Page last updated: 2024-10-30

metformin and Nausea

metformin has been researched along with Nausea in 41 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.

Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.

Research Excerpts

ExcerptRelevanceReference
"Treatment with Metformin XR in participants admitted with stroke and with pre-diabetes is feasible and safe."9.41Feasibility trial of metformin XR in people with pre-diabetes and stroke (MIPPS)-randomised open blinded endpoint controlled trial. ( Borschmann, K; Churilov, L; Donnan, G; Ekinci, EI; Hachem, M; Lau, LH; Price, SAL; Sumithran, P; Tabesh, M; Thijs, V; Zajac, J, 2021)
"Exenatide is an analogue of GLP1 designed to improve the glycemic control in patients with obesity and type 2 diabetes."9.16[Metabolic control and weight loss in patients with obesity and type 2 diabetes mellitus, treated with exenatide]. ( Ferrer Gómez, M; García Zafra, MV; Hellín Gil, MD; Pujante Alarcón, P; Román, LM; Tébar Massó, J, 2012)
" Pioglitazone treatment (n = 10) reduced hepatic fat as assessed by magnetic resonance spectroscopy, despite a significant increase in body weight (Δ = 3."9.15Exenatide decreases hepatic fibroblast growth factor 21 resistance in non-alcoholic fatty liver disease in a mouse model of obesity and in a randomised controlled trial. ( Bajaj, M; Chan, L; Gonzalez, EV; Gutierrez, A; Jogi, M; Krishnamurthy, R; Muthupillai, R; Samson, SL; Sathyanarayana, P, 2011)
"BACKGROUND Metformin-associated lactic acidosis (MALA) is a relatively rare adverse effect of metformin therapy."8.12Transient Complete Blindness Due to Metformin-Associated Lactic Acidosis (MALA) Reversed with Hemodialysis. ( Barusya, C; Charokopos, A; Dumic, I; Knopps, L; Rueda Prada, L; Subramanian, A; Zurob, AS, 2022)
"Lactic acidosis is a rare, serious adverse effect of metformin, which can be prevented by carefully observing the contra-indications."6.41[Metformin efficacious in poorly controlled diabetes mellitus type 2]. ( Hoekstra, JB; Holleman, F; Stades, AM, 2000)
"Treatment with Metformin XR in participants admitted with stroke and with pre-diabetes is feasible and safe."5.41Feasibility trial of metformin XR in people with pre-diabetes and stroke (MIPPS)-randomised open blinded endpoint controlled trial. ( Borschmann, K; Churilov, L; Donnan, G; Ekinci, EI; Hachem, M; Lau, LH; Price, SAL; Sumithran, P; Tabesh, M; Thijs, V; Zajac, J, 2021)
"Compared with glimepiride, Sita/Met as an initial treatment led to significantly greater improvements in glycemic control and body weight changes, with a lower incidence of hypoglycemia, over 30 weeks."5.24Efficacy and safety of sitagliptin/metformin fixed-dose combination compared with glimepiride in patients with type 2 diabetes: A multicenter randomized double-blind study. ( Chung, SC; Kim, IJ; Kim, SS; Kim, YI; Lee, KJ; Lee, SJ; Lee, YS; Park, JH, 2017)
" In these studies, metformin use was associated with higher risk of abdominal pain, diarrhea and nausea comparing to control."5.22Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: A systematic review, meta-analysis and meta-regression of randomized controlled trials. ( Gumprecht, J; Hendel, M; Irlik, K; Januszkiewicz, K; Kwiendacz, H; Lip, GYH; Nabrdalik, K; Skonieczna-Żydecka, K; Łoniewski, I, 2022)
"There is low-certainty evidence to suggest that metformin may be effective in preventing weight gain."5.22Pharmacological interventions for prevention of weight gain in people with schizophrenia. ( Agarwal, SM; Ahsan, ZA; Cohn, T; Duncan, MJ; Faulkner, GEJ; Hahn, M; Lockwood, JT; Remington, G; Stogios, N; Takeuchi, H; Taylor, VH, 2022)
"Liraglutide provided better glycaemic control and greater body weight reduction than sitagliptin when administered as add-on to metformin."5.22Efficacy and safety of liraglutide versus sitagliptin, both in combination with metformin, in Chinese patients with type 2 diabetes: a 26-week, open-label, randomized, active comparator clinical trial. ( Bian, F; Bosch-Traberg, H; Geng, J; Li, Y; Liu, J; Liu, Y; Luo, Y; Lv, X; Mu, Y; Peng, Y; Sun, Y; Yang, J; Zang, L, 2016)
"Subjects insufficiently controlled with sitagliptin who switch to liraglutide can obtain clinically relevant reductions in glycaemia and body weight, without compromising safety."5.22Efficacy and safety of switching from sitagliptin to liraglutide in subjects with type 2 diabetes (LIRA-SWITCH): a randomized, double-blind, double-dummy, active-controlled 26-week trial. ( Bailey, TS; Kaltoft, MS; Maislos, M; Rao, PV; Takács, R; Thomsen, AB; Tinahones, FJ; Tsoukas, GM, 2016)
"Metformin administration reduced occurrence of chemotherapy induced-nausea."5.20Metformin Addition to Chemotherapy in Stage IV Non-Small Cell Lung Cancer: an Open Label Randomized Controlled Study. ( Badary, O; El Wakeel, L; Elkholy, E; Saad, AS; Sayed, R, 2015)
"Exenatide is an analogue of GLP1 designed to improve the glycemic control in patients with obesity and type 2 diabetes."5.16[Metabolic control and weight loss in patients with obesity and type 2 diabetes mellitus, treated with exenatide]. ( Ferrer Gómez, M; García Zafra, MV; Hellín Gil, MD; Pujante Alarcón, P; Román, LM; Tébar Massó, J, 2012)
"Exenatide demonstrated more beneficial effects on HbA(1C), weight reduction and insulin resistance during 26 weeks of treatment, but there were more hypoglycemic events and mild-to-moderate nausea compared with metformin."5.16Efficacy and tolerability of exenatide monotherapy in obese patients with newly diagnosed type 2 diabetes: a randomized, 26 weeks metformin-controlled, parallel-group study. ( Gao, Y; Guo, XH; Huang, YY; Song, WL; Yuan, GH, 2012)
" Pioglitazone treatment (n = 10) reduced hepatic fat as assessed by magnetic resonance spectroscopy, despite a significant increase in body weight (Δ = 3."5.15Exenatide decreases hepatic fibroblast growth factor 21 resistance in non-alcoholic fatty liver disease in a mouse model of obesity and in a randomised controlled trial. ( Bajaj, M; Chan, L; Gonzalez, EV; Gutierrez, A; Jogi, M; Krishnamurthy, R; Muthupillai, R; Samson, SL; Sathyanarayana, P, 2011)
" We performed a systematic analysis and compared the proportion of patients reporting nausea, vomiting or diarrhoea, for different doses and glucose-lowering background medications, and relative to a reference compound within the subclasses of short- (exenatide b."4.95Occurrence of nausea, vomiting and diarrhoea reported as adverse events in clinical trials studying glucagon-like peptide-1 receptor agonists: A systematic analysis of published clinical trials. ( Abd El Aziz, MS; Bettge, K; Kahle, M; Meier, JJ; Nauck, MA, 2017)
"7% as monotherapy or in combination with metformin (MET), sulfonylureas (SFU), and/or thiazolidinediones (TZD); with mean weight losses of -1."4.89Evolution of exenatide as a diabetes therapeutic. ( Bhavsar, S; Cherrington, A; Mudaliar, S, 2013)
"BACKGROUND Metformin-associated lactic acidosis (MALA) is a relatively rare adverse effect of metformin therapy."4.12Transient Complete Blindness Due to Metformin-Associated Lactic Acidosis (MALA) Reversed with Hemodialysis. ( Barusya, C; Charokopos, A; Dumic, I; Knopps, L; Rueda Prada, L; Subramanian, A; Zurob, AS, 2022)
" People who received PEX168 alone or with metformin showed more common gastrointestinal adverse effects, especially nausea and vomiting (p < 0."3.01Efficacy and safety of polyethylene glycol loxenatide in type 2 diabetic patients: a systematic review and meta-analysis of randomized controlled trials. ( Abd-Elgawad, M; Abdelhaleem, IA; Abo-Elnour, DE; Abualkhair, KA; Elsayed, E; Hasan, MT; Mahmoud, A; Marey, A; Salamah, HM, 2023)
"In patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks."3.01Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. ( Bergman, BK; Brown, K; Cui, X; Davies, MJ; Fernández Landó, L; Frías, JP; Liu, B; Pérez Manghi, FC; Rosenstock, J, 2021)
"Nondiabetic patients with LAHNSCC were enrolled in the current study to receive escalating doses of metformin and CRT based on the modified toxicity probability interval design."2.94Phase 1 dose-finding study of metformin in combination with concurrent cisplatin and radiotherapy in patients with locally advanced head and neck squamous cell cancer. ( Desai, J; Desai, PB; Gulati, S; Gutkind, JS; Jandarov, R; Mierzwa, M; Molinolo, A; Morris, JC; Palackdharry, SM; Riaz, MK; Sadraei, NH; Takiar, V; Wise-Draper, TM; Zhu, Z, 2020)
" The most frequent adverse reactions in the PEX168 groups were mild to moderate dose-dependent gastrointestinal reactions."2.84Polyethylene glycol loxenatide injections added to metformin effectively improve glycemic control and exhibit favorable safety in type 2 diabetic patients. ( Chen, X; Cheng, Q; Jiang, H; Li, X; Li, Y; Lu, D; Lv, X; Peng, Y; Piao, C; Sun, L; Xiao, X; Xie, Y; Yang, G; Yang, J; Yang, W; Zhang, X; Zheng, S, 2017)
"In Asian patients with type 2 diabetes mellitus insufficiently controlled on metformin ± sulfonylurea, lixisenatide significantly improved glycaemic control and was well tolerated during the 24-week study."2.79Lixisenatide treatment improves glycaemic control in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin with or without sulfonylurea: a randomized, double-blind, placebo-controlled, 24-week trial (GetGoal-M-Asia). ( Feng, P; Han, P; Jin Kui, Y; Liu, X; Lv, X; Niemoeller, E; Shang, S; Su, B; Tian, H; Yan, S; Yu Pan, C; Zhou, Z, 2014)
" Subjects were monitored for adverse events (AEs) throughout the study and 4-week follow-up."2.75Safety and tolerability of high doses of taspoglutide, a once-weekly human GLP-1 analogue, in diabetic patients treated with metformin: a randomized double-blind placebo-controlled study. ( Asnaghi, V; Balena, R; Boldrin, M; Kapitza, C; Nauck, M; Ratner, R, 2010)
"Exenatide added to TZDs alone or in combination with metformin significantly improved glycaemic control as determined by significant improvement in HbA(1c) without associated hypoglycaemia."2.75A placebo-controlled trial of exenatide twice-daily added to thiazolidinediones alone or in combination with metformin. ( Cao, D; Liutkus, J; Northrup, J; Norwood, P; Pop, L; Rosas Guzman, J; Trautmann, M, 2010)
"Metformin XR was well tolerated; gastrointestinal side effects were more common with metformin XR vs."2.71Efficacy, dose-response relationship and safety of once-daily extended-release metformin (Glucophage XR) in type 2 diabetic patients with inadequate glycaemic control despite prior treatment with diet and exercise: results from two double-blind, placebo-c ( Brazg, RL; Bruce, S; Fujioka, K; Joyal, S; Pans, M; Raz, I; Swanink, R, 2005)
" The daily dosage of phenformin and metformin was increased at weekly intervals up to 300 mg."2.63Weight-reducing effect of diguanides in obese non-diabetic women. ( Duncan, LJ; MacCuish, AC; Marshall, A; Munro, JF; Wilson, EM, 1969)
"Lactic acidosis is a rare, serious adverse effect of metformin, which can be prevented by carefully observing the contra-indications."2.41[Metformin efficacious in poorly controlled diabetes mellitus type 2]. ( Hoekstra, JB; Holleman, F; Stades, AM, 2000)
"No significant difference in the other treatment groups."1.48Are we missing hypoglycaemia? Elderly patients with insulin-treated diabetes present to primary care frequently with non-specific symptoms associated with hypoglycaemia. ( Hamilton, W; Hattersley, AT; Hope, SV; Shields, BM; Taylor, PJ, 2018)

