug

Comparison of Changes in Fasting Serum Insulin (FSI)With Pioglitazone and Metformin

Comparison of Changes in Glycosylated Hemoglobin (HbA1c)With Pioglitazone and Metformin

Comparison of Changes in HOMA Percent B and HOMA Percent S With Pioglitazone and Metformin

"Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin.~Analysis 1: Homeostatic Model Assessment of Beta cell function(HOMA percent B) Analysis 2: Homeostatic Model Assessment of Insulin Sensitivity (Homa percent S)" (NCT01589445)
Timeframe: 3 months for each drug

Comparison of Changes in Insulin Levels (HOMA IR,QUICKI) With Pioglitazone and Metformin

"Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin.~Analysis 1: Homeostasis Model Assessment Insulin Resistance(HOMA IR) Analysis 2: Quantitative Insulin sensitivity Check Index(QUICKI)" (NCT01589445)
Timeframe: 3 months for each drug

Comparison of Changes in Lipid Profiles With Pioglitazone and Metformin

"Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin.~Analysis 1:Total Cholesterol(TC) Analysis 2:Triglyceride(TG) Analysis 3:High Density Lipoprotein(HDL) Analysis 4:Low Density Lipoprotein(LDL)" (NCT01589445)
Timeframe: 3 months for each drug

Pharmacokinetics Parameter

Area Under Curve from 0 to 72 hours (AUCt) (NCT04964193)
Timeframe: before dosing (0 h) and at 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 15, 24, 36, 48 and 72 hours after dosing

Pharmacokinetics Parameter

Maximum plasma concentration (Cmax) (NCT04964193)
Timeframe: before dosing (0 h) and at 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 15, 24, 36, 48 and 72 hours after dosing

Independent Re-adjudication (IR) Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Original RECORD Endpoint Definitions

IR was based on original RECORD endpoint definitions. CV death= no unequivocal non-CV cause (sudden death, death from acute vascular events, heart failure, acute MI, other CV causes, and deaths adjudicated as unknown cause). MI event=hospitalization + elevation of specific cardiac biomarkers above the upper limit of normal + cardiac ischemia symptoms/new pathological electrocardiogram findings. Stroke event=hospitalization + rapidly developed clinical signs of focal/global disturbance of cerebral function for more than 24 hours, with no apparent cause other than a vascular origin. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Independent Re-adjudication Outcome: Number of Participants (Par.) With an Event of Stroke (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions

Par. with a stroke (fatal or non-fatal) event as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. A stroke event=hospitalization plus rapidly developed clinical signs of focal (or global) disturbance of cerebral function lasting more than 24 hours (unless interrupted by thrombolysis, surgery, or death), with no apparent cause other than a vascular origin, including par. presenting clinical signs/symptoms suggestive of subarachnoid haemorrhage/intracerebral haemorrhage/cerebral ischemic necrosis or cause of death adjudicated as stroke. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Independent Re-adjudication Outcome: Number of Participants Who Died Due to Any Cause

All deaths identified during the original record study and discovered after the re-adjudication efforts began were included. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Contemporary Endpoint Definitions

The number of participants with a CV (or unknown) death as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. CV death included death resulting from an acute myocardial infarction (MI), sudden cardiac death, death due to heart failure, death due to stroke, and death due to other CV causes. Deaths of unknown cause were counted as CV deaths. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Independent Re-adjudication Outcome: Number of Participants With a CV (or Unknown) Death, Based on Original RECORD Endpoint Definitions

"The number of participants with a CV death (or unknown) as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. CV death was defined as any death for which an unequivocal non-CV cause could not be established. CV death included death following heart failure, death following acute myocardial infarction (MI), sudden death, death due to acute vascular events, and other CV causes. Deaths due to unknown causes were classified as unknown deaths, but were counted as CV deaths for the analysis of this endpoint." (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Independent Re-adjudication Outcome: Number of Participants With a First Occurrence of a Major Adverse Cardiovascular Event (MACE) Defined as CV (or Unknown) Death, Non-fatal MI, and Non-fatal Stroke Based on Contemporary Endpoint Definitions

Independent re-adjudication was based on the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions. CV death included death resulting from an acute MI; sudden cardiac death and death due to heart failure, stroke, and to other CV causes. Deaths of unknown cause were counted as CV deaths. MI was defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Stroke was defined as an acute episode of neurological dysfunction caused by focal or global brain, spinal cord, or retinal vascular injury. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions

The number of participants with an MI (fatal or non-fatal) event as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. An event of MI was defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Independent Re-adjudication Outcome: Number of Participants With an Event of Myocardial Infarction (Fatal and Non-fatal), Based on Original RECORD Endpoint Definitions

