2,4-thiazolidinedione and Diabetes Mellitus, Adult-Onset studies

thiazolidine-2,4-dione: structure in first source
1,3-thiazolidine-2,4-dione : A thiazolidenedione carrying oxo substituents at positions 2 and 4.

Research Excerpts

Excerpt	Relevance	Reference
"In T2D patients with ischemic stroke, lobeglitazone reduced the risk of cardiovascular complications similar to that of pioglitazone without an increased risk of HF."	8.31	Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study. ( Baik, M; Jeon, J; Kim, J; Yoo, J, 2023)
"To compare the risks of hospitalization for heart failure (HHF) associated with sulfonylurea (SU), dipeptidyl peptidase-4 inhibitor (DPP-4i), and thiazolidinedione (TZD) as add-on medications to metformin (MET) therapy using the data of Korean adults with type-2 diabetes from the Korean National Health Insurance database."	7.91	Second-line glucose-lowering drugs added to metformin and the risk of hospitalization for heart failure: A nationwide cohort study. ( Ha, KH; Kim, DJ; Kim, HC; Lee, H; Lee, JH; Lee, SJ, 2019)
"Genetic variation at the NFATC2 locus contributes to edema among individuals who receive rosiglitazone."	7.76	Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. ( Anand, S; Bailey, SD; Diaz, R; Do, R; Engert, JC; Gerstein, HC; Keavney, B; Mohan, V; Montpetit, A; Xie, C; Yusuf, S, 2010)
" The use of dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, thiazolidinedione, and sulfonylurea was associated with a decreased risk of dementia in comparison to no treatment with antidiabetic agents (hazard ratio [HR] for DPP-4 inhibitors, 0."	5.05	Impact of antidiabetic agents on dementia risk: A Bayesian network meta-analysis. ( Han, M; Simó, R; Tang, X; Yang, J; Zhou, JB, 2020)
" Nine of the eleven studies showed significant decrease in body weight among participants in the exenatide group compared with placebo or control group while the other two studies did not report statistically significant differences in body weight."	4.93	The Use of Exenatide in Managing Markers of Cardiovascular Risk in Patients with Type 2 Diabetes: A Systematic Review. ( Ojo, O, 2016)
"Both metformin and thiazolidinedione derivatives(TZDs) improve insulin resistance, a major pathogenesis of type 2 diabetes, and decrease blood glucose levels without stimulating insulin secretion."	4.82	[Insulin-sensitizing agents: metformin and thiazolidinedione derivatives]. ( Satoh, J, 2003)
"In T2D patients with ischemic stroke, lobeglitazone reduced the risk of cardiovascular complications similar to that of pioglitazone without an increased risk of HF."	4.31	Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study. ( Baik, M; Jeon, J; Kim, J; Yoo, J, 2023)
"To compare the risks of hospitalization for heart failure (HHF) associated with sulfonylurea (SU), dipeptidyl peptidase-4 inhibitor (DPP-4i), and thiazolidinedione (TZD) as add-on medications to metformin (MET) therapy using the data of Korean adults with type-2 diabetes from the Korean National Health Insurance database."	3.91	Second-line glucose-lowering drugs added to metformin and the risk of hospitalization for heart failure: A nationwide cohort study. ( Ha, KH; Kim, DJ; Kim, HC; Lee, H; Lee, JH; Lee, SJ, 2019)
"The aim of the present study was to assess the risk of overall mortality, coronary artery disease (CAD), and congestive heart failure (CHF) in patients with type 2 diabetes mellitus (T2DM) treated with metformin (MF) and an additional antidiabetic agent."	3.83	Risk of overall mortality and cardiovascular events in patients with type 2 diabetes on dual drug therapy including metformin: A large database study from the Cleveland Clinic. ( Kannan, S; Karafa, M; Matsuda, S; Pantalone, KM; Wells, BJ; Zimmerman, RS, 2016)
"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)
"Genetic variation at the NFATC2 locus contributes to edema among individuals who receive rosiglitazone."	3.76	Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. ( Anand, S; Bailey, SD; Diaz, R; Do, R; Engert, JC; Gerstein, HC; Keavney, B; Mohan, V; Montpetit, A; Xie, C; Yusuf, S, 2010)
" When administered to diabetic KKAy mice, T2384 rapidly improved insulin sensitivity in the absence of weight gain, hemodilution, and anemia characteristics of treatment with rosiglitazone (a TZD)."	3.74	T2384, a novel antidiabetic agent with unique peroxisome proliferator-activated receptor gamma binding properties. ( Chen, JL; Escaron, P; Furukawa, N; Learned, RM; Lee, G; Li, Y; Lindstrom, M; Liu, J; Liu, X; Plotnikova, O; Prasad, V; Walker, N; Wang, Z; Weiszmann, J; Xu, H, 2008)
" We found that mice with CD knockout of this receptor were resistant to the rosiglitazone- (RGZ) induced increases in body weight and plasma volume expansion found in control mice expressing PPARgamma in the CD."	3.73	Collecting duct-specific deletion of peroxisome proliferator-activated receptor gamma blocks thiazolidinedione-induced fluid retention. ( Gonzalez, FJ; Kohan, DE; Nelson, RD; Yang, T; Zhang, A; Zhang, H, 2005)
"Combination of insulin and rosiglitazone is effective in massively obese patients with Type 2 diabetes, though there is a high incidence of peripheral oedema."	3.71	Combination of insulin and thiazolidinedione therapy in massively obese patients with Type 2 diabetes. ( Akarca, C; Barton, DM; Baskar, V; Buch, HN; Kamalakannan, D; Singh, BM, 2002)
"Pioglitazone treatment led to a significant 3% body mass increase."	2.90	Effect of pioglitazone treatment on brown adipose tissue volume and activity and hypothalamic gliosis in patients with type 2 diabetes mellitus: a proof-of-concept study. ( Cendes, F; Cintra, RM; de-Lima-Júnior, JC; Folli, F; Monfort-Pires, M; Rachid, B; Ramos, CD; Rodovalho, S; Van de Sande-Lee, S; Velloso, LA, 2019)
" 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)
"A total of 2368 patients with type 2 diabetes mellitus and clinically stable, angiographically documented coronary artery disease were randomized to treatment with 1 of the 2 strategies and followed for an average of 5 years."	2.76	Profibrinolytic, antithrombotic, and antiinflammatory effects of an insulin-sensitizing strategy in patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. ( Brooks, MM; Frye, RL; Genuth, S; Hardison, RM; Huber, K; Krishnaswami, A; McBane, RD; Pratley, RE; Schneider, DJ; Sobel, BE; Wolk, R, 2011)
" Adverse events for the US cohort were consistent with previously reported data from the 3 trials."	2.76	Efficacy and safety of saxagliptin combination therapy in US patients with type 2 diabetes. ( Allen, E; Chen, R; Donovan, M; Fleming, D; Karyekar, C; Ravichandran, S, 2011)