Research

Studies (41)

TimeframeStudies, this research(%)All Research%
pre-19902 (4.88)18.7374
1990's0 (0.00)18.2507
2000's5 (12.20)29.6817
2010's24 (58.54)24.3611
2020's10 (24.39)2.80

Authors

AuthorsStudies
Mehrpour, O1
Saeedi, F1
Hoyte, C1
Hadianfar, A1
Nakhaee, S1
Brent, J1
Rueda Prada, L1
Knopps, L1
Dumic, I1
Barusya, C1
Subramanian, A1
Charokopos, A1
Zurob, AS1
Nabrdalik, K1
Skonieczna-Żydecka, K1
Irlik, K1
Hendel, M1
Kwiendacz, H1
Łoniewski, I1
Januszkiewicz, K1
Gumprecht, J1
Lip, GYH1
Agarwal, SM1
Stogios, N1
Ahsan, ZA1
Lockwood, JT1
Duncan, MJ1
Takeuchi, H1
Cohn, T1
Taylor, VH1
Remington, G1
Faulkner, GEJ1
Hahn, M1
Salamah, HM1
Marey, A1
Elsayed, E1
Hasan, MT1
Mahmoud, A1
Abualkhair, KA1
Abo-Elnour, DE1
Abdelhaleem, IA1
Abd-Elgawad, M1
Zinman, B2
Aroda, VR1
Buse, JB1
Cariou, B1
Harris, SB1
Hoff, ST1
Pedersen, KB1
Tarp-Johansen, MJ1
Araki, E1
Gulati, S1
Desai, J1
Palackdharry, SM1
Morris, JC1
Zhu, Z1
Jandarov, R1
Riaz, MK1
Takiar, V1
Mierzwa, M1
Gutkind, JS1
Molinolo, A1
Desai, PB1
Sadraei, NH1
Wise-Draper, TM1
Patoulias, D1
Katsimardou, A1
Kalogirou, MS1
Zografou, I1
Toumpourleka, M1
Imprialos, K1
Stavropoulos, K1
Stergiou, I1
Papadopoulos, C1
Doumas, M1
Tabesh, M1
Hachem, M1
Lau, LH1
Borschmann, K1
Churilov, L1
Price, SAL1
Sumithran, P1
Donnan, G1
Zajac, J1
Thijs, V1
Ekinci, EI1
Yeku, OO1
Medford, AJ1
Fenves, AZ1
Uljon, SN1
Frías, JP1
Davies, MJ1
Rosenstock, J1
Pérez Manghi, FC1
Fernández Landó, L1
Bergman, BK1
Liu, B1
Cui, X1
Brown, K1
Hope, SV1
Taylor, PJ1
Shields, BM1
Hattersley, AT1
Hamilton, W1
Wysham, C1
Grimm, M1
Chen, S1
Matyjaszek-Matuszek, B1
Lenart-Lipińska, M1
Rogalska, D1
Nowakowski, A1
Yu Pan, C1
Han, P1
Liu, X1
Yan, S1
Feng, P1
Zhou, Z1
Lv, X3
Tian, H1
Jin Kui, Y1
Su, B1
Shang, S1
Niemoeller, E1
Sayed, R1
Saad, AS1
El Wakeel, L1
Elkholy, E1
Badary, O1
Chen, X1
Yang, G1
Lu, D1
Piao, C1
Zhang, X1
Jiang, H1
Xie, Y1
Yang, J2
Li, X1
Li, Y3
Xiao, X1
Sun, L1
Zheng, S1
Cheng, Q1
Peng, Y2
Yang, W1
Zang, L1
Liu, Y1
Geng, J1
Luo, Y1
Bian, F1
Liu, J1
Sun, Y1
Bosch-Traberg, H1
Mu, Y1
Kim, SS1
Kim, IJ1
Lee, KJ1
Park, JH1
Kim, YI1
Lee, YS1
Chung, SC1
Lee, SJ1
Bailey, TS1
Takács, R1
Tinahones, FJ1
Rao, PV1
Tsoukas, GM1
Thomsen, AB2
Kaltoft, MS1
Maislos, M1
Broglio, F1
Mannucci, E1
Napoli, R1
Nicolucci, A1
Purrello, F1
Nikonova, E1
Stager, W1
Trevisan, R1
Bettge, K1
Kahle, M1
Abd El Aziz, MS1
Meier, JJ1
Nauck, MA2
Pelletier, AL1
Butler, AM1
Gillies, RA1
May, JR1
Ratner, R1
Nauck, M1
Kapitza, C1
Asnaghi, V1
Boldrin, M2
Balena, R2
Liutkus, J1
Rosas Guzman, J1
Norwood, P1
Pop, L1
Northrup, J1
Cao, D1
Trautmann, M1
Li, XJ1
Yu, YX1
Liu, CQ1
Zhang, W1
Zhang, HJ1
Yan, B1
Wang, LY1
Yang, SY1
Zhang, SH1
Samson, SL1
Sathyanarayana, P1
Jogi, M1
Gonzalez, EV1
Gutierrez, A1
Krishnamurthy, R1
Muthupillai, R1
Chan, L1
Bajaj, M1
Pujante Alarcón, P1
Hellín Gil, MD1
Román, LM1
Ferrer Gómez, M1
García Zafra, MV1
Tébar Massó, J1
Gough, SC1
Pratley, RE2
Bailey, T1
Montanya, E1
Filetti, S1
Garber, AJ1
Furber, S1
Davies, M1
Yuan, GH1
Song, WL1
Huang, YY1
Guo, XH1
Gao, Y1
Flaherty, AM1
Urosevic, D1
Bhavsar, S1
Mudaliar, S1
Cherrington, A1
Hollander, P1
Maggs, DG1
Ruggles, JA1
Fineman, M1
Shen, L1
Kolterman, OG1
Weyer, C1
Fujioka, K1
Brazg, RL1
Raz, I1
Bruce, S1
Joyal, S1
Swanink, R1
Pans, M1
Hoogwerf, BJ1
Durán García, S1
Milton, DR1
Giaconia, JM1
Kim, DD1
Trautmann, ME1
Brodows, RG1
Stades, AM1
Holleman, F1
Hoekstra, JB1
Munro, JF1
MacCuish, AC1
Marshall, A1
Wilson, EM1
Duncan, LJ1
Heikinheimo, R1

Clinical Trials (12)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Comparison of Bupropion SR and Placebo for Smoking Cessation[NCT00176449]Phase 452 participants (Actual)Interventional2001-04-30Completed
Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Insulin. A 52-week, Randomised, Double-blind, Placebo-controlled Trial (PIONEER 8 - Insulin add-on)[NCT03021187]Phase 3731 participants (Actual)Interventional2017-02-02Completed
A Phase 3, Randomized, Open-Label Trial Comparing Efficacy and Safety of Tirzepatide Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Patients With Type 2 Diabetes[NCT03987919]Phase 31,879 participants (Actual)Interventional2019-07-30Completed
Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Mellitus Insufficiently Controlled by Metformin (With or Without Sulfonylurea): a Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study With 24-week Treatment P[NCT01169779]Phase 3391 participants (Actual)Interventional2010-07-31Completed
The Efficacy and Safety of Liraglutide Compared to Sitagliptin, Both in Combination With Metformin in Chinese Subjects With Type 2 Diabetes.(LIRA-DPP-4 CHINA™)[NCT02008682]Phase 4368 participants (Actual)Interventional2013-12-31Completed
A Multicenter, Randomized, Double Blind Study to Compare the Efficacy and Safety of Sitagliptin/Metformin Fixed-Dose Combination (Janumet®) Compared to Glimepiride in Patients With Type 2 Diabetes Mellitus[NCT00993187]Phase 4292 participants (Actual)Interventional2010-05-04Completed
Efficacy and Safety of Switching From Sitagliptin to Liraglutide in Subjects With Type 2 Diabetes Not Achieving Adequate Glycaemic Control on Sitagliptin and Metformin[NCT01907854]Phase 4407 participants (Actual)Interventional2013-12-02Completed
A Double-blind, Placebo-controlled Titration Study to Investigate the Tolerability, Safety and Pharmacodynamic Profile of a GLP-1 Analogue in Patients With Type 2 Diabetes Mellitus Treated With a Stable Dose of Metformin.[NCT00460941]Phase 2133 participants (Actual)Interventional2007-04-30Completed
Safety and Efficacy of Exenatide in Patients With Type 2 Diabetes Using a Thiazolidinedione or a Thiazolidinedione and Metformin[NCT00603239]Phase 3165 participants (Actual)Interventional2008-01-31Completed
Effect of Exenatide Treatment on Hepatic Fat Content and Plasma Adipocytokine Levels in Patients With Type 2 Diabetes Mellitus[NCT01432405]Phase 424 participants (Actual)Interventional2007-06-30Completed
The Effect of Liraglutide Compared to Sitagliptin, Both in Combination With Metformin in Subjects With Type 2 Diabetes. A 26-week, Randomised, Open-label, Active Comparator, Three-armed, Parallel-group, Multi-centre, Multinational Trial With a 52-week Ext[NCT00700817]Phase 3665 participants (Actual)Interventional2008-06-30Completed
Safety and Efficacy of Exenatide in Patients With Type 2 Diabetes Using Thiazolidinediones or Thiazolidinediones and Metformin[NCT00099320]Phase 3182 participants (Actual)Interventional2004-05-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Change in Body Weight (kg) (Week 52)