The number of participants with an MI (fatal or non-fatal) event as determined by independent re-adjudication using the original RECORD endpoint definitions was recorded. An event of MI was defined as hospitalization plus elevation of cardiac biomarkers troponin (TN) I and/or TNT above the upper limit of normal (ULN) or creatinine kinase (CK) MB (M=muscle type; B=brain type) isoenzyme >= 2x the ULN or CK > 2x the ULN plus typical symptoms of cardiac ischemia or new pathological electrocardiogram findings, or cause of death adjudicated as MI. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Independent Re-adjudication Outcome: Number of Participants With an Event of Stroke (Fatal and Non-fatal), Based on Contemporary Endpoint Definitions

The number of participants with a stroke (fatal or non-fatal) event as determined by independent re-adjudication using the Standard Data Collection for Cardiovascular Trials Initiative (draft October 2011) endpoint definitions was recorded. An event of stroke was defined as an acute episode of neurological dysfunction caused by focal or global brain, spinal cord, or retinal vascular injury. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Model Adjusted Change From Baseline in Alanine Aminotransferase at Month 60

Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in alanine aminotransferase was calculated as the value at Month 60 minus the Baseline value. (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

Model Adjusted Change From Baseline in Body Weight at Month 60

Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in body weight was calculated as the value at Month 60 minus the Baseline value. (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

Model Adjusted Change From Baseline in Fasting Plasma Glucose at Month 60

Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in fasting plasma glucose was calculated as the value at Month 60 minus the Baseline value. (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment period

Model Adjusted Change From Baseline in HbA1c at Month 60

Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in HbA1c was calculated as the value at Month 60 minus the Baseline value. (NCT00379769)
Timeframe: Baseline and Month 60 of randomised dual therapy treatment period

Model Adjusted Change From Baseline in Waist Circumference at Month 60

Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in waist circumference was calculated as the value at Month 60 minus the Baseline value. (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Apolipoprotein B (Apo-B) at Month 60

The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in Apo-B was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]). (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment period

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for C-Reactive Protein at Month 60

The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in C-Reactive Protein was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]). (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Fibrinogen at Month 60

The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in fibrinogen was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]). (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Plasminogen Activator Inhibitor-1 (PAI-1) Antigen at Month 60

The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in plasminogen activator inhibitor-1 (PAI-1) antigen was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]). (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Urinary Albumin Creatinine Ratio at Month 60

The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in urinary albumin creatinine ratio was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]). (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

Number of Participants With an Event of Death Due to a Bone Fracture-related Event: Main Study + Observational Follow-up Combined

Number of Participants With Cardiovascular Death/Cardiovascular Hospitalisation Events

The number of participants with cardiovascular death events (death due to cardiovascular causes or deaths with insufficient information to rule out a cardiovascular cause) and cardiovascular hospitalisation events (hospitalisation for a cardiovascular event, excluding planned admissions not associated with a worsening of the disease/condition of the participant) was recorded. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Number of Participants With First Cardiovascular Hospitalisations/Cardiovascular Deaths by Stratum

Participants with first cardiovascular death (death due to cardiovascular causes or deaths with insufficient information to rule out a cardiovascular cause) and cardiovascular hospitalisation (hospitalisation for a cardiovascular event, excluding planned admissions not associated with a worsening of the disease/condition of the participant) were recorded by study stratum. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Number of Participants With Glycaemic Failure Events

Failure of glycaemic control was defined as two consecutive HbA1c values of ≥8.5 percent, or HbA1c ≥8.5percent at a single visit, after which the subject was either moved to the post-randomised treatment phase or triple therapy was started. (NCT00379769)
Timeframe: Baseline through to end of randomised dual therapy

The Number of Participants Starting Insulin at Any Time During the Study

The number of participants starting insulin at any time during the study was recorded. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Model Adjusted Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Month 60

Model adjusted (adjusted for any imbalances in the baseline values between within treatment groups) change from baseline in SBP and DBP was calculated as the value at Month 60 minus the Baseline value. (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

Model Adjusted Mean Change From Baseline in Insulin and Pro-insulin at Month 60

Model adjusted (adjusted for any imbalances in the baseline values between within stratum treatment groups) change from baseline in insulin and pro-insulin was calculated as the value at Month 60 minus the Baseline value. (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment period

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC), Low-density Lipoprotein (LDL) Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Triglycerides, and Free Fatty Acids (FFAs) at Month 60

The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in TC, LDL cholesterol, HDL cholesterol, triglycerides, and FFAs was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]). (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