"Pioglitazone treatment improves insulin resistance (IR), glucose metabolism, hepatic steatosis, and necroinflammation in patients with nonalcoholic steatohepatitis (NASH)."	2.74	Importance of changes in adipose tissue insulin resistance to histological response during thiazolidinedione treatment of patients with nonalcoholic steatohepatitis. ( Balas, B; Belfort-Aguilar, R; Cusi, K; Gastaldelli, A; Hardies, LJ; Harrison, SA; Schenker, S, 2009)
"446), the addition of pioglitazone could significantly lower serum RBP4 and HOMA-IR values, whereas an increased dosage of sulfonylurea agents did not alter HOMA-IR, RBP4, or adiponectin in type 2 diabetic patients who had been treated with metformin and/or sulfonylurea."	2.73	Thiazolidinedione addition reduces the serum retinol-binding protein 4 in type 2 diabetic patients treated with metformin and sulfonylurea. ( Chang, YH; Hsiao, PJ; Li, TH; Lin, KD; Shin, SJ; Wang, CL; Yang, YH, 2008)
"The purpose of this study was to assess the efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor vildagliptin in combination with the thiazolidinedione (TZD) pioglitazone in patients with type 2 diabetes (T2DM)."	2.73	Vildagliptin in combination with pioglitazone improves glycaemic control in patients with type 2 diabetes failing thiazolidinedione monotherapy: a randomized, placebo-controlled study. ( Baron, MA; Dejager, S; Garber, AJ; Rochotte, E; Schweizer, A, 2007)
"The proposed novel type 2 diabetes subgroups provide an interesting concept that could lead to a better understanding of the pathophysiology of the broad group of type 2 diabetes, paving the way for personalised treatment choices based on understanding the root cause of the disease."	2.72	Type 2 diabetes subgroups and potential medication strategies in relation to effects on insulin resistance and beta-cell function: A step toward personalised diabetes treatment? ( Erazo-Tapia, E; Oscarsson, J; Schrauwen, P; Veelen, A, 2021)
"In patients with type 2 diabetes mellitus (T2DM), combination therapy is usually required to optimize glucose metabolism as well as to help patients achieve aggressive targets for low-density lipoprotein cholesterol (LDL-C) and other lipid parameters associated with cardiovascular risk."	2.71	Efficacy and safety of ezetimibe co-administered with simvastatin in thiazolidinedione-treated type 2 diabetic patients. ( Gaudiani, LM; Lewin, A; Meneghini, L; Mitchel, Y; Perevozskaya, I; Plotkin, D; Shah, S, 2005)
"The progressive nature of type 2 diabetes (T2D) requires practitioners to periodically evaluate patients and intensify glucose-lowering treatment once glycemic targets are not attained."	2.58	SGLT2 Inhibitors in Combination Therapy: From Mechanisms to Clinical Considerations in Type 2 Diabetes Management. ( IJzerman, RG; Muskiet, MHA; van Baar, MJB; van Bloemendaal, L; van Raalte, DH; van Ruiten, CC, 2018)
"While there was evidence that type 2 diabetes is associated with an increased risk of cancer, existing studies seemed insufficient to definitively demonstrate a link between cancer risk and use of specific anti-hyperglycemic therapies."	2.55	Cancer risks of anti-hyperglycemic drugs for type 2 diabetes treatment - a clinical appraisal. ( Kosiborod, M; Leiter, LA; Poulter, NR; Rajagopalan, S; Ray, K; Vora, J, 2017)
"Placebo-controlled randomized trials in type 2 diabetes patients with a study length ≥12 weeks were included."	2.53	Efficacy of hypoglycemic treatment in type 2 diabetes stratified by age or diagnosed age: a meta-analysis. ( Cai, X; Chen, Y; Gao, X; Han, X; Ji, L; Yang, W; Zhang, S; Zhou, L, 2016)
"Rivoglitazone has been shown, through small clinical studies, to decrease hemoglobin A(1c) (A1C) by 0."	2.49	Rivoglitazone: a new thiazolidinedione for the treatment of type 2 diabetes mellitus. ( Koffarnus, RL; Phillippe, HM; Wargo, KA, 2013)
"Vildagliptin is a potent and selective oral dipeptidyl peptidase-4 inhibitor that improves glycaemic control in patients with type 2 diabetes mellitus (T2DM) by increasing both alpha- and beta-cell responsiveness to glucose."	2.45	Translating science into clinical practice: focus on vildagliptin in combination with metformin. ( Barnett, AH, 2009)
"TZDs are approved for the treatment of Type 2 diabetes, and have been studied as a diabetes-prevention strategy."	2.44	Pharmacogenetics of thiazolidinedione therapy. ( Aquilante, CL, 2007)
"Type 2 diabetes is the most common cause of chronic renal failure worldwide."	2.44	Antiproteinuric and anti-inflammatory effects of thiazolidinedione. ( Li, PK; Szeto, CC, 2008)
" The sitagliptin dosage recommended by the manufacturer is 100 mg once daily as monotherapy or in combination with metformin or a thiazolidinedione."	2.44	Sitagliptin: a novel agent for the management of type 2 diabetes mellitus. ( Nogid, A; Pham, DQ; Plakogiannis, R, 2008)
"Worsening glycaemic control in type 2 diabetes mellitus relates to a decline in beta-cell function, associated with impaired negative feedback regulation of insulin release."	2.43	Potential role of oral thiazolidinedione therapy in preserving beta-cell function in type 2 diabetes mellitus. ( Lübben, G; Walter, H, 2005)
"Insulin resistance is defined as a state of subnormal biological response to normal quantity of insulin."	2.43	[Insulin resistance: the adipose tissue in the focus]. ( Urich, E, 2005)
"Type 2 diabetes mellitus is a major cause of morbidity and mortality worldwide, and the prevalence is set to increase dramatically over the coming decades."	2.43	Etiology of insulin resistance. ( Petersen, KF; Shulman, GI, 2006)
" As the prevalence of children diagnosed with type 2 diabetes continues to rise, the need for adequate information regarding the safety, efficacy, and appropriate dosing of oral diabetes medications in the pediatric population likewise increases."	2.43	The utility of oral diabetes medications in type 2 diabetes of the young. ( Abu-Baker, A; Busch, RS; Kane, MP, 2005)
"The incidence of obesity and type 2 diabetes mellitus (DM2) in the United States has been increasing dramatically over the past 15 years, and is now at epidemic proportions."	2.42	Cardiovascular implications of thiazolidinedione therapy. ( King, D; Lamb, RE, 2004)
"In patients with type 2 diabetes, early use of TZDs may be beneficial in both achieving glucose control and reducing the development or worsening of microalbuminuria or hypertension."	2.42	Hypertension and nephropathy. ( Bakris, GL, 2003)
"Treatment of the dyslipidemia associated with type 2 diabetes and FCHL with a combination of a statin and a thiazolidinedione or niacin offers the most comprehensive modality to correct the various lipid abnormalities."	2.42	Lipoprotein distribution in the metabolic syndrome, type 2 diabetes mellitus, and familial combined hyperlipidemia. ( Ayyobi, AF; Brunzell, JD, 2003)