Change from baseline (week 0) in body weight to week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 52

InterventionKg (Mean)
Oral Semaglutide 3 mg-0.9
Oral Semaglutide 7 mg-2.2
Oral Semaglutide 14 mg-3.8
Placebo0.5

Change in HbA1c (Week 52)

Change from baseline (week 0) in HbA1c to week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 52

InterventionPercentage of HbA1c (Mean)
Oral Semaglutide 3 mg-0.6
Oral Semaglutide 7 mg-0.9
Oral Semaglutide 14 mg-1.2
Placebo-0.2

Number of Treatment-emergent Adverse Events (TEAEs) During Exposure to Trial Product

Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 57 (52-week treatment period plus the 5-week follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. (NCT03021187)
Timeframe: Weeks 0-57

InterventionEvents (Number)
Oral Semaglutide 3 mg626
Oral Semaglutide 7 mg555
Oral Semaglutide 14 mg586
Placebo464

Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during week 0 to week 57 (52-week treatment period plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. (NCT03021187)
Timeframe: Weeks 0-57

InterventionEpisodes (Number)
Oral Semaglutide 3 mg196
Oral Semaglutide 7 mg180
Oral Semaglutide 14 mg147
Placebo156

Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during week 0 to week 57 (52-week treatment period plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. (NCT03021187)
Timeframe: Weeks 0-57

InterventionParticipants (Count of Participants)
Oral Semaglutide 3 mg52
Oral Semaglutide 7 mg47
Oral Semaglutide 14 mg48
Placebo54

Change in Amylase - Ratio to Baseline

Change from baseline (week 0) in amylase (units/litre (U/L)) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionRatio of amylase (Geometric Mean)
Week 26Week 52
Oral Semaglutide 14 mg1.141.17
Oral Semaglutide 3 mg1.081.07
Oral Semaglutide 7 mg1.121.11
Placebo1.010.99

Change in Body Mass Index

Change from baseline (week 0) in body mass index (BMI) was evaluated at weeks 26 and 52. BMI was calculated based on body weight and height based on the formula: BMI kg/m^2 = body weight (kg)/(Height (m) x Height (m)). Data based on in-trial observation period is presented. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
Interventionkg/m^2 (Mean)
Week 26Week 52
Oral Semaglutide 14 mg-1.4-1.4
Oral Semaglutide 3 mg-0.5-0.3
Oral Semaglutide 7 mg-1.0-0.8
Placebo-0.20.2

Change in Body Weight (Percentage)

Relative change from baseline (week 0) in body weight (%) was evaluated at weeks 26 and 52.The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionPercentage change (Mean)
Week 26Week 52
Oral Semaglutide 14 mg-4.30-4.42
Oral Semaglutide 3 mg-1.73-1.18
Oral Semaglutide 7 mg-3.11-2.54
Placebo-0.470.65

Change in Body Weight (Week 26)

Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. The endpoint was also evaluated based on data from the on-treatment without rescue medication observation period. It started at the date of first dose of trial product and excluded the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26

,,,
InterventionKg (Mean)
In trialOn-treatment without rescue medication
Oral Semaglutide 14 mg-3.7-3.9
Oral Semaglutide 3 mg-1.4-1.5
Oral Semaglutide 7 mg-2.6-3.0
Placebo-0.5-0.5

Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed)

"Change from baseline (week 0) in Diabetes Treatment Satisfaction Questionnaire - status version (DTSQs) was evaluated at week 26 and week 52. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of hyperglycaemia and hypoglycaemia, respectively. Thus, lower scores indicate a perception of blood glucose levels being none of the time unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score has a minimum of 0 and a maximum of 36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction." (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionScore on a scale (Mean)
Satisfaction with treatment: wk 26Satisfaction with treatment: wk 52Feeling of unacceptably high blood sugars: wk 26Feeling of unacceptably high blood sugars: wk 52Feeling of unacceptably low blood sugars: wk 26Feeling of unacceptably low blood sugars: wk 52Convenience of treatment: wk 26Convenience of treatment: wk 52Flexibility of treatment: wk 26Flexibility of treatment: wk 52Satisfaction with understading of diabetes: wk 26Satisfaction with understading of diabetes: wk 52Recommending treatment to others: wk 26Recommending treatment to others: wk 52Satisfaction to continue present treatment: wk 26Satisfaction to continue present treatment: wk 52Total treatment satisfaction: wk 26Total treatmemt satisfaction: wk 52
Oral Semaglutide 14 mg0.630.78-1.29-1.340.13-0.060.500.440.400.460.270.340.530.650.580.652.903.32
Oral Semaglutide 3 mg0.470.53-0.62-0.700.070.040.510.380.310.250.240.250.200.320.400.412.122.14
Oral Semaglutide 7 mg0.590.51-1.23-1.15-0.06-0.100.500.520.370.420.310.350.660.630.570.563.002.99
Placebo0.180.20-0.28-0.41-0.15-0.020.200.190.230.230.040.030.02-0.010.090.030.760.67

Change in ECG Evaluation

Change from baseline (week 0) in electrocardiogram (ECG) was evaluated at weeks 26 and 52. Change from baseline results are presented as shift in findings (normal; abnormal and not clinically significant (NCS); abnormal and clinically significant (CS)) from week 0 to week 26 and 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionParticipants (Count of Participants)
Normal (week 0) to Normal (week 26)Normal (week 0) to Abnormal NCS (week 26)Normal (week 0) to Abnormal CS (week 26)Abnormal NCS (week 0) to Normal (week 26)Abnormal NCS (week 0) to Abnormal NCS (week 26)Abnormal NCS (week 0) to Abnormal CS (week 26)Abnormal CS (week 0) to Normal (week 26)Abnormal CS (week 0) to Abnormal NCS (week 26)Abnormal CS (week 0) to Abnormal CS (week 26)Normal (week 0) to Normal (week 52)Normal (week 0) to Abnormal NCS (week 52)Normal (week 0) to Abnormal CS (week 52)Abnormal NCS to Normal (Week 52)Abnormal NCS to Abnormal NCS (Week 52)Abnormal NCS to Abnormal CS (Week 52)Abnormal CS to Normal (Week 52)Abnormal CS to Abnormal NCS (Week 52)Abnormal CS to Abnormal CS (Week 52)
Oral Semaglutide 14 mg90170164701118520119420021
Oral Semaglutide 3 mg101100224400009514213500000
Oral Semaglutide 7 mg98120174200049115217401004
Placebo93120195101018417121471011

Change in Fasting Plasma Glucose (FPG)

Change from baseline (week 0) in FPG to week 26 and week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
Interventionmmol/L (Mean)
Week 26Week 52
Oral Semaglutide 14 mg-1.36-1.60
Oral Semaglutide 3 mg-0.45-0.81
Oral Semaglutide 7 mg-1.14-1.12
Placebo0.51-0.09

Change in HbA1c (Week 26)

Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 26. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. The endpoint was also analysed based on data from the on-treatment without rescue medication observation period. On-treatment without rescue medication observation period started at the date of the first dose of trial product and includes the period after initiation of rescue medication, if any, and excludes the period after premature trial discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26

,,,
InterventionPercentage of HbA1c (Mean)
In-trialOn-treatment without rescue medication
Oral Semaglutide 14 mg-1.3-1.4
Oral Semaglutide 3 mg-0.5-0.6
Oral Semaglutide 7 mg-1.0-1.1
Placebo-0.1-0.1

Change in HDL Cholesterol - Ratio to Baseline

Change from baseline (week 0) in HDL cholesterol (mmol/L) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionRatio of HDL cholesterol (Geometric Mean)
Week 26Week 52
Oral Semaglutide 14 mg0.981.01
Oral Semaglutide 3 mg1.001.01
Oral Semaglutide 7 mg0.980.98
Placebo1.011.00

Change in IWQoL-Lite-CT: Total Score and Scores From the 4 Domains

The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. The items of the IWQOL-Lite-CT pertain to physical functioning (physical, physical function and pain/discomfort) and psychosocial domains and all items employ a 5-point graded response scale (never, rarely, sometimes, usually, always; or not at all true, a little true, moderately true, mostly true, completely true). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. Results are based on the data from the in-trial observation period, which started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionScore on a scale (Mean)
1) Psychosocial (Week 26)1) Psychosocial (Week 52)2) Physical (Week 26)2) Physical (Week 52)3) Physical function(Week 26)3) Physical function(Week 52)4) Pain/discomfort (Week 26)4) Pain/discomfort (Week 52)5) IWQOL-Lite-CT Total (Week 26)5) IWQOL-Lite-CT Total (Week 52)
Oral Semaglutide 14 mg4.105.352.152.502.512.591.232.283.414.35
Oral Semaglutide 3 mg1.451.962.293.101.883.453.302.231.742.35
Oral Semaglutide 7 mg-0.32-0.92-0.66-0.53-0.35-0.59-1.45-0.37-0.45-0.79
Placebo-0.49-0.46-1.75-1.24-1.70-0.98-1.85-1.88-0.94-0.73