Model Adjusted Ratio to Baseline (Expressed as a Percentage) for Total Cholesterol (TC):High-density Lipoprotein (HDL) Cholesterol and Low-density Lipoprotein (LDL) Cholesterol:HDL Cholesterol Ratios at Month 60

The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in TC:HDL cholesterol and LDL cholesterol:HDL cholesterol was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]). (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment period

Model Adjusted Ratio to Baseline (Expressed as a Percentage) Homeostasis Model Assessment (HOMA) Beta Cell Function and Insulin Sensitivity at Month 60

The model adjusted (adjusted for any imbalances in the baseline [BL] values between within stratum treatment groups) ratio to BL in HOMA beta-cell function and insulin sensitivity was calculated as the ratio of the Month 60 value to the BL value and was expressed as percent change from BL. For each treatment group, the model-adjusted mean change from BL at Month 60 was determined on the log scale. This mean was then back transformed to give a geometric mean (GM) of the ratio of the Month 60 value to BL on the original scale. The GM was expressed as a percentage (100*[GM^-1]). (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment phase

Number of Bone Fracture Events With the Indicated Outcome: Main Study + Observational Follow-up Combined

"The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The indicated fracture outcome was pre-specified in the CRF and included Unknown as a category. Fracture events with missing outcome data were reported as Data unavailable." (NCT00379769)
Timeframe: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)

Number of Bone Fracture Events With the Indicated Outcome: Observational Follow-up

"The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The indicated fracture outcome was pre-specified in the CRF and included Unknown as a category. Fracture events with missing outcome data were reported as Data unavailable." (NCT00379769)
Timeframe: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)

Number of HbA1c and Fasting Plasma Glucose (FPG) Responders at Month 60

Number of responders, i.e., participants meeting glycaemic targets (HbA1c less than or equal to 7 percent, FPG less than or equal to 7 mmol/L) (NCT00379769)
Timeframe: Baseline to Month 60 of the randomised dual therapy treatment period

Number of Participants Who Died Due to the Indicated Cancer-related Event: Main Study + Observational Follow-up Combined

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. (NCT00379769)
Timeframe: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)

Number of Participants Who Died Due to the Indicated Cancer-related Event: Observational Follow-up

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. (NCT00379769)
Timeframe: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)

Number of Participants With a Bone Fracture Event - Overall and by Gender: Main Study and Observational Follow-up Combined

Number of Participants With a Bone Fracture Event - Overall and by Gender: Observational Follow-up

Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Main Study + Observational Follow-up Combined

The OFU was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. (NCT00379769)
Timeframe: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)

Number of Participants With a Bone Fracture Event Reported as the Indicated Serious Adverse Event (by Higher Level Group Term) or Death: Observational Follow-up

The OFU was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. (NCT00379769)
Timeframe: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)

Number of Participants With Addition of Third Oral Agent/Switch to Insulin

The number of participants with addition of a third oral agent or switch to insulin from randomised dual combination treatment were recorded. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Number of Participants With Bone Fracture Events of the Indicated Cause: Main Study + Observational Follow-up Combined

Number of Participants With Bone Fracture Events of the Indicated Cause: Observational Follow-up

"The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The indicated fracture outcome was pre-specified in the CRF and included Unknown as a category. Fracture events with missing outcome data were reported as Data unavailable." (NCT00379769)
Timeframe: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)

Number of Participants With Cardiovascular Events and All-cause Deaths

Composites of participants with first cardiovascular (CV) hospitalisations and CV death or all-cause death and individual first events of acute myocardial infarction (MI) , stroke, congestive heart failure (CHF), CV death, and all-cause death. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Number of Participants With CV/Microvascular Events

The number of participants with first cardiovascular or microvascular events (renal, foot, eye) were recorded. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Number of Participants With Potentially High Morbidity Fracture Events and Non-high Morbidity Fracture Events, in Participants With Prior Hand/Upper Arm/Foot Fractures (H/UA/FF): Main Study + Observational Follow-up Combined

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The following bone fractures were grouped and were identified as potentially high morbidity bone fractures: hip, pelvis, upper leg, vertebral (lumbar spine, thoracic spine, cervical spine, spine - site unknown). (NCT00379769)
Timeframe: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)

Number of Participants With Potentially High Morbidity Fractures: Main Study + Observational Follow-up Combined

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. A bone fracture event is defined as one or more fractured bones occurring on the same date and that had the same Higher Level Group Term (HLGT) for fracture location, per participant. The following bone fractures were grouped and were identified as potentially high morbidity bone fractures: hip, pelvis, upper leg, vertebral (lumbar spine, thoracic spine, cervical spine, spine - site unknown). (NCT00379769)
Timeframe: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)