"Current clinical management of type 2 diabetes is focused on treatment of the signs and symptoms of late-stage disease rather than addressing potential underlying causes, which may be amenable to currently available therapies, based on a broad understanding of existing data, practice experience, and rational speculation."	2.42	Pancreatic beta-cell loss and preservation in type 2 diabetes. ( Buchanan, TA, 2003)
"Type 2 diabetes is now a global epidemic, with the number of people affected worldwide predicted to more than double to 300 million by the year 2025."	2.42	Thiazolidinedione therapy: the benefits of aggressive and early use in type 2 diabetes. ( Gadsby, R; Reusch, JE, 2003)
"Insulin resistance is a characteristic feature of uremia."	2.42	Treatment of insulin resistance in uremia. ( Nesić, V; Stefanović, V; Stojimirović, B, 2003)
"Type 2 diabetes is a multiorgan disease that results from the combination of insulin resistance and a beta-cell secretory defect."	2.42	The need for reappraisal of type 2 diabetes mellitus management. ( Wyne, KL, 2003)
"Patients with type 2 diabetes frequently manifest multiple risk factors for cardiovascular morbidity and mortality."	2.42	Insulin resistance syndrome. Description, pathogenesis, and management. ( Miller, JL, 2003)
"With the understanding of type 2 diabetes mellitus constantly evolving, and with the introduction of many new agents during the past few years, it is often difficult to keep up to date with the management of type 2 diabetes."	2.42	Constructing an algorithm for managing type 2 diabetes. Focus on role of the thiazolidinediones. ( Bell, DS; Braunstein, S; Drexler, AJ; Miller, JL; Nuckolls, JG; Wyne, KL, 2003)
"Treatment options for type 2 diabetes mellitus currently consist of insulin sensitizers, alpha-glucosidase inhibitors, secretagogues, and insulin."	2.42	Type 2 diabetes mellitus: what is the optimal treatment regimen? ( Bell, DS, 2004)
"Patients with type 2 diabetes mellitus are at increased risk for postangioplasty restenosis, which results from excessive intimal hyperplasia."	2.42	Thiazolidinedione regulation of smooth muscle cell proliferation. ( Bruemmer, D; Law, RE, 2003)
"Type 2 diabetes mellitus is an increasingly prevalent disorder associated with multiple metabolic derangements."	2.42	Insulin sensitizers. ( Basu, A; Kudva, YC; Zangeneh, F, 2003)
"At the moment, they are indicated in type 2 diabetes but could be of interest in a broader array of diseases related to insulin resistance."	2.41	[Thiazolidinediones in type 2 diabetes. Role of peroxisome proliferator-activated receptor gamma (PPARgamma)]. ( Dubois, M; Pattou, F; Schoonjans, K; Vantyghem, MC, 2002)
"Insulin resistance is a fundamental feature of type 2 diabetes and is also associated with increased cardiovascular risk."	2.41	Insulin-sensitizing agents--thiazolidinediones (glitazones). ( Barnett, AH, 2002)
"The pathophysiologic knowledge on type 2 diabetes has moved and the disease is nowadays more complex with a loss of the beta cell mass and an insulin resistance state of the liver, muscle and adipocyte tissue associated with a defect in gastro-intestinal hormones in the postprandial state."	2.41	Oral anti diabetic polychemotherapy in type 2 diabetes mellitus. ( Gin, H; Rigalleau, V, 2002)
"Type 2 diabetes is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action."	2.41	Combination oral agent and insulin therapy for type 2 diabetes mellitus. ( Passaro, MD; Ratner, RE, 2001)
"Troglitazone was designed to combine tocopherol, anti-peroxidant, and thiazolidinedione."	2.41	[The development of thiazolidinedione drugs as anti-diabetic agents]. ( Kuzuya, T, 2000)
"Type 2 diabetes is a chronic metabolic derangement that results from defects in both insulin action and secretion."	2.41	New approaches in the treatment of type 2 diabetes. ( Moller, DE; Zhang, BB, 2000)
"Insulin resistance is the major defect in type 2 diabetes."	2.41	[Glitazones (thiazolidinedione)]. ( Ducobu, J; Sternon, J, 2000)
"Insulin resistance is a change in physiologic regulation such that a fixed dose of insulin causes less of an effect on glucose metabolism than occurs in normal individuals."	2.41	Insulin resistance and its treatment by thiazolidinediones. ( Banerji, MA; Lebovitz, HE, 2001)
"Type 2 diabetes is a disorder that has numerous components, including insulin resistance, an insulin secretory defect, and an increase in hepatic glucose production."	2.41	Using thiazolidinediones: rosiglitazone and pioglitazone in clinical practice. ( Peters, AL, 2001)
"Medications used to treat type 2 diabetes are designed to correct one or more of these metabolic abnormalities."	2.41	Oral agents in the management of type 2 diabetes mellitus. ( Feinglos, MN; Luna, B, 2001)
"Insulin resistance is associated with many common diseases including diabetes mellitus, hyperlipidemia and hypertension, and plays an important role for determining their clinical courses."	2.41	[Insulin resistance and cytokine, cytokine receptor]. ( Hamaguchi, T; Hanafusa, T; Matsuzawa, Y; Nakajima, H, 2000)
"Type 2 diabetes is understood to result most often from insulin resistance and insulin deficiency."	2.41	Type 2 diabetes. How new insights, new drugs are changing clinical practice. ( Drexler, AJ; Robertson, C, 2001)
"Troglitazone was the first drug which reached the market."	2.41	[Thiazolidinediones--a new class of oral antidiabetic drugs]. ( Csermely, P; Jermendy, G, 2001)
"Type 2 diabetes is characterized by decreased secretion of insulin and insulin resistance."	2.41	[Insulin sensitizer drugs, thiazolidinediones: current state and prospect]. ( Kuzuya, T, 2001)
"Hyperglycemia in patients with type 2 diabetes mellitus is caused by peripheral insulin resistance, which results in decreased insulin-mediated glucose disposal and increased endogenous glucose production, and inadequate insulin secretion."	2.41	[Clinical difference between thiazolidinediones and biguanides]. ( Hotta, N, 2001)
" In 80% of patients, addition of TZD caused not only the decrease in insulin dosage and/or HbA1c but also the decrease in hypoglycemic events presumably through improvement in insulin profile, i."	2.41	[Clinical usefulness of combination treatment with thiazolidinedione and insulin]. ( Kitamura, R; Tanaka, Y, 2001)
"particularly type 2 diabetes mellitus, and is associated with a higher risk of atherosclerosis and cardiovascular complications."	2.41	Hepatotoxicity with thiazolidinediones: is it a class effect? ( Scheen, AJ, 2001)
"Type 2 diabetes is associated with multiple metabolic abnormalities including insulin resistance and the procoagulant state."	2.41	Mechanism of action of thiazolidinediones. ( Flemmer, M; Scott, J, 2001)
"Obesity is frequently associated with excess caloric fat dietary intake, especially in the form of fatty acids."	2.41	Pharmacological treatment of insulin resistance in obesity. ( Camejo, G; Ljung, B; Oakes, N, 2001)