Change in LDL Cholesterol - Ratio to Baseline

Change from baseline in LDL cholesterol (mmol/L) is presented as ratio to baseline at week 26 and week 52. Results are based on the data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionRatio of LDL cholesterol (Geometric Mean)
Week 26Week 52
Oral Semaglutide 14 mg0.930.95
Oral Semaglutide 3 mg0.980.97
Oral Semaglutide 7 mg0.930.96
Placebo1.031.00

Change in Lipase - Ratio to Baseline

Change from baseline (week 0) in lipase (units/litre (U/L)) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionRatio of lipase (Geometric Mean)
Week 26Week 52
Oral Semaglutide 14 mg1.351.35
Oral Semaglutide 3 mg1.141.09
Oral Semaglutide 7 mg1.341.25
Placebo0.990.99

Change in Pulse Rate

Change from baseline (week 0) in pulse rate was evaluated at weeks 26 and 52 Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionBeats/minute (Mean)
Week 26Week 52
Oral Semaglutide 14 mg32
Oral Semaglutide 3 mg1-0
Oral Semaglutide 7 mg21
Placebo-00

Change in SBP and DBP

Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at weeks 26 and 52 Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionmmHg (Mean)
SBP: Week 26SBP: Week 52DBP: Week 26DBP: Week 52
Oral Semaglutide 14 mg-5-6-1-2
Oral Semaglutide 3 mg-1-1-0-1
Oral Semaglutide 7 mg-3-3-1-2
Placebo100-0

Change in Self-measured Plasma Glucose (SMPG) Mean 7-point Profile

Change from baseline (week 0) in self-measured plasma glucose (SMPG) mean 7-point profile to week 26 and week 52. SMPG was recorded at the following 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after dinner and at bedtime. Mean 7-point profile was defined as the area under the profile, calculated using the trapezoidal method, divided by the measurement time. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
Interventionmmol/L (Mean)
Week 26Week 52
Oral Semaglutide 14 mg-2.0-2.0
Oral Semaglutide 3 mg-1.2-1.6
Oral Semaglutide 7 mg-1.8-1.7
Placebo-0.3-0.9

Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)

SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at weeks 26 and 52. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionScore on a scale (Mean)
1) Physical functioning (Week 26)1) Physical functioning (Week 52)2) Role Physical (Week 26)2) Role Physical (Week 52)3) Bodily Pain (Week 26)3) Bodily Pain (Week 52)4) General Health (Week 26)4) General Health (Week 52)5) Vitality (Week 26)5) Vitality (Week 52)6) Social functioning (Week 26)6) Social functioning (Week 52)7) Role emotional (Week 26)7) Role emotional (Week 52)8) Mental health (Week 26)8) Mental health (Week 52)9) Physical component summary (Week 26)9) Physical component summary (Week 52)10) Mental component summary (Week 26)10) Mental component summary (Week 52)
Oral Semaglutide 14 mg-0.07-0.320.04-0.87-0.18-0.211.261.380.140.70-0.510.030.240.090.990.89-0.02-0.360.490.82
Oral Semaglutide 3 mg0.530.51-0.320.00-0.02-0.401.430.92-0.56-0.53-0.310.11-0.940.77-1.41-0.480.940.26-1.41-0.09
Oral Semaglutide 7 mg0.52-0.40-0.43-0.761.470.560.700.75-1.27-1.430.34-0.610.62-0.34-0.82-0.740.750.12-0.55-0.89
Placebo-0.82-0.77-0.39-0.93-0.72-0.64-0.36-1.43-1.69-1.09-1.10-1.74-1.50-2.78-2.32-1.30-0.05-0.41-2.16-2.19

Change in SMPG Mean Postprandial Increment Over All Meals

Change from baseline (week 0) in SMPG mean postprandial increment over all meals to week 26 and week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
Interventionmmol/L (Mean)
Week 26Week 52
Oral Semaglutide 14 mg-1.2-0.7
Oral Semaglutide 3 mg-0.3-0.3
Oral Semaglutide 7 mg-0.8-0.7
Placebo-0.1-0.3

Change in Total Cholesterol - Ratio to Baseline

Change from baseline in total cholesterol (mmol/L) is presented as ratio to baseline at week 26 and week 52. Results are based on the data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionRatio of total cholesterol (Geometric Mean)
Week 26Week 52
Oral Semaglutide 14 mg0.950.95
Oral Semaglutide 3 mg0.990.98
Oral Semaglutide 7 mg0.950.97
Placebo1.031.00

Change in Total Daily Insulin Dose

Change from baseline in total daily insulin dose to week 26 and week 52 is presented. Results are based on the data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionUnits/day (Mean)
Week 26Week 52
Oral Semaglutide 14 mg-8-5
Oral Semaglutide 3 mg-51
Oral Semaglutide 7 mg-9-8
Placebo-28

Change in Triglycerides - Ratio to Baseline

Change from baseline (week 0) in triglycerides (mmol/L) at weeks 26 and 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
InterventionRatio of triglycerides (Geometric Mean)
Week 26Week 52
Oral Semaglutide 14 mg0.910.86
Oral Semaglutide 3 mg0.970.93
Oral Semaglutide 7 mg0.920.94
Placebo0.990.97

Change in Waist Circumference

Change from baseline (week 0) in waist circumference was evaluated at weeks 26 and 52.The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 0, week 26, week 52

,,,
Interventioncm (Mean)
Week 26Week 52
Oral Semaglutide 14 mg-3.6-4.0
Oral Semaglutide 3 mg-0.9-0.8
Oral Semaglutide 7 mg-2.3-2.3
Placebo-0.60.3

Semaglutide Plasma Concentrations for Population PK Analyses

This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Semaglutide plasma concentrations were measured at week 4, 14, 26, 38 and 52. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. (NCT03021187)
Timeframe: Weeks 0-52

,,
Interventionnmol/L (Geometric Mean)
Week 4Week 14Week 26Week 38Week 52
Oral Semaglutide 14 mg2.914.512.610.811.9
Oral Semaglutide 3 mg2.92.92.72.52.4
Oral Semaglutide 7 mg2.97.57.26.95.8

Time to Additional Anti-diabetic Medication

Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the periods, from week 0 to week 26 and week 0 to week 52. Additional anti-diabetic medication was defined as use of new anti-diabetic medication for more than 21 days with the initiation at or after randomisation (week 0) and before (planned) end-of-treatment (week 52), and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. (NCT03021187)
Timeframe: Weeks 0-52

,,,
InterventionParticipants (Count of Participants)
Week 0-26Week 0-52
Oral Semaglutide 14 mg844
Oral Semaglutide 3 mg961
Oral Semaglutide 7 mg845
Placebo1175

Time to Rescue Medication

Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 0 to week 26 and week 0 to week 52. Rescue medication was defined as use of new anti-diabetic medication as add-on to trial product and used for more than 21 days with the initiation at or after randomisation (week 1) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation. (NCT03021187)
Timeframe: Weeks 0-52

,,,
InterventionParticipants (Count of Participants)
Week 0-26Week 0-52
Oral Semaglutide 14 mg431
Oral Semaglutide 3 mg554
Oral Semaglutide 7 mg233
Placebo967

Change in Eye Examination Category

Participants with eye examination (fundoscopy) findings, normal, abnormal NCS and abnormal CS at baseline (week -2) and week 52 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. (NCT03021187)
Timeframe: Week -2, week 52

InterventionParticipants (Count of Participants)
Left eye (week -2)72577392Left eye (week -2)72577393Left eye (week -2)72577394Left eye (week -2)72577395Left eye (week 52)72577392Left eye (week 52)72577393Left eye (week 52)72577394Left eye (week 52)72577395Right eye (week -2)72577392Right eye (week -2)72577393Right eye (week -2)72577394Right eye (week -2)72577395Right eye (week 52)72577392Right eye (week 52)72577393Right eye (week 52)72577394Right eye (week 52)72577395
NormalAbnormal NCSAbnormal CS
Oral Semaglutide 3 mg89
Placebo108
Oral Semaglutide 7 mg64
Placebo55
Oral Semaglutide 3 mg19
Placebo21
Oral Semaglutide 3 mg83
Oral Semaglutide 7 mg102
Oral Semaglutide 14 mg92
Placebo88
Oral Semaglutide 3 mg65
Oral Semaglutide 7 mg51
Oral Semaglutide 14 mg52
Placebo53
Oral Semaglutide 3 mg22
Placebo25
Oral Semaglutide 3 mg85
Oral Semaglutide 7 mg104
Oral Semaglutide 14 mg99
Placebo106
Oral Semaglutide 3 mg76
Oral Semaglutide 7 mg63
Oral Semaglutide 14 mg64
Placebo58
Oral Semaglutide 7 mg13
Oral Semaglutide 14 mg18
Placebo20
Oral Semaglutide 3 mg79
Oral Semaglutide 7 mg99
Oral Semaglutide 14 mg97
Placebo90
Oral Semaglutide 3 mg67
Oral Semaglutide 7 mg54
Oral Semaglutide 14 mg51
Placebo50
Oral Semaglutide 3 mg23
Oral Semaglutide 7 mg14
Oral Semaglutide 14 mg15
Placebo26

Change in Physical Examination

Participants with physical examination findings, normal, abnormal NCS and abnormal CS at baseline (weeks -2) and weeks 52 presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. Results are presented for the following examinations: 1) Cardiovascular system; 2) Central and peripheral nervous system; 3) Gastrointestinal system, incl. mouth; 4) General appearance; 5) Head, ears, eyes, nose, throat, neck; 6) Lymph node palpation; 7) Musculoskeletal system; 8) Respiratory system; 9) Skin; 10) Thyroid gland. (NCT03021187)
Timeframe: Week -2, week 52