Number of Participants With the Indicated Bone Fracture by Fracture Site: Main Study + Observational Follow-up Combined

Number of Participants With the Indicated Bone Fracture by Fracture Site: Observational Follow-up

Number of Participants With the Indicated Serious Adverse Event: Observational Follow-up

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. (NCT00379769)
Timeframe: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)

Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Main Study + Observational Follow-up Combined

The observational follow-up (OFU) was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. The neoplasms/cancer events of bladder, breast, colon, liver, pancreatic, prostate cancer, and melanoma were pre-specified as cancers of interest for the OFU. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. (NCT00379769)
Timeframe: From the beginning of the main study through the end of the observational follow-up (up to 11.4 years)

Number of Participants With the Indicated Type of Malignant Neoplasms/Cancer Events Reported as an SAE or Death by Location (Including Location of Special Interest): Observational Follow-up

The observational follow-up (OFU) was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the OFU. The neoplasms/cancer events of bladder, breast, colon, liver, pancreatic, prostate cancer, and melanoma were pre-specified as cancers of interest for the OFU. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. (NCT00379769)
Timeframe: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)

Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Main Study + Observational Follow-up Combined

Number of Participants With the Indicated Type of Neoplasm/Cancer Event Reported as a Serious Adverse Event (SAE) or Death: Observational Follow-up

The observational follow-up was designed to collect data concerning cancer and bone fractures in RECORD participants during a 4-year period after the end of the main RECORD study. At the end of the main study, all study medication was stopped. Participants were not provided with study medication in the observational follow-up; instead, anti-diabetic treatment was prescribed at the investigator's discretion. An SAE is defined as any event that is fatal; life threatening; disabling/incapacitating; results in hospitalization (excluding elective surgery or routine clinical procedures); prolongs a hospital stay; is associated with a congenital abnormality; cancer; is associated with an overdose. In addition, any event that the investigator regards as serious or that would suggest any significant hazard, contraindication, side effect, or precaution that may be associated with the study procedures should be reported as an SAE. (NCT00379769)
Timeframe: From the end of the RECORD study through the end of the observational follow-up (up to 4.0 years)

Total Number of Cardiovascular Hospitalisations and Cardiovascular Deaths

The total number of events for individual components of cardiovascular (CV) hospitalisations and cardiovascular deaths were recorded. MI, myocardial infarction. (NCT00379769)
Timeframe: Baseline through End of Study (up to 7.5 years)

Percent Change in Triglyceride (TG) Levels Post Treatment

The reported percent change is the difference between TG levels obtained on initial visit (day 0) and TG levels obtained at final visit (week 12) as per protocol (NCT00819910)
Timeframe: 12 weeks from initial visit (day 0) to final visit (12 weeks)

Post-treatment Percent Change in High-Density Lipoprotein (HDL) Levels

The reported percent change is the difference between HDL levels obtained on initial visit (day 0) and HDL levels obtained at final visit (week 12) as per protocol (NCT00819910)
Timeframe: 12 weeks from initial visit (day 0) to final visit (12 weeks)

Post-treatment Percent Change in Low-Density Lipoprotein (LDL) Levels

The reported percent change is the difference between LDL levels obtained on initial visit (day 0) and LDL levels obtained at final visit (week 12) as per protocol (NCT00819910)
Timeframe: 12 weeks from initial visit (day 0) to final visit (12 weeks)

Mean Levels of Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) at Initial Visit and Final Visit

The mean Levels of AST and ALT measured at initial visit (Day 0) and final visit (Week 12) annotated as AST 1, AST 12, and ALT 1 and ALT 12, respectively. (NCT00819910)
Timeframe: 12 weeks from initial visit (day 0) to final visit (12 weeks)

Post-treatment Percent Change in Apolipoprotein A-I (Apo AI), Apolipoprotein A-II (Apo AII) and Apolipoprotein C-III (Apo CIII) Levels

Post-treatment median change in Apo AI, Apo AII and Apo CIII levels reported in mg/dL with Interquartile ranges provided (NCT00819910)
Timeframe: 12 weeks from initial visit (day 0) to final visit (12 weeks)

Intervention	mg/dL (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-28.63
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-28.97
Placebo (Overall Cardiovascular Study)	-8.76

Intervention	A1C Percentage (Least Squares Mean)
Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	-0.77
Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	-0.84
Placebo (Ins+/-Met Sub-study)	-0.19

Intervention	A1C Percentage (Least Squares Mean)
Ertugliflozin 5 mg (Metformin With Sulfonylurea Glycemic Sub-study)	-0.89
Ertugliflozin 15 mg (Metformin With Sulfonylurea Glycemic Sub-study)	-0.98
Placebo (Metformin With Sulfonylurea Glycemic Sub-study)	-0.23