"Type 2 diabetes is responsible for various micro and macro-vascular complications, appearing early in the course of the disease."	2.41	[Is a new therapeutic class justified in the treatment of type 2 diabetes?]. ( Halimi, S, 2002)
"Type 2 diabetes mellitus is characterized by insulin deficiency but in particular by insulin resistance."	2.41	[Current and future aspects of oral antidiabetic agents in type 2 diabetes]. ( Rybka, J, 2001)
"Insulin resistance is one of the cardinal pathophysiological components of the metabolic syndrome, type 2 diabetes, and frequently co-exists with essential hypertension."	2.40	Insulin resistance: site of the primary defect or how the current and the emerging therapies work. ( Caro, JF; Kolaczynski, JW, 1998)
"Oral therapy for early type 2 diabetes can be relatively inexpensive, and evidence of its cost-effectiveness is accumulating."	2.40	Oral pharmacologic management of type 2 diabetes. ( Riddle, MC, 1999)
"Multicentre, randomized, clinical trials that included over 100 participants comparing antidiabetic agents with a placebo or a different antidiabetic agent and reporting major adverse cardiovascular events (MACEs), or primarily reporting heart failure, were searched in the PubMed, Embase and Cochrane databases."	1.91	Cardiovascular efficacy and safety of antidiabetic agents: A network meta-analysis of randomized controlled trials. ( Frias, JP; Lim, S; Sohn, M, 2023)
"We found no increased risk of acute pancreatitis comparing 49,374 DPP-4I initiators to 132,223 sulfonylurea initiators (weighted HR 1."	1.48	The Risk of Acute Pancreatitis After Initiation of Dipeptidyl Peptidase 4 Inhibitors: Testing a Hypothesis of Subgroup Differences in Older U.S. Adults. ( Buse, JB; Hong, JL; Jonsson Funk, M; Pate, V; Stürmer, T, 2018)
"Type 2 diabetes is increasingly common in HIV-infected individuals."	1.46	Comparative Effectiveness of Diabetic Oral Medications Among HIV-Infected and HIV-Uninfected Veterans. ( Bisson, GP; Gibert, CL; Gordon, K; Han, JH; Leaf, DA; Rimland, D; Rodriguez-Barradas, MC; Womack, JA, 2017)
"In treatment algorithms of type 2 diabetes mellitus in Western countries, biguanides are recommended as first-line agents."	1.46	Prescription of oral hypoglycemic agents for patients with type 2 diabetes mellitus: A retrospective cohort study using a Japanese hospital database. ( Motonaga, R; Nomiyama, T; Tanabe, M; Terawaki, Y; Yanase, T, 2017)
"To describe common type 2 diabetes treatment intensification regimens, patients' characteristics and changes in glycated hemoglobin (HbA1c) and body mass index (BMI)."	1.43	Diabetes treatment intensification and associated changes in HbA1c and body mass index: a cohort study. ( Greevy, RA; Griffin, MR; Grijalva, CG; Hung, AM; Liu, X; Roumie, CL, 2016)
"However, different treatments for type 2 diabetes can affect fracture risk differently, with metaanalyses showing some agents increase risk (eg, thiazolidinediones) and some reduce risk (eg, sitagliptin)."	1.43	Does Sitagliptin Affect the Rate of Osteoporotic Fractures in Type 2 Diabetes? Population-Based Cohort Study. ( Eurich, DT; Josse, RG; Lin, M; Majumdar, SR, 2016)
"Hyperglycemia is associated with increased risk of all-site cancer that may be mediated through activation of the renin-angiotensin-system (RAS) and 3-hydroxy-3-methyl-glutaryl-coenzyme-A-reductase (HMGCR) pathways."	1.40	Additive effects of blood glucose lowering drugs, statins and renin-angiotensin system blockers on all-site cancer risk in patients with type 2 diabetes. ( Chan, JC; Cheung, KK; Chow, CC; Kong, AP; Lee, HM; Luk, A; Ma, RC; Ozaki, R; So, WY; Xu, G; Yang, X; Yu, L, 2014)
"Older individuals with type 2 diabetes are more likely to have moderate cognitive deficits and structural changes in brain tissue."	1.36	Relationships between daily acute glucose fluctuations and cognitive performance among aged type 2 diabetic patients. ( Barbieri, M; Boccardi, V; Canonico, S; Lettieri, B; Marfella, R; Paolisso, G; Rizzo, MR; Vestini, F, 2010)
"Patients with type 2 diabetes who added a sulphonylurea or a thiazolidinedione to ongoing metformin therapy on a date (index date) from January 2001 through January 2006 and who had at least one haemoglobin A1C (HbA1C) measurement in the 12-month period before the visit date were eligible."	1.35	Hypoglycaemic symptoms, treatment satisfaction, adherence and their associations with glycaemic goal in patients with type 2 diabetes mellitus: findings from the Real-Life Effectiveness and Care Patterns of Diabetes Management (RECAP-DM) Study. ( Alvarez Guisasola, F; Krishnarajah, G; Lyu, R; Mavros, P; Tofé Povedano, S; Yin, D, 2008)
"Type 2 diabetes mellitus is a chronic disease with potentially devastating long-term complications."	1.33	Oral agents in managing diabetes mellitus in children and adolescents. ( Jacobson-Dickman, E; Levitsky, L, 2005)
"The patients were those with type 2 diabetes mellitus hospitalized with a first MI and the controls were those with diabetes mellitus randomly selected from the same geographic area."	1.33	Insulin sensitizing pharmacotherapy for prevention of myocardial infarction in patients with diabetes mellitus. ( Berlin, JA; Cappola, AR; Kimmel, SE; Sauer, WH, 2006)
"A 50-year-old obese white man with type 2 diabetes presented with cardiogenic shock."	1.32	Thiazolidinedione-induced congestive heart failure. ( Cheng, AY; Fantus, IG, 2004)
"Outcomes in patients with type 2 diabetes may vary depending on the antidiabetic medication used."	1.32	Healthcare costs and prescription adherence with introduction of thiazolidinedione therapy in Medicaid type 2 diabetic patients: a retrospective data analysis. ( Anderson, RT; Balkrishnan, R; Camacho, FT; Rajagopalan, R; Shenolikar, RA; Whitmire, JT, 2004)
"Diabetes mellitus is a chronic disease that leads to complications including heart disease, stroke, kidney failure, blindness and nerve damage."	1.31	The hormone resistin links obesity to diabetes. ( Ahima, RS; Bailey, ST; Banerjee, RR; Bhat, S; Brown, EJ; Lazar, MA; Patel, HR; Steppan, CM; Wright, CM, 2001)
"Two hundred ninety-one patients with type 2 diabetes mellitus."	1.31	Factors associated with the risk of liver enzyme elevation in patients with type 2 diabetes treated with a thiazolidinedione. ( Khan, MA; Lockheart, MS; Neafus, KL; St Peter, JV; Vessey, JT, 2001)
"Insulin resistance is a characteristic feature of type 2 diabetes and obesity."	1.31	Lipid lowering explains the insulin sensitivity enhancing effects of a thiazolidinedione, 5-(4-(2-(2-phenyl-4-oxazolyl)ethoxy)benzyl)-2,4 thiazolidinedione. ( Johnson, WT; Stephens, TW; Yakubu-Madus, FE, 2000)
"Rosiglitazone was associated with a significant increase in low-density lipoprotein cholesterol (LDL-C) levels (35%, p < 0."	1.31	Differences in lipid profiles of patients given rosiglitazone followed by pioglitazone. ( LaCivita, KA; Villarreal, G, 2002)