InterventionParticipants (Count of Participants)
1) Cardiovascular system (week -2)725773921) Cardiovascular system (week -2)725773931) Cardiovascular system (week -2)725773941) Cardiovascular system (week -2)725773951) Cardiovascular system (week 52)725773921) Cardiovascular system (week 52)725773931) Cardiovascular system (week 52)725773941) Cardiovascular system (week 52)725773952) Central and peripheral nervous system (week -2)725773922) Central and peripheral nervous system (week -2)725773952) Central and peripheral nervous system (week -2)725773932) Central and peripheral nervous system (week -2)725773942) Central and peripheral nervous system (week 52)725773922) Central and peripheral nervous system (week 52)725773932) Central and peripheral nervous system (week 52)725773942) Central and peripheral nervous system (week 52)725773953) Gastrointestinal system, incl. mouth (week -2)725773933) Gastrointestinal system, incl. mouth (week -2)725773953) Gastrointestinal system, incl. mouth (week -2)725773923) Gastrointestinal system, incl. mouth (week -2)725773943) Gastrointestinal system, incl. mouth (week 52)725773923) Gastrointestinal system, incl. mouth (week 52)725773933) Gastrointestinal system, incl. mouth (week 52)725773953) Gastrointestinal system, incl. mouth (week 52)725773944) General appearance (week -2)725773924) General appearance (week -2)725773934) General appearance (week -2)725773944) General appearance (week -2)725773954) General appearance (week 52)725773924) General appearance (week 52)725773934) General appearance (week 52)725773944) General appearance (week 52)725773955) Head, ears, eyes, nose, throat, neck (week -2)725773925) Head, ears, eyes, nose, throat, neck (week -2)725773935) Head, ears, eyes, nose, throat, neck (week -2)725773945) Head, ears, eyes, nose, throat, neck (week -2)725773955) Head, ears, eyes, nose, throat, neck (week 52)725773925) Head, ears, eyes, nose, throat, neck (week 52)725773935) Head, ears, eyes, nose, throat, neck (week 52)725773945) Head, ears, eyes, nose, throat, neck (week 52)725773956) Lymph node palpation (week -2)725773926) Lymph node palpation (week -2)725773936) Lymph node palpation (week -2)725773946) Lymph node palpation (week -2)725773956) Lymph node palpation (week 52)725773926) Lymph node palpation (week 52)725773936) Lymph node palpation (week 52)725773946) Lymph node palpation (week 52)725773957) Musculoskeletal system (week -2)725773927) Musculoskeletal system (week -2)725773937) Musculoskeletal system (week -2)725773957) Musculoskeletal system (week -2)725773947) Musculoskeletal system (week 52)725773927) Musculoskeletal system (week 52)725773937) Musculoskeletal system (week 52)725773947) Musculoskeletal system (week 52)725773958) Respiratory system (week -2)725773928) Respiratory system (week -2)725773938) Respiratory system (week -2)725773948) Respiratory system (week -2)725773958) Respiratory system (week 52)725773928) Respiratory system (week 52)725773938) Respiratory system (week 52)725773948) Respiratory system (week 52)725773959) Skin (week -2)725773929) Skin (week -2)725773939) Skin (week -2)725773949) Skin (week -2)725773959) Skin (week 52)725773929) Skin (week 52)725773939) Skin (week 52)725773949) Skin (week 52)7257739510) Thyroid gland (week -2)7257739310) Thyroid gland (week -2)7257739210) Thyroid gland (week -2)7257739410) Thyroid gland (week -2)7257739510) Thyroid gland (week 52)7257739310) Thyroid gland (week 52)7257739210) Thyroid gland (week 52)7257739410) Thyroid gland (week 52)72577395
Abnormal NCSNormalAbnormal CS
Oral Semaglutide 3 mg166
Oral Semaglutide 7 mg166
Oral Semaglutide 14 mg157
Placebo170
Oral Semaglutide 3 mg18
Oral Semaglutide 7 mg15
Placebo14
Oral Semaglutide 3 mg157
Oral Semaglutide 7 mg158
Oral Semaglutide 14 mg145
Placebo160
Oral Semaglutide 3 mg17
Oral Semaglutide 7 mg12
Oral Semaglutide 14 mg24
Placebo12
Oral Semaglutide 3 mg158
Oral Semaglutide 7 mg157
Oral Semaglutide 14 mg158
Placebo163
Oral Semaglutide 3 mg26
Oral Semaglutide 7 mg24
Oral Semaglutide 3 mg149
Oral Semaglutide 7 mg150
Oral Semaglutide 14 mg147
Oral Semaglutide 3 mg25
Oral Semaglutide 7 mg20
Oral Semaglutide 14 mg22
Oral Semaglutide 7 mg175
Oral Semaglutide 14 mg177
Placebo180
Oral Semaglutide 14 mg4
Placebo4
Oral Semaglutide 3 mg163
Oral Semaglutide 14 mg166
Placebo171
Oral Semaglutide 3 mg9
Oral Semaglutide 3 mg159
Oral Semaglutide 7 mg162
Oral Semaglutide 14 mg160
Oral Semaglutide 7 mg18
Oral Semaglutide 14 mg21
Placebo22
Oral Semaglutide 3 mg151
Oral Semaglutide 7 mg148
Oral Semaglutide 14 mg153
Placebo152
Oral Semaglutide 3 mg23
Oral Semaglutide 7 mg21
Oral Semaglutide 14 mg17
Oral Semaglutide 3 mg168
Oral Semaglutide 7 mg173
Oral Semaglutide 14 mg172
Placebo178
Oral Semaglutide 3 mg15
Oral Semaglutide 7 mg8
Oral Semaglutide 14 mg7
Oral Semaglutide 3 mg161
Oral Semaglutide 14 mg165
Placebo166
Placebo5
Oral Semaglutide 14 mg2
Placebo2
Oral Semaglutide 3 mg184
Oral Semaglutide 7 mg181
Oral Semaglutide 14 mg181
Oral Semaglutide 3 mg172
Placebo172
Oral Semaglutide 3 mg0
Oral Semaglutide 3 mg171
Oral Semaglutide 7 mg170
Oral Semaglutide 14 mg169
Placebo175
Oral Semaglutide 3 mg13
Oral Semaglutide 7 mg10
Oral Semaglutide 14 mg9
Placebo9
Oral Semaglutide 3 mg160
Oral Semaglutide 7 mg160
Placebo164
Oral Semaglutide 3 mg11
Oral Semaglutide 7 mg9
Oral Semaglutide 14 mg8
Placebo8
Oral Semaglutide 3 mg3
Oral Semaglutide 7 mg1
Oral Semaglutide 14 mg3
Oral Semaglutide 3 mg182
Oral Semaglutide 7 mg177
Oral Semaglutide 14 mg180
Placebo184
Oral Semaglutide 3 mg1
Oral Semaglutide 7 mg4
Oral Semaglutide 3 mg173
Oral Semaglutide 7 mg164
Oral Semaglutide 14 mg170
Placebo173
Oral Semaglutide 7 mg6
Oral Semaglutide 3 mg156
Oral Semaglutide 7 mg153
Oral Semaglutide 14 mg159
Placebo162
Oral Semaglutide 3 mg27
Oral Semaglutide 7 mg28
Placebo21
Oral Semaglutide 14 mg0
Placebo1
Oral Semaglutide 3 mg152
Oral Semaglutide 7 mg144
Oral Semaglutide 14 mg151
Placebo155
Oral Semaglutide 3 mg20
Oral Semaglutide 7 mg26
Oral Semaglutide 14 mg18
Placebo18
Oral Semaglutide 3 mg2
Oral Semaglutide 7 mg0
Oral Semaglutide 14 mg1
Placebo0
Oral Semaglutide 3 mg177
Oral Semaglutide 7 mg176
Oral Semaglutide 14 mg176
Placebo177
Oral Semaglutide 3 mg7
Oral Semaglutide 7 mg5
Oral Semaglutide 14 mg5
Oral Semaglutide 7 mg165
Oral Semaglutide 14 mg168
Oral Semaglutide 3 mg8
Placebo6

Participants Who Achieve Body Weight Loss ≥10% (Yes/no)

Participants who achieved weight loss more than or equal to 10% of their baseline body weight (yes/no) at weeks 26 and 52 are presented. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. Results are based on the data from the in-trial observation period, which started at the date of randomisation and included the period after initiatiion of of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 26, week 52

InterventionParticipants (Count of Participants)
Week 2672577393Week 2672577394Week 2672577395Week 2672577392Week 5272577392Week 5272577393Week 5272577395Week 5272577394
YesNo
Oral Semaglutide 3 mg2
Oral Semaglutide 7 mg12
Oral Semaglutide 14 mg19
Placebo1
Oral Semaglutide 3 mg175
Oral Semaglutide 7 mg162
Oral Semaglutide 14 mg154
Placebo176
Oral Semaglutide 3 mg4
Oral Semaglutide 7 mg17
Oral Semaglutide 14 mg21
Oral Semaglutide 3 mg170
Oral Semaglutide 7 mg154
Oral Semaglutide 14 mg149
Placebo172

Participants Who Achieve Body Weight Loss ≥5% (Yes/no)

Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 26 and 52 are presented. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 26, week 52

InterventionParticipants (Count of Participants)
Week 2672577392Week 2672577393Week 2672577394Week 2672577395Week 5272577395Week 5272577392Week 5272577393Week 5272577394
YesNo
Oral Semaglutide 3 mg23
Oral Semaglutide 7 mg53
Placebo5
Oral Semaglutide 3 mg154
Oral Semaglutide 7 mg121
Oral Semaglutide 14 mg106
Placebo172
Oral Semaglutide 3 mg30
Oral Semaglutide 7 mg48
Oral Semaglutide 14 mg67
Placebo9
Oral Semaglutide 3 mg144
Oral Semaglutide 7 mg123
Oral Semaglutide 14 mg103
Placebo164

Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)

Participants who achieved HbA1c less than 7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at weeks 26 and 52 are presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. (NCT03021187)
Timeframe: Week 26, week 52

InterventionParticipants (Count of Participants)
Week 2672577392Week 2672577394Week 2672577393Week 2672577395Week 5272577392Week 5272577393Week 5272577394Week 5272577395
YesNo
Oral Semaglutide 3 mg32
Oral Semaglutide 7 mg47
Oral Semaglutide 14 mg76
Placebo4
Oral Semaglutide 3 mg144
Oral Semaglutide 7 mg127
Oral Semaglutide 14 mg97
Placebo172
Oral Semaglutide 3 mg27
Oral Semaglutide 7 mg43
Oral Semaglutide 14 mg61
Placebo8
Oral Semaglutide 3 mg146
Oral Semaglutide 7 mg126
Oral Semaglutide 14 mg107
Placebo164

Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)

Participants who achieved HbA1c reduction more than or equal to 1% of their baseline HbA1c and weight loss of more than or equal to 3% of their baseline body weight (yes/no) at weeks 26 and 52 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. (NCT03021187)
Timeframe: Week 26, week 52

InterventionParticipants (Count of Participants)
Week 2672577392Week 2672577395Week 2672577393Week 2672577394Week 5272577395Week 5272577392Week 5272577393Week 5272577394
YesNo
Oral Semaglutide 3 mg28
Oral Semaglutide 7 mg51
Oral Semaglutide 14 mg76
Placebo7
Oral Semaglutide 3 mg148
Oral Semaglutide 7 mg123
Oral Semaglutide 14 mg97
Placebo169
Oral Semaglutide 3 mg20
Oral Semaglutide 7 mg37
Oral Semaglutide 14 mg64
Placebo5
Oral Semaglutide 3 mg153
Oral Semaglutide 7 mg132
Oral Semaglutide 14 mg104
Placebo167

Participants Who Achieve: HbA1c < 7.0% (53 mmol/Mol) (American Diabetes Association (ADA) Target) (Yes/no)

Number of particpants achieving HbA1c < 7.0 % (53 mmol/mol) according to American Diabetes Association (ADA) target, at week 26 and week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 26, week 52

InterventionParticipants (Count of Participants)
Week 2672577394Week 2672577395Week 2672577392Week 2672577393Week 5272577392Week 5272577393Week 5272577394Week 5272577395
NoYes
Oral Semaglutide 7 mg74
Oral Semaglutide 14 mg101
Placebo12
Oral Semaglutide 3 mg126
Oral Semaglutide 7 mg100
Oral Semaglutide 14 mg72
Placebo164
Oral Semaglutide 3 mg50
Oral Semaglutide 7 mg67
Oral Semaglutide 14 mg91
Placebo16
Oral Semaglutide 3 mg123
Oral Semaglutide 7 mg102
Oral Semaglutide 14 mg77
Placebo156

Participants Who Achieve: HbA1c ≤ 6.5% (48 mmol/Mol) (AACE Target) (Yes/no)

Number of participants achieving HbA1c ≤ 6.5% (48 mmol/mol) according to American Association of Clinical Endocrinologists (AACE) target, at week 26 and week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. (NCT03021187)
Timeframe: Week 26, week 52

InterventionParticipants (Count of Participants)
Week 2672577393Week 2672577394Week 2672577395Week 2672577392Week 5272577392Week 5272577394Week 5272577395Week 5272577393
YesNo
Oral Semaglutide 3 mg24
Oral Semaglutide 7 mg45
Oral Semaglutide 14 mg74
Placebo6
Oral Semaglutide 3 mg152
Oral Semaglutide 7 mg129
Oral Semaglutide 14 mg99
Placebo170
Oral Semaglutide 3 mg20
Oral Semaglutide 7 mg33
Oral Semaglutide 14 mg65
Placebo4
Oral Semaglutide 3 mg153
Oral Semaglutide 7 mg136
Oral Semaglutide 14 mg103
Placebo168

Change From Baseline in Body Weight

Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares). (NCT03987919)
Timeframe: Baseline, Week 40

InterventionKilograms (kg) (Least Squares Mean)
5 mg Tirzepatide-7.8
10 mg Tirzepatide-10.3
15 mg Tirzepatide-12.4
1 mg Semaglutide-6.2

Change From Baseline in Fasting Serum Glucose (FSG)

Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares). (NCT03987919)
Timeframe: Baseline, Week 40

Interventionmilligram per Deciliter (mg/dL) (Least Squares Mean)
5 mg Tirzepatide-56.0
10 mg Tirzepatide-61.6
15 mg Tirzepatide-63.4
1 mg Semaglutide-48.6

Change From Baseline in HbA1c (5 mg)

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares). (NCT03987919)
Timeframe: Baseline, Week 40

InterventionPercentage of HbA1c (Least Squares Mean)
5 mg Tirzepatide-2.09
1 mg Semaglutide-1.86

Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Treatment + Time + Treatment*Time (Type III sum of squares). (NCT03987919)
Timeframe: Baseline, Week 40

InterventionPercentage of HbA1c (Least Squares Mean)
10 mg Tirzepatide-2.37
15 mg Tirzepatide-2.46
1 mg Semaglutide-1.86

Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values

The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Postmeal, Midday Premeal, Midday 2-hour Postmeal, Evening Premeal, Evening 2-hour Postmeal and Bedtime. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares). (NCT03987919)
Timeframe: Baseline, Week 40

Interventionmg/dL (Least Squares Mean)
5 mg Tirzepatide-65.4
10 mg Tirzepatide-70.6
15 mg Tirzepatide-74.3
1 mg Semaglutide-61.4

Percentage of Participants Achieving an HbA1c Target Value of <5.7%

Percentage of Participants Achieving an HbA1c Target Value of <5.7%. (NCT03987919)
Timeframe: Week 40

InterventionPercentage of Participants (Number)
5 mg Tirzepatide29.28
10 mg Tirzepatide44.66
15 mg Tirzepatide50.86
1 mg Semaglutide19.74

Percentage of Participants Achieving an HbA1c Target Value of <7%

Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. (NCT03987919)
Timeframe: Week 40

InterventionPercentage of Participants (Number)
5 mg Tirzepatide85.47
10 mg Tirzepatide88.89
15 mg Tirzepatide92.24
1 mg Semaglutide81.13

Percentage of Participants Who Achieved Weight Loss ≥5%

Percentage of Participants who Achieved Weight Loss ≥5%. (NCT03987919)
Timeframe: Week 40

InterventionPercentage of Participants (Number)
5 mg Tirzepatide68.55
10 mg Tirzepatide82.35
15 mg Tirzepatide86.21
1 mg Semaglutide58.44

Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia

The hypoglycemia events were defined by participant reported events with blood glucose <54mg/dL) (<3.0 mmol/L] or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of postbaseline hypoglycemia was estimated by negative binomial model: number of episodes = Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment. (NCT03987919)
Timeframe: Baseline through Safety Follow-Up (Up to Week 44)

InterventionEpisodes/participant/365.25 days (Mean)
5 mg Tirzepatide0.0102
10 mg Tirzepatide0.0046
15 mg Tirzepatide0.0202
1 mg Semaglutide0.0046

Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Total Score

DTSQc, an 8-item questionnaire, assesses relative change in treatment satisfaction perceived frequency of hyperglycemia, and perceived frequency of hypoglycemia from baseline to week 40 or early termination. 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 to 18 where the higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment. The hyperglycemia and hypoglycemia scores range from -3 to 3 where negative scores indicate fewer problems with blood glucose levels and positive scores indicate more problems than before. LS Mean was determined by ANCOVA with Baseline DTSQs + Pooled Country + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment (Type III sum of squares). (NCT03987919)
Timeframe: Baseline, Week 40

,,,
InterventionUnits on a Scale (Least Squares Mean)
HyperglycemiaHypoglycemiaTotal Score
1 mg Semaglutide-1.1-0.715.8
10 mg Tirzepatide-1.4-0.715.6
15 mg Tirzepatide-1.5-0.816.1
5 mg Tirzepatide-1.3-0.715.7

Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24

Absolute change = HbA1c value at Week 24 minus HbA1c value at baseline. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required. (NCT01169779)
Timeframe: Baseline, Week 24

Interventionpercentage of hemoglobin (Least Squares Mean)
Placebo-0.47
Lixisenatide-0.83

Change From Baseline in 2-Hour Postprandial Plasma Glucose (PPG) at Week 24

The 2-hour PPG test measured blood glucose 2 hours after eating a standardized meal. Change was calculated by subtracting Baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest. (NCT01169779)
Timeframe: Baseline, Week 24

Interventionmmol/L (Least Squares Mean)
Placebo-1.33
Lixisenatide-5.61

Change From Baseline in Body Weight at Week 24

Change was calculated by subtracting Baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required. (NCT01169779)
Timeframe: Baseline, Week 24

Interventionkilogram (Least Squares Mean)
Placebo-1.24
Lixisenatide-1.50

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

Change was calculated by subtracting Baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 1 day after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required. (NCT01169779)
Timeframe: Baseline, Week 24

Interventionmmol/L (Least Squares Mean)
Placebo-0.21
Lixisenatide-0.69

Change From Baseline in Glucose Excursion at Week 24

Glucose excursion = 2-hour PPG minus plasma glucose 30 minutes prior to the standardized meal test, before study drug administration. Change was calculated by subtracting Baseline value from Week 24 value. The on-treatment period for this efficacy variable is the time from the first dose of study drug up to the last dosing day of study drug or up to the introduction of rescue therapy, whichever is the earliest. (NCT01169779)
Timeframe: Baseline, Week 24

Interventionmmol/L (Least Squares Mean)
Placebo-0.79
Lixisenatide-4.78

Percentage of Patients Requiring Rescue Therapy During Main 24-Week Period

Routine fasting self-monitored plasma glucose (SMPG) and central laboratory FPG (and HbA1c after week 12) values were used to determine the requirement of rescue medication. If fasting SMPG value exceeded the specified limit for 3 consecutive days, the central laboratory FPG (and HbA1c after week 12) were performed. Threshold values - from baseline to Week 8: fasting SMPG/FPG >250 milligram/deciliter (mg/dL) (13.9 mmol/L), from Week 8 to Week 12: fasting SMPG/FPG >220 mg/dL (12.2 mmol/L), and from Week 12 to Week 24: fasting SMPG/FPG >200 mg/dL (11.1 mmol/L) or HbA1c >8.5%. For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required. (NCT01169779)
Timeframe: Baseline up to Week 24

Interventionpercentage of participants (Number)
Placebo6.7
Lixisenatide3.6

Percentage of Patients With at Least 5% Weight Loss From Baseline at Week 24

The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required. (NCT01169779)
Timeframe: Baseline, Week 24

Interventionpercentage of participants (Number)
Placebo14.7
Lixisenatide19.7

Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than 7% at Week 24

The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required. (NCT01169779)
Timeframe: Week 24

Interventionpercentage of participants (Number)
Placebo38.8
Lixisenatide53.0

Percentage of Patients With Glycosylated Hemoglobin (HbA1c) Level Less Than or Equal to 6.5% at Week 24