Intervention	A1C Percentage (Least Squares Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-0.70
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-0.72
Placebo (Overall Cardiovascular Study)	-0.22

Intervention	A1C Percentage (Least Squares Mean)
Ertugliflozin 5 mg (Sulfonylurea Monotherapy Glycemic Sub-Study)	-0.91
Ertugliflozin 15 mg (Sulfonylurea Monotherapy Glycemic Sub-Study)	-0.78
Placebo (Sulfonylurea Monotherapy Glycemic Sub-Study)	-0.56

Intervention	Units/Day (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	0.45
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-1.58
Placebo (Overall Cardiovascular Study)	6.16

Intervention	Units/Day (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	1.64
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-1.92
Placebo (Overall Cardiovascular Study)	7.99

Intervention	Units/Day (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	2.96
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-1.87
Placebo (Overall Cardiovascular Study)	7.28

Intervention	Units/Day (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-2.47
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-1.77
Placebo (Overall Cardiovascular Study)	9.42

Intervention	Units/Day (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	1.05
Ertugliflozin 15 mg (Overall Cardiovascular Study)	0.81
Placebo (Overall Cardiovascular Study)	3.71

Intervention	Units/Day (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	0.84
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-1.69
Placebo (Overall Cardiovascular Study)	5.57

Intervention	mg/dL (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	0.024
Ertugliflozin 15 mg (Overall Cardiovascular Study)	0.035
Placebo (Overall Cardiovascular Study)	0.034

Intervention	mg/dL (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	0.037
Ertugliflozin 15 mg (Overall Cardiovascular Study)	0.035
Placebo (Overall Cardiovascular Study)	0.049

Intervention	mg/dL (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	0.032
Ertugliflozin 15 mg (Overall Cardiovascular Study)	0.036
Placebo (Overall Cardiovascular Study)	0.059

Intervention	mg/dL (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	0.027
Ertugliflozin 15 mg (Overall Cardiovascular Study)	0.042
Placebo (Overall Cardiovascular Study)	0.098

Intervention	mg/dL (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-0.034
Ertugliflozin 15 mg (Overall Cardiovascular Study)	0.001
Placebo (Overall Cardiovascular Study)	-0.013

Intervention	mg/dL (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	0.022
Ertugliflozin 15 mg (Overall Cardiovascular Study)	0.032
Placebo (Overall Cardiovascular Study)	-0.002

Intervention	mg/dL (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	0.013
Ertugliflozin 15 mg (Overall Cardiovascular Study)	0.023
Placebo (Overall Cardiovascular Study)	0.004

Intervention	mmHg (Least Squares Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-0.94
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-0.90
Placebo (Overall Cardiovascular Study)	-0.23

Intervention	mmHg (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-1.27
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-0.92
Placebo (Overall Cardiovascular Study)	-0.22

Intervention	mmHg (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-1.45
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-1.42
Placebo (Overall Cardiovascular Study)	-0.64

Intervention	mmHg (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-1.82
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-1.43
Placebo (Overall Cardiovascular Study)	-1.26

Intervention	mmHg (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-2.18
Ertugliflozin 15 mg (Overall Cardiovascular Study)	1.86
Placebo (Overall Cardiovascular Study)	7.29

Intervention	mmHg (Least Squares Mean)
Ertugliflozin 5 mg (Insulin +/- Metformin Glycemic Sub-study)	-0.86
Ertugliflozin 15 mg (Insulin +/- Metformin Glycemic Sub-study)	-0.64
Placebo (Insulin +/- Metformin Glycemic Sub-study)	-0.26

Intervention	mmHg (Least Squares Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-0.99
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-1.08
Placebo (Overall Cardiovascular Study)	-0.12

Intervention	mmHg (Least Squares Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-0.97
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-0.95
Placebo (Overall Cardiovascular Study)	-0.15

Intervention	mmHg (Least Squares Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-1.80
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-1.82
Placebo (Overall Cardiovascular Study)	0.90

Intervention	mmHg (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-1.55
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-1.21
Placebo (Overall Cardiovascular Study)	0.84

Intervention	mmHg (Least Squares Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	-2.07
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-2.26
Placebo (Overall Cardiovascular Study)	0.53

Intervention	mmHg (Mean)
Ertugliflozin 5 mg (Overall Cardiovascular Study)	1.28
Ertugliflozin 15 mg (Overall Cardiovascular Study)	-3.46
Placebo (Overall Cardiovascular Study)	2.72