Research

Studies (265)

Authors

Clinical Trials (23)

Trial Overview

Trial Outcomes

Death From Any Cause in the Glycemia Trial.

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	9 (3.40)	18.2507
2000's	169 (63.77)	29.6817
2010's	66 (24.91)	24.3611
2020's	21 (7.92)	2.80

Authors	Studies
Abushamat, LA	1
Reusch, JEB	1
Tang, X	2
Brinton, RD	1
Chen, Z	1
Farland, LV	1
Klimentidis, Y	1
Migrino, R	1
Reaven, P	1
Rodgers, K	1
Zhou, JJ	1
Sheu, ML	1
Pan, LY	1
Hu, HY	1
Su, HL	1
Sheehan, J	1
Tsou, HK	1
Pan, HC	1
Wu, H	1
Lau, ESH	1
Yang, A	1
Fan, B	1
Ma, RCW	1
Kong, APS	1
Chow, E	1
So, WY	2
Chan, JCN	1
Luk, AOY	1
Zhao, H	2
Zhuo, L	2
Sun, Y	2
Shen, P	2
Lin, H	2
Zhan, S	2
Kodama, S	1
Fujihara, K	1
Ishiguro, H	1
Matsubayashi, Y	1
Kitazawa, M	1
Iwanaga, M	1
Yamada, T	1
Kato, K	1
Nakagawa, Y	1
Tanaka, S	1
Shimano, H	1
Sone, H	1
Mahmoud, F	1
Mullen, A	1
Sainsbury, C	1
Rushworth, GF	1
Yasin, H	1
Abutheraa, N	1
Mueller, T	1
Kurdi, A	1
Yoo, J	1
Jeon, J	1
Baik, M	1
Kim, J	2
Wasif, U	1
Al-Shehab, U	1
Lo, DF	1
Susilawati, E	1
Levita, J	1
Susilawati, Y	1
Sumiwi, SA	1
Sohn, M	1
Frias, JP	1
Lim, S	1
Shahrear, S	1
Islam, ABMMK	1
de-Lima-Júnior, JC	1
Rodovalho, S	1
Van de Sande-Lee, S	1
Monfort-Pires, M	1
Rachid, B	1
Cintra, RM	1
Ramos, CD	1
Cendes, F	1
Folli, F	1
Velloso, LA	1
Zhang, Z	1
Cao, Y	1
Tao, Y	1
E, M	1
Tang, J	1
Liu, Y	1
Li, F	1
Elsisi, GH	1
Anwar, MM	1
Khattab, M	1
Elebrashy, I	1
Wafa, A	1
Elhadad, H	1
Awad, M	1
Carapinha, JL	1
Zhou, JB	1
Han, M	1
Yang, J	1
Simó, R	2
Shannon, CE	1
Ragavan, M	1
Palavicini, JP	1
Fourcaudot, M	1
Bakewell, TM	1
Valdez, IA	1
Ayala, I	1
Jin, ES	1
Madesh, M	1
Han, X	2
Merritt, ME	1
Norton, L	1
Veelen, A	1
Erazo-Tapia, E	1
Oscarsson, J	1
Schrauwen, P	1
Yang, BR	1
Cha, SH	1
Lee, KE	1
Kim, JW	1
Lee, J	1
Shin, KH	1
Ha, KH	2
Kim, B	1
Choi, H	1
Kim, DJ	2
Kim, HC	2
Vora, J	1
Ray, K	1
Kosiborod, M	2
Poulter, NR	1
Rajagopalan, S	1
Leiter, LA	3
Devi, RN	1
Khrenova, MG	1
Israel, S	1
Anzline, C	1
Astakhov, AA	1
Tsirelson, VG	1
Chu, WM	1
Ho, HE	1
Huang, KH	1
Tsan, YT	1
Liou, YS	1
Wang, YH	1
Lee, MC	1
Li, YC	1
Yasmin, S	1
Capone, F	1
Laghezza, A	1
Piaz, FD	1
Loiodice, F	1
Vijayan, V	1
Devadasan, V	1
Mondal, SK	1
Atlı, Ö	1
Baysal, M	1
Pattnaik, AK	1
Jayaprakash, V	1
Lavecchia, A	1
Heintjes, EM	1
Overbeek, JA	1
Hall, GC	2
Prieto-Alhambra, D	1
Lapi, F	1
Hammar, N	1
Bezemer, ID	1
Nanjan, MJ	1
Mohammed, M	1
Prashantha Kumar, BR	1
Chandrasekar, MJN	1
Yoon, JH	1
Min, SH	1
Ahn, CH	1
Cho, YM	1
Hahn, S	1
Hong, JL	1
Buse, JB	2
Jonsson Funk, M	1
Pate, V	1
Stürmer, T	2
van Baar, MJB	1
van Ruiten, CC	1
Muskiet, MHA	1
van Bloemendaal, L	1
IJzerman, RG	1
van Raalte, DH	1
Powell, WR	1
Christiansen, CL	1
Miller, DR	1
Lee, SJ	1
Lee, JH	1
Lee, H	1
Verma, SK	1
Yadav, YS	1
Thareja, S	1
Dennis, JM	1
Shields, BM	1
Henley, WE	1
Jones, AG	1
Hattersley, AT	2
Huiying, Z	1
Guangying, C	1
Shiyang, Z	1
Arnold, SV	1
Inzucchi, SE	2
Echouffo-Tcheugui, JB	1
Tang, F	1
Lam, CSP	1
Sperling, LS	1
Lee, SA	1
Kim, YR	1
Yang, EJ	1
Kwon, EJ	1
Kim, SH	1
Kang, SH	1
Park, DB	1
Oh, BC	1
Heo, ST	1
Koh, G	1
Lee, DH	1
Karyekar, CS	1
Ravichandran, S	2
Allen, E	3
Fleming, D	2
Frederich, R	2
Koffarnus, RL	1
Wargo, KA	1
Phillippe, HM	1
Cook, W	1
Bryzinski, B	1
Slater, J	1
Curkendall, SM	1
Thomas, N	1
Bell, KF	1
Juneau, PL	1
Weiss, AJ	1
Curry, A	1
Linz, PE	1
Lovato, LC	1
Byington, RP	1
O'Connor, PJ	1
Weiss, D	1
Force, RW	1
Crouse, JR	1
Ismail-Beigi, F	1
Simmons, DL	1
Papademetriou, V	1
Ginsberg, HN	1
Elam, MB	1
Dziuba, J	1
Alperin, P	1
Racketa, J	1
Iloeje, U	1
Goswami, D	1
Hardy, E	1
Perlstein, I	1
Grossman, HL	1
Cohen, M	1
Umetsu, R	1
Nishibata, Y	1
Abe, J	1
Suzuki, Y	1
Hara, H	1
Nagasawa, H	1
Kinosada, Y	1
Nakamura, M	1
Hampp, C	1
Borders-Hemphill, V	1
Moeny, DG	1
Wysowski, DK	1
Dai, X	1
Wang, H	1
Jing, Z	1
Fu, P	1
Kong, AP	1
Yang, X	1
Luk, A	1
Ma, RC	1
Ozaki, R	1
Cheung, KK	1
Lee, HM	1
Yu, L	1
Xu, G	1
Chow, CC	1
Chan, JC	1
Araki, E	1
Tanizawa, Y	2
Tanaka, Y	2
Taniguchi, A	1
Koiwai, K	1
Kim, G	1
Salsali, A	1
Woerle, HJ	1
Broedl, UC	1
Schernthaner, G	1
Rosas-Guzmán, J	1
Dotta, F	2
Guerci, B	1
Festa, A	1
Kiljański, J	1
Zhou, M	1
Gallwitz, B	1
Chen, R	2
Yan, J	1
Liu, P	1
Wang, Z	2
Kannan, S	1
Pantalone, KM	1
Matsuda, S	1
Wells, BJ	1
Karafa, M	1
Zimmerman, RS	1
Flowers, E	1
Aouizerat, BE	1
Abbasi, F	1
Lamendola, C	1
Grove, KM	1
Fukuoka, Y	1
Reaven, GM	1
Chen, HH	1
Horng, MH	1
Yeh, SY	1
Lin, IC	1
Yeh, CJ	1
Muo, CH	1
Sung, FC	1
Kao, CH	1
Connolly, JG	1
Bykov, K	1
Gagne, JJ	1
Farmer, AJ	1
Rodgers, LR	1
Lonergan, M	1
Shields, B	1
Weedon, MN	1
Donnelly, L	1
Holman, RR	1
Pearson, ER	1
Majumdar, SR	1
Josse, RG	1
Lin, M	1
Eurich, DT	1
Roumie, CL	1
Greevy, RA	1
Grijalva, CG	1
Hung, AM	1
Liu, X	2
Griffin, MR	1
Cai, X	1
Yang, W	1
Chen, Y	1
Gao, X	1
Zhou, L	1
Zhang, S	1
Ji, L	1
Tanabe, M	1
Motonaga, R	1
Terawaki, Y	1
Nomiyama, T	1
Yanase, T	2
Han, JH	1
Gordon, K	1
Womack, JA	1
Gibert, CL	1
Leaf, DA	1
Rimland, D	1
Rodriguez-Barradas, MC	1
Bisson, GP	1
Ojo, O	1
Lin, KD	1
Chang, YH	1
Wang, CL	1
Yang, YH	1
Hsiao, PJ	1
Li, TH	1
Shin, SJ	1
Ma, J	1
Liu, W	1
Hunter, A	1
Zhang, W	1
Koro, CE	1
Fu, Q	1
Stender, M	1
Ribowsky, J	1
Covino, J	1
Lewis, JD	1
Capra, AM	1
Achacoso, NS	1
Ferrara, A	1
Levin, TR	1
Quesenberry, CP	1
Habel, LA	1
Jermendy, G	2
Erdesz, D	1
Nagy, L	1
Yin, D	3
Phatak, H	1
Karve, S	1
Engel, S	1
Balkrishnan, R	3
Michaelson, J	1
Toulis, KA	1
Goulis, DG	1
Anastasilakis, AD	1
Reblin, T	1
Barnett, AH	2
Frye, RL	2
August, P	1
Brooks, MM	2
Hardison, RM	2
Kelsey, SF	1
MacGregor, JM	1
Orchard, TJ	1
Chaitman, BR	1
Genuth, SM	1