The on-treatment period for this efficacy variable is the time from the first dose of study drug up to 3 days after the last dose of study drug or up to the introduction of rescue therapy, whichever is the earliest. For a patient to be included in mITT population, both baseline and at least 1 post baseline on-treatment assessment for at least 1 efficacy variable, were required. (NCT01169779)
Timeframe: Week 24

Interventionpercentage of participants (Number)
Placebo18.1
Lixisenatide32.4

Number of Patients With Symptomatic Hypoglycemia and Severe Symptomatic Hypoglycemia

Symptomatic hypoglycemia was an event with clinical symptoms that were considered to result from a hypoglycemic episode with an accompanying plasma glucose less than 60 mg/dL (3.3 mmol/L) or associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available. Severe symptomatic hypoglycemia was symptomatic hypoglycemia event in which the patient required the assistance of another person and was associated with either a plasma glucose level below 36 mg/dL (2.0 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, if no plasma glucose measurement was available. (NCT01169779)
Timeframe: First dose of study drug up to 3 days after the last dose administration

,
Interventionparticipants (Number)
Symptomatic hypoglycemiaSevere symptomatic hypoglycemia
Lixisenatide110
Placebo50

Change From Baseline in 7-point Self-measured Plasma Glucose Profile

Mean change from baseline in mean of 7-point self-measured plasma glucose at week 26. The 7-point self-measured plasma glucose levels were measured before and after (120 minutes after the start of the meal) the three main meals (breakfast, lunch and dinner), and at bed time. (NCT02008682)
Timeframe: Week 0, week 26

Interventionmmol/L (Mean)
Liraglutide-2.25
Sitagliptin-1.36

Change From Baseline in Fasting Plasma Glucose

Mean change from baseline in fasting plasma glucose (FPG) at Week 26. (NCT02008682)
Timeframe: Week 0, week 26

Interventionmmol/L (Mean)
Liraglutide-2.347
Sitagliptin-1.205

Change From Baseline in Glycosylated Haemoglobin (HbA1c)

Mean change from baseline in glycosylated haemoglobin A1c (HbA1c) at Week 26. (NCT02008682)
Timeframe: Week 0, week 26

InterventionPercent (%) glycosylated haemoglobin (Mean)
Liraglutide-1.666
Sitagliptin-0.969

Number of Confirmed Hypoglycaemic Episodes

confirmed hypoglycaemic episode defined as severe (unable to treat her/himself) or biochemically confirmed by a plasma glucose < 3.1 mmol/L (NCT02008682)
Timeframe: Weeks 0-26

Interventionepisodes (Number)
Liraglutide2
Sitagliptin1

Subjects Who Achieve (Yes/no) HbA1c Below 7.0 % (American Diabetes Association Target)

Calculated as the percentage of subjects achieving treatment target of HbA1c < 7.0% at Week 26 (NCT02008682)
Timeframe: After 26 weeks of treatment

Interventionpercentage of subjects (Number)
Liraglutide76.5
Sitagliptin52.6

Subjects Who Achieve (Yes/no) HbA1c Below or Equal to 6.5 % (American Association of Clinical Endocrinologists Target)

Calculated as the percentage of subjects achieving treatment target of HbA1c <= 6.5% at Week 26 (NCT02008682)
Timeframe: After 26 weeks of treatment

Interventionpercentage of subjects (Number)
Liraglutide61.7
Sitagliptin26.3

Change From Baseline in Body Weight at Week 30

Change in body weight following 30 weeks of therapy (i.e., body weight at Week 30 minus body weight at baseline) (NCT00993187)
Timeframe: Baseline and Week 30

Interventionkg (Least Squares Mean)
Sitagliptin/Metformin-0.83
Glimepiride0.90

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30

Blood glucose was measured on a fasting basis (collected after an 8- to 10-hour fast). FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 30 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 30 minus FPG at baseline). (NCT00993187)
Timeframe: Baseline and Week 30

Interventionmg/dL (Least Squares Mean)
Sitagliptin/Metformin-47.0
Glimepiride-23.5

Change From Baseline in Hemoglobin A1C (HbA1C) at Week 30

HbA1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%). Change in A1C following 30 weeks of therapy (i.e., A1C at Week 30 minus A1C at baseline). (NCT00993187)
Timeframe: Baseline and Week 30

InterventionPercent of total hemoglobin (Least Squares Mean)
Sitagliptin/Metformin-1.5
Glimepiride-0.7

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

An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product. (NCT00993187)
Timeframe: Up to 30 weeks

InterventionParticipants (Number)
Sitagliptin/Metformin8
Glimepiride8

Number of Participants Who Experienced at Least One Adverse Event (AE)

An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product. (NCT00993187)
Timeframe: Up to 32 weeks

InterventionParticipants (Number)
Sitagliptin/Metformin88
Glimepiride101

Percentage of Participants With HbA1C < 7.0% at Week 30

HbA1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%). (NCT00993187)
Timeframe: Week 30

InterventionPercentage of Participants (Number)
Sitagliptin/Metformin81.2
Glimepiride40.1

Percentage of Participants With One or More Episodes of Hypoglycemia

Symptomatic episodes assessed as likely to be due to hypoglycemia were reported by investigators as adverse experiences of hypoglycemia. Adverse experiences of hypoglycemia were based on all reports of hypoglycemia; a concurrent glucose measurement was not required. (NCT00993187)
Timeframe: Up to Week 30

InterventionPercentage of participants (Number)
Sitagliptin/Metformin5.5
Glimepiride20.1

Change in Body Weight

Change from baseline in body weight was analysed after 26 weeks of treatment. Analysis population set: FAS: all randomised subjects receiving at least one dose of any of the trial products. Missing values were imputed using MMRM. (NCT01907854)
Timeframe: From baseline to week 26

Interventionkg (Mean)
Liraglutide-3.32
Sitagliptin-1.80

Change in Fasting Plasma Glucose

Change from baseline in fasting plasma glucose was analysed after 26 weeks of treatment. Missing values were imputed using MMRM. (NCT01907854)
Timeframe: From baseline to week 26

Interventionnmol/L (Mean)
Liraglutide-1.967
Sitagliptin-0.588

Change in HbA1c (Glycosylated Haemoglobin)

Change from baseline in HbA1c was analysed after 26 weeks of treatment. Analysis population set: full analysis set (FAS); all randomised subjects receiving at least one dose of any of the trial products. Missing values were imputed using mixed model for repeated measurements (MMRM). (NCT01907854)
Timeframe: From baseline to week 26

Interventionpercentage of glycosylated haemoglobin (Mean)
Liraglutide-1.146
Sitagliptin-0.529

Number of Treatment Emergent Adverse Events (TEAEs)

A treatment emergent adverse event (TEAE) was defined as an event that had an onset date (or increase in severity) on or after the first day of exposure to randomised treatment and no later than seven days after the last day of randomised treatment. The number of TEAEs was recorded during 26 weeks of treatment plus one week follow-up period. (NCT01907854)
Timeframe: During 26 weeks of treatment plus one week follow-up period.

Interventionnumber of events (Number)
Liraglutide455
Sitagliptin318

Change in Fasting Blood Lipids

Ratio to baseline in fasting blood lipids (total cholesterol, low density lipoprotein [LDL], very low density lipoprotein [VLDL], high density lipoprotein [HDL], triglycerides, and free fatty acids) were analysed after 26 weeks treatment. Missing values were imputed using MMRM. Here we are presenting ratio to baseline data. (NCT01907854)
Timeframe: From baseline to week 26

,
Interventionratio (Mean)
Total cholesterolLDL cholesterolVLDL cholesterolHDL cholesterolTriglyceridesFree Fatty acids
Liraglutide1.0111.0491.0621.0041.0891.086
Sitagliptin1.0451.1211.0750.9971.0991.104

Change in Systolic Blood Pressure and Diastolic Blood Pressure

Change from baseline in systolic and diastolic blood pressure were analysed after 26 weeks of treatment. Missing values were imputed using MMRM. (NCT01907854)
Timeframe: From baseline to week 26

,
InterventionmmHg (Mean)
Systolic Blood PressureDiastolic Blood Pressure
Liraglutide-3.6-0.23
Sitagliptin-2.57-0.81

Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) (American Diabetes Association Target) (y/n)

Number of subjects who achieve HbA1c <7.0% were analysed after 26 weeks of treatment. Missing values were imputed using MMRM. (NCT01907854)
Timeframe: After 26 weeks of treatment

,
Interventionpercentage (%) (Number)
YesNo
Liraglutide50.649.4
Sitagliptin26.973.1

Change in Beta-cell Function

Change in homeostatic model assessment-beta cell (HOMA-B) from baseline to endpoint (Week 26) (outcome measure is presented as the ratio of endpoint HOMA-B divided by baseline HOMA-B). HOMA-B is a measure of pancreatic beta-cell function. (NCT00603239)
Timeframe: baseline and 26 weeks

Interventionratio (Geometric Mean)
Exenatide Twice Daily (BID)1.08
Placebo0.84

Change in Body Weight

Change in body weight from baseline to endpoint (26 weeks) (NCT00603239)
Timeframe: baseline and 26 weeks

Interventionkg (Least Squares Mean)
Exenatide Twice Daily (BID)-1.43
Placebo-0.75

Change in Fasting Serum Glucose (FSG)

Change in FSG from baseline to endpoint (26 weeks) (NCT00603239)
Timeframe: baseline and 26 weeks

Interventionmmol/L (Least Squares Mean)
Exenatide Twice Daily (BID)-0.65
Placebo0.37

Change in Glycosylated Hemoglobin (HbA1c)

Change in HbA1c from baseline to endpoint after 26 weeks of treatment (i.e., HbA1c at endpoint minus HbA1c at baseline) (NCT00603239)
Timeframe: baseline and 26 weeks

InterventionPercentage (Least Squares Mean)
Exenatide Twice Daily (BID)-0.84
Placebo-0.10

Change in Insulin Sensitivity.