Goldberg, SH	1
Hlatky, MA	1
Jones, TL	1
Molitch, ME	1
Nesto, RW	1
Sako, EY	1
Sobel, BE	2
Rattinger, G	1
Bero, L	1
Gastaldelli, A	1
Harrison, SA	1
Belfort-Aguilar, R	1
Hardies, LJ	1
Balas, B	1
Schenker, S	1
Cusi, K	1
Mathieu, C	1
Cuddihy, R	1
Arakaki, RF	1
Belin, RM	1
Planquois, JM	1
Lyons, JN	1
Heilmann, CR	1
Simpson, F	1
Whitehead, JP	1
Krumholz, HM	1
Ambrosius, WT	1
Danis, RP	1
Goff, DC	1
Greven, CM	1
Gerstein, HC	2
Cohen, RM	1
Riddle, MC	2
Miller, ME	1
Bonds, DE	1
Peterson, KA	1
Rosenberg, YD	1
Perdue, LH	1
Esser, BA	1
Seaquist, LA	1
Felicetta, JV	1
Chew, EY	1
Störk, S	1
Ertl, G	1
Nitschmann, S	1
Thayer, S	1
Arondekar, B	1
Harley, C	1
Darkow, TE	1
Eto, K	1
Tumenbayar, B	1
Nagashima, S	1
Tazoe, F	1
Miyamoto, M	1
Takahashi, M	1
Ando, A	1
Okada, K	1
Yagyu, H	1
Ishibashi, S	1
Rizzo, MR	1
Marfella, R	1
Barbieri, M	1
Boccardi, V	1
Vestini, F	1
Lettieri, B	1
Canonico, S	1
Paolisso, G	1
Riche, DM	1
King, ST	1
Bailey, SD	1
Xie, C	1
Do, R	1
Montpetit, A	1
Diaz, R	1
Mohan, V	1
Keavney, B	1
Yusuf, S	1
Engert, JC	1
Anand, S	1
Banerji, MA	2
Purkayastha, D	1
Francis, BH	1
Lund, JL	1
Porter, CQ	1
Sandler, RS	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
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
Efficacy, Safety & Tolerability of Combination of Ertugliflozin and Sitagliptin in Patients With Type II Diabetes Mellitus[NCT05556291]		190 participants (Anticipated)	Observational	2022-12-01	Recruiting
Efficacy of Glucagon-like Peptide-1 Receptor Agonists According to Type 2 Diabetes Subtypes: an Italian Monocentric Retrospective Study[NCT06120556]		128 participants (Anticipated)	Observational	2023-06-10	Recruiting
"Peripheral Blood Dipeptidylpeptidase IV (CD26) Positive Leukemic Stem Cells in Chronic Myeloid Leukemia as a Diagnostic Marker"[NCT05543161]		50 participants (Anticipated)	Observational	2022-10-31	Not yet recruiting
Action to Control Cardiovascular Risk in Diabetes (ACCORD)[NCT00000620]	Phase 3	10,251 participants (Actual)	Interventional	1999-09-30	Completed
A 52-week, Randomised, Multi-centre, Parallel Group Study to Investigate the Safety and Efficacy of BI 10773 (10 mg or 25 mg Administered Orally Once Daily) as add-on Therapy to an Oral Antidiabetic Drug (Sulfonylurea, Biguanide, Thiazolidinedione, Alpha [NCT01368081]	Phase 3	1,162 participants (Actual)	Interventional	2011-05-31	Completed
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
Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes[NCT00006305]	Phase 3	2,368 participants (Actual)	Interventional	2000-09-30	Completed
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
Effect of Modifying Anti-platelet Treatment to Ticagrelor in Patients With Diabetes and Low Response to Clopidogrel[NCT01643031]	Phase 4	500 participants (Anticipated)	Interventional	2012-08-31	Not yet recruiting
Role of Pioglitazone in the Treatment of Non-alcoholic Steatohepatitis (NASH)[NCT00227110]	Phase 4	55 participants (Actual)	Interventional	2002-10-31	Completed
Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study[NCT00542178]	Phase 3	3,472 participants (Actual)	Interventional	2003-10-31	Completed
"A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial to Evaluate the Efficacy and Safety of BMS-477118 in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone"[NCT00121667]	Phase 3	1,462 participants (Actual)	Interventional	2005-08-31	Completed
A Multicenter, Randomized, Double Blind, Placebo Controlled, Phase III Trial to Evaluate the Efficacy and Safety of Saxagliptin (BMS477118) in Combination With Thiazolidinedione Therapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control[NCT00295633]	Phase 3	565 participants (Actual)	Interventional	2006-03-31	Completed
A Multicenter, Randomized, Double-Blind Placebo-Controlled Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin in Combination With Glyburide in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Glyburide Alone[NCT00313313]	Phase 3	768 participants (Actual)	Interventional	2006-04-30	Completed
A Randomized, Double-Blind, Parallel, Multicenter Study to Evaluate the Efficacy and Safety of Simvastatin Monotherapy Compared With Simvastatin Plus Ezetimibe (SCH 58235) in Type 2 Diabetic Patients Treated With Thiazolidinediones[NCT00551876]	Phase 3	214 participants (Actual)	Interventional	2001-12-31	Completed
Rosiglitazone-Induced Weight Gain[NCT00225225]		45 participants (Actual)	Interventional	2002-10-31	Terminated (stopped due to due to published data on Rosiglitazone)
Efficacy and Safety of Vildagliptin in Combination With Pioglitazone in Patients With Type 2 Diabetes[NCT00099853]	Phase 3	362 participants (Actual)	Interventional	2004-05-31	Completed
Safety and Efficacy of Exenatide in Patients With Type 2 Diabetes Using Thiazolidinediones or Thiazolidinediones and Metformin[NCT00099320]	Phase 3	182 participants (Actual)	Interventional	2004-05-31	Completed
Vildagliptin Compared to Pioglitazone in Combination With Metformin in Patients With Type 2 Diabetes[NCT00237237]	Phase 3	588 participants	Interventional	2005-10-31	Completed
Relationship Between Obesity and Periodontal Disease[NCT02508415]		62 participants (Actual)	Interventional	2013-02-28	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 Rehabilitation Programme in Adapted Physical Activity (APA) Among Type 2 Diabetics Persons[NCT00234273]	Phase 2	10 participants (Actual)	Interventional	2004-11-30	Terminated (stopped due to recrutment)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

"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.

Intervention	participants (Number)
Glycemia Trial: Intensive Control	391
Glycemia Trial: Standard Control	327

"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.

Intervention	participants (Number)
Glycemia Trial: Intensive Control	503
Glycemia Trial: Standard Control	543

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.

Intervention	participants (Number)
BP Trial: Intensive Control	208
BP Trial: Standard Control	237

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.

Intervention	participants (Number)
Lipid Trial: Fenofibrate	291
Lipid Trial: Placebo	310

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.

Intervention	participants (Number)
Lipid Trial: Fenofibrate	641
Lipid Trial: Placebo	667

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

Change From Baseline in HbA1c

Intervention	participants (Number)
BP Trial: Intensive Control	36
BP Trial: Standard Control	62

Change from baseline in HbA1c after 52 weeks of treatment (NCT01368081)
Timeframe: Baseline and 52 weeks

Confirmed Hypoglycaemic Adverse Events

Intervention	percentage of HbA1c (Least Squares Mean)
Sulfonylurea: Empa 10mg	-0.93
Sulfonylurea: Empa 25mg	-0.96
Sulfonylurea: Metformin	-0.97
Biguanide: Empa 10mg	-0.81
Biguanide: Empa 25mg	-0.98
Thiazolidinedione: Empa 10mg	-0.90
Thiazolidinedione: Empa 25mg	-0.96
Alpha Glucosidase Inhibitor: Empa 10mg	-0.87
Alpha Glucosidase Inhibitor: Empa 25mg	-0.77
DPP-IV Inhibitor: Empa 10mg	-1.00
DPP-IV Inhibitor: Empa 25mg	-0.83
Glinide: Empa 10mg	-0.98
Glinide: Empa 25mg	-0.98

Number of patients with confirmed hypoglycaemic adverse events (NCT01368081)
Timeframe: After the first drug intake until 7 days after the last treatment administration, up to 383 days

Number of Patients With Drug Related Adverse Events

Intervention	participants (Number)
Sulfonylurea: Empa 10mg	6
Sulfonylurea: Empa 25mg	9
Sulfonylurea: Metformin	5
Biguanide: Empa 10mg	0
Biguanide: Empa 25mg	1
Thiazolidinedione: Empa 10mg	2
Thiazolidinedione: Empa 25mg	1
Alpha Glucosidase Inhibitor: Empa 10mg	0
Alpha Glucosidase Inhibitor: Empa 25mg	0
DPP-IV Inhibitor: Empa 10mg	0
DPP-IV Inhibitor: Empa 25mg	1
Glinide: Empa 10mg	0
Glinide: Empa 25mg	2

Number of Patients With Drug Related Adverse Events after the first drug intake until 7 days after the last treatment administration, up to 383 days (NCT01368081)
Timeframe: After the first drug intake until 7 days after the last treatment administration, up to 383 days

Change in Body Weight From Baseline to Year 3

Intervention	participants (Number)
Sulfonylurea: Empa 10mg	19
Sulfonylurea: Empa 25mg	25
Sulfonylurea: Metformin	13
Biguanide: Empa 10mg	13
Biguanide: Empa 25mg	9
Thiazolidinedione: Empa 10mg	20
Thiazolidinedione: Empa 25mg	19
Alpha Glucosidase Inhibitor: Empa 10mg	7
Alpha Glucosidase Inhibitor: Empa 25mg	5
DPP-IV Inhibitor: Empa 10mg	9
DPP-IV Inhibitor: Empa 25mg	18
Glinide: Empa 10mg	9
Glinide: Empa 25mg	9

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

Intervention	kg (Least Squares Mean)
Exen + Met	-3.92
Glim + Met	1.47

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

Intervention	ratio (Least Squares Mean)
Exen + Met	12.10
Glim + Met	0.91

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

Intervention	ratio (Least Squares Mean)
Exen + Met	9.15
Glim + Met	1.82

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.