Change in homeostatic model assessment-insulin sensitivity (HOMA-S) from baseline to endpoint (26 weeks) (outcome measure is presented as the ratio of endpoint HOMA-S divided by baseline HOMA-S). (NCT00603239)
Timeframe: baseline and 26 weeks

Interventionratio (Least Squares Mean)
Exenatide Twice Daily (BID)1.09
Placebo1.07

Change in Waist Circumference

Change in waist circumference from baseline to endpoint (26 weeks) (NCT00603239)
Timeframe: baseline and 26 weeks

Interventioncm (Mean)
Exenatide Twice Daily (BID)-2.26
Placebo-1.85

Number of Subjects Who Experienced an Episode of Minor Hypoglycemia

Overall number of subjects who experienced an episode of minor hypoglycemia. (NCT00603239)
Timeframe: 26 weeks

InterventionParticipants (Number)
Exenatide Twice Daily (BID)4
Placebo1

Percentage of Patients Achieving HbA1c <= 6.5%

Percentage of ITT patients who had achieved HbA1c <= 6.5% at endpoint (Week 26 or early discontinuation) (NCT00603239)
Timeframe: 26 weeks

Interventionpercentage of participants (Number)
Exenatide Twice Daily (BID)33.6
Placebo13.0

Percentage of Patients Achieving HbA1c <= 7%

Percentage of intent-to-treat (ITT) patients who had HbA1c > 7% at baseline that decreased to <= 7% at endpoint (Week 26 or early discontinuation) (NCT00603239)
Timeframe: 26 weeks

Interventionpercentage of participants (Number)
Exenatide Twice Daily (BID)49.0
Placebo36.5

Change in Euroqol - 5 Domain Quality of Life (EQ-5D) Score

EQ-5D Score - change from baseline to endpoint (26 weeks). EQ-5D is a 5-item questionnaire used to characterize current health states. The tool and accompanying visual analog scale (VAS) assess 5 domains of quality of life, including mobility, self-care, usual activity, pain, and anxiety/depression. Weights are used to score the responses to the 5 domains, with 3 options possible in each domain: extreme problems, some/moderate problems, or no problems. Scores range from 0 to 1, with a score of 1 representing a perfect health state. (NCT00603239)
Timeframe: baseline and 26 weeks

,
Interventionunits on a scale (Least Squares Mean)
Change in Health State ScoreChange in Mobility componentChange in Self Care componentChange Usual Activities componentChange in Pain/Discomfort componentChange in Anxiety/Depression component
Exenatide Twice Daily (BID)0.790.140.080.170.29-0.10
Placebo-2.940.150.030.190.23-0.26

Change in Impact of Weight on Quality of Life (IWQOL)-Lite Score

"IWQOL-Lite analysis of change from baseline to endpoint (26 weeks). IWQOL-Lite is a 31-item questionnaire, assessing the domains of physical function, self-esteem, sexual life, public distress, and work. Response categories for each item range from 1 = never true to 5 = always true." (NCT00603239)
Timeframe: baseline and 26 weeks

,
Interventionunits on a scale (Least Squares Mean)
Change in Total ScoreChange in Physical Function componentChange in Self-Esteem componentChange in Sexual Life componentChange in Public Distress componentChange in Work component
Exenatide Twice Daily (BID)-1.56-3.840.200.12-0.48-0.91
Placebo0.11-1.05-0.545.01-0.280.08

Hepatic Fat

The effect of exenatide and pioglitazone on liver fat content after one year of treatment in patients with type 2 diabetes. (NCT01432405)
Timeframe: one year

Interventionpercent of liver fat (Mean)
Pioglitazone and Exenatide4.7
Pioglitazone6.5

Plasma Adipocytokines

the effect of the intervention on plasma adiponectin levels. (NCT01432405)
Timeframe: one year

Interventionmicrogram per ml (Mean)
Pioglitazone and Exenatide23.2
Pioglitazone15.8

Mean Change From Baseline in Adiponectin at Week 26.

Calculated as an estimate of the mean change from baseline in Adiponectin at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmcg/mL (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg1.69
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg1.51
Sita -> Sita1.35

Mean Change From Baseline in Apolipoprotein B at Week 26

Calculated as an estimate of the change from baseline in apolipoprotein B (ApoB) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventiong/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.06
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.07
Sita -> Sita-0.05

Mean Change From Baseline in Apolipoprotein B at Week 52

Calculated as an estimate of the change from baseline in apolipoprotein B (ApoB) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventiong/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.03
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.03
Sita -> Sita-0.03

Mean Change From Baseline in Beta-cell Function at Week 26

"Calculated as an estimate of the mean change from baseline in beta-cell function at Week 26.~Derived from fasting plasma glucose (FPG) and fasting insulin using the homeostatic model assessment (HOMA) method with the assumption that normal-weight subjects aged under 35 years have a 100% beta-cell function (HOMA-B)." (NCT00700817)
Timeframe: Week 0, Week 26

Interventionpercentage point (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg27.23
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg28.70
Sita -> Sita4.18

Mean Change From Baseline in Beta-cell Function at Week 52

"Calculated as an estimate of the mean change from baseline in beta-cell function at Week 52.~Derived from fasting plasma glucose (FPG) and fasting insulin using the homeostatic model assessment (HOMA) method with the assumption that normal-weight subjects aged under 35 years have a 100% beta-cell function (HOMA-B)." (NCT00700817)
Timeframe: Week 0, Week 52

Interventionpercentage point (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg22.58
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg25.76
Sita -> Sita3.98

Mean Change From Baseline in Body Weight at Week 26

Calculated as an estimate of the mean change from baseline in body weight at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionkg (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-2.86
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-3.38
Sita -> Sita-0.96

Mean Change From Baseline in Body Weight at Week 52

Calculated as an estimate of the mean change from baseline in body weight at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionkg (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-2.78
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-3.68
Sita -> Sita-1.16

Mean Change From Baseline in Diastolic Blood Pressure (DBP) at Week 26

Calculated as an estimate of the mean change from baseline in diastolic blood pressure (DBP) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

InterventionmmHg (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.71
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg0.07
Sita -> Sita-1.78

Mean Change From Baseline in Diastolic Blood Pressure (DBP) at Week 52

Calculated as an estimate of the mean change from baseline in diastolic blood pressure (DBP) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

InterventionmmHg (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.53
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.87
Sita -> Sita-1.47

Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26

Calculated as an estimate of the mean change from baseline in fasting plasma glucose (FPG) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-1.87
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-2.14
Sita -> Sita-0.83

Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52

Calculated as an estimate of the mean change from baseline in fasting plasma glucose (FPG) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-1.71
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-2.04
Sita -> Sita-0.59

Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 78

Calculated as an estimate of the mean change in fasting plasma glucose (FPG) from baseline to Week 78. (NCT00700817)
Timeframe: Week 0, Week 78

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-1.30
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-1.65

Mean Change From Baseline in Free Fatty Acids (FFA) at Week 26

Calculated as an estimate of the change from baseline in free fatty acids (FFA) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.03
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.07
Sita -> Sita-0.05

Mean Change From Baseline in Free Fatty Acids (FFA) at Week 52

Calculated as an estimate of the change from baseline in free fatty acids (FFA) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.07
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.10
Sita -> Sita-0.06

Mean Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) at Week 26

Calculated as an estimate of the mean change from baseline in glycosylated haemoglobin A1c (HbA1c) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

InterventionPercentage point of total HbA1c (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-1.24
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-1.5
Sita -> Sita-0.9

Mean Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) at Week 52

Calculated as an estimate of the mean change from baseline in glycosylated haemoglobin A1c (HbA1c) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

InterventionPercentage point of total HbA1c (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-1.29
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-1.51
Sita -> Sita-0.88

Mean Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) at Week 78

Calculated as an estimate of the mean change from baseline in glycosylated haemoglobin A1c (HbA1c) at Week 78. (NCT00700817)
Timeframe: Week 0, Week 78

InterventionPercentage point of total HbA1c (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.94
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-1.28

Mean Change From Baseline in High-density Lipoprotein-cholesterol (HDL-C) at Week 26

Calculated as an estimate of the mean change from baseline in high-density lipoprotein-cholesterol (HDL-C) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg0.00
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg0.00
Sita -> Sita0.00

Mean Change From Baseline in High-density Lipoprotein-cholesterol (HDL-C) at Week 52

Calculated as an estimate of the mean change from baseline in high-density lipoprotein-cholesterol (HDL-C) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg0.01
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg0.02
Sita -> Sita0.01

Mean Change From Baseline in Highly Sensitive C-reactive Protein (hsCRP) at Week 26

Calculated as an estimate of the mean change from baseline in highly sensitive C-reactive protein (hsCRP) at week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmg/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-1.02
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.99
Sita -> Sita-0.66

Mean Change From Baseline in Interleukin-6 (IL-6) at Week 26.

Calculated as an estimate of the mean change from baseline in interleukin-6 (IL-6) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionpg/mL (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-1.70
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg1.71
Sita -> Sita0.91

Mean Change From Baseline in Low-density Lipoprotein-cholesterol (LDL-C) at Week 26

Calculated as an estimate of the mean change in low-density lipoprotein-cholesterol (LDL-C) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg0.08
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg0.05
Sita -> Sita0.13

Mean Change From Baseline in Low-density Lipoprotein-cholesterol (LDL-C) at Week 52

Calculated as an estimate of the mean change in low-density lipoprotein-cholesterol (LDL-C) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg0.09
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg0.09
Sita -> Sita0.17

Mean Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Week 26.

Calculated as an estimate of the mean change from baseline in N-terminal pro B-type Natriuretic Peptide (NT-proBNP) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionpmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg5.19
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg3.74
Sita -> Sita3.71

Mean Change From Baseline in Overall Treatment Satisfaction (OTS) at Week 26

The Overall Treatment Satisfaction is a sum of 6 items from the Diabetes Treatment Satisfaction Questionnaire, which is a self-assessment of treatment satisfaction. The scale of each sub-item goes from 0 (lowest satisfaction) to 6 (highest satisfaction) and the overall scale of OTS therefore goes from 0 to 36. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionscores on a scale (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg3.51
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg4.35
Sita -> Sita2.96

Mean Change From Baseline in Overall Treatment Satisfaction (OTS) at Week 52

The Overall Treatment Satisfaction is a sum of 6 items from the Diabetes Treatment Satisfaction Questionnaire, which is a self-assessment of treatment satisfaction. The scale of each sub-item goes from 0 (lowest satisfaction) to 6 (highest satisfaction) and the overall scale of OTS therefore goes from