Intervention	mmol/L (Least Squares Mean)
Exen + Met	-0.87
Glim + Met	-0.41

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

Intervention	ratio (Least Squares Mean)
Exen + Met	0.03
Glim + Met	0.05

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

Intervention	percentage of total hemoglobin (Least Squares Mean)
Exen + Met	-0.36
Glim + Met	-0.21

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

Intervention	percentage of total hemoglobin (Mean)
Glim + Met + Exen - Not Randomized	-0.47

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

Intervention	percentage of total hemoglobin (Least Squares Mean)
Exen + Met + Glim - Randomized	-0.19
Exen + Met + Pio or Rosi - Randomized	-0.47

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

Change in HOMA-B From Baseline to Endpoint

Intervention	percentage of total hemoglobin (Least Squares Mean)
Exen + Met	-0.30
Glim + Met	-0.12

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

Intervention	ratio (Least Squares Mean)
Exen + Met	5.56
Glim + Met	19.92

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

Intervention	mmol/L (Least Squares Mean)
Exen + Met	-2.72
Glim + Met	-0.53

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

Disposition Index at Year 3

Intervention	mmHg (Least Squares Mean)
Exen + Met	77.45
Glim + Met	79.16

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

Intervention	ratio (Least Squares Mean)
Exen + Met	12.56
Glim + Met	7.89

Intervention	mmol/L (Least Squares Mean)
Exen + Met	7.27
Glim + Met	7.96

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

Intervention	ratio (Least Squares Mean)
Exen + Met	0.22
Glim + Met	0.23

Intervention	beats per minute (Least Squares Mean)
Exen + Met	73.51
Glim + Met	74.23

Intervention	mmol/L (Least Squares Mean)
Exen + Met	1.31
Glim + Met	1.25

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

Intervention	ratio (Least Squares Mean)
Exen + Met	66.86
Glim + Met	68.52

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

Intervention	events per subject-year (Least Squares Mean)
Exen + Met	1.52
Glim + Met	5.32

Postprandial (2 Hours) Plasma Glucose at Year 3

Intervention	events per subject-year (Mean)
Exen + Metformin + Glim - Randomized	2.78
Exen + Met + Pio or Rosi - Randomized	0.60
Glim + Met + Exen - Not Randomized	4.62

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

Intervention	mmol/L (Least Squares Mean)
Exen + Met	12.65
Glim + Met	15.45

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

Intervention	ratio (Least Squares Mean)
Exen + Met	25.81
Glim + Met	26.38

Intervention	mmHg (Least Squares Mean)
Exen + Met	130.58
Glim + Met	135.78

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

Intervention	week (Median)
Exen + Met	180.0
Glim + Met	142.1

Intervention	mmol/L (Least Squares Mean)
Exen + Met	4.77
Glim + Met	4.75

Intervention	mmol/L (Least Squares Mean)
Exen + Met	1.69
Glim + Met	1.95

Number of Participants With All-Cause Mortality

Number of Participants With Death, Myocardial Infarction, or Stroke

Cataract Extraction

Development or Progression of Macular Edema

Loss of Visual Acuity

Number of Participants With Progression of Diabetic Retinopathy of at Least 3 Stages on the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale, or Development of Proliferative Diabetic Retinopathy Necessitating Photocoagulation Therapy or Vitrectomy

Intervention	number of patients (Number)
	Number of patients with treatment failure	Number of patients censored
Exen + Met	203	287
Glim + Met	262	225

Intervention	participants (Number)
Revascularization and Insulin Providing (IP)	80
Revascularization and Insulin Sensitizing (IS)	75
Medical Therapy and Insulin Providing (IP)	80
Medical Therapy and Insulin Sensitizing (IS)	81

Intervention	participants (Number)
Revascularization and Insulin Providing (IP)	145
Revascularization and Insulin Sensitizing (IS)	121
Medical Therapy and Insulin Providing (IP)	143
Medical Therapy and Insulin Sensitizing (IS)	140

Intervention	Participants (Count of Participants)
Intensive Glycemia Control	547
Standard Glycemia Control	623
Intensive Blood Pressure Control	266
Standard Blood Pressure Control	300
Fenofibrate + Simvastatin Therapy	305
Placebo + Simvastatin Therapy	299

Intervention	Participants (Count of Participants)
Intensive Glycemia Control	44
Standard Glycemia Control	40
Intensive Blood Pressure Control	18
Standard Blood Pressure Control	20
Fenofibrate + Simvastatin Therapy	24
Placebo + Simvastatin Therapy	22

Intervention	Participants (Count of Participants)
Intensive Glycemia Control	744
Standard Glycemia Control	752
Intensive Blood Pressure Control	367
Standard Blood Pressure Control	382
Fenofibrate + Simvastatin Therapy	354
Placebo + Simvastatin Therapy	393

Diabetic retinopathy status was defined according to the eye with the highest level on the ETDRS Final Severity Scale for Persons, as follows: no diabetic retinopathy, a level of less than 20; mild diabetic retinopathy, a level of 20; moderate nonproliferative diabetic retinopathy (NPDR), a level above 20 but less than 53; severe diabetic retinopathy, a level of 53 but less than 60; and proliferative diabetic retinopathy (PDR), a level of 60 or higher. (NCT00542178)
Timeframe: Measured at Year 4

All Reported Hypoglycemic Adverse Events During the ST + LT Treatment Period

Intervention	participants (Number)
Intensive Glycemia Control	104
Standard Glycemia Control	149
Intensive Blood Pressure Control	67
Standard Blood Pressure Control	54
Fenofibrate + Simvastatin Therapy	52
Placebo + Simvastatin Therapy	80

Hypoglycemic Events are based upon the Saxagliptin Predefined List of Events, which are hypoglycemia, blood glucose decreased, and hypoglycemic unconsciousness. (NCT00121667)
Timeframe: AEs: up to last treatment day + 1 day or last visit day in the ST+LT period; SAEs: up to last treatment day + 30 days or last visit day + 30 days in the LT+ST period. Mean duration of exposure: 124, 118, 130, 95 wks respectively for 2.5mg, 5mg, 10 mg, pla

Confirmed Hypoglycemia During the ST + LT Treatment Period

Intervention	participants (Number)
Saxagliptin 2.5 mg + Metformin	23
Saxagliptin 5 mg + Metformin	20
Saxagliptin 10 mg + Metformin	21
Placebo+ Metformin	20

'Confirmed' = recorded on the hypoglycemia AE case report form with a fingerstick glucose <= 50 mg/dL and associated symptoms. (NCT00121667)
Timeframe: AEs: up to last treatment day + 1 day or last visit day in the ST+LT period; SAEs: up to last treatment day + 30 days or last visit day + 30 days in the LT+ST period. Mean duration of exposure: 124, 118, 130, 95 wks respectively for 2.5mg, 5mg, 10 mg, pla

Percentage of Participants Achieving Therapeutic Glycemic Response (A1C < 7.0%) at Week 24

Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC)

Intervention	participants (Number)
Saxagliptin 2.5 mg + Metformin	3
Saxagliptin 5 mg + Metformin	2
Saxagliptin 10 mg + Metformin	3
Placebo+ Metformin	1

Intervention	percentage of participants (Number)
Saxagliptin 2.5 mg + Metformin	37.1
Saxagliptin 5 mg + Metformin	43.5
Saxagliptin 10 mg + Metformin	44.4
Placebo+ Metformin	16.6

Mean change from baseline is adjusted for baseline value. (NCT00121667)
Timeframe: Baseline, Week 24

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

Intervention	mg*min/dL (Mean)
	Baseline Mean	Adjusted Mean Change from Baseline
Placebo+ Metformin	47407	-3291
Saxagliptin 10 mg + Metformin	44931	-8137
Saxagliptin 2.5 mg + Metformin	48224	-8891
Saxagliptin 5 mg + Metformin	49021	-9586

Mean change from baseline is adjusted for baseline value. (NCT00121667)
Timeframe: Baseline, Week 24

Baseline and Change From Baseline in Hemoglobin A1c (A1C) at Week 24

Mean change from baseline is adjusted for baseline value. (NCT00121667)
Timeframe: Baseline, Week 24

Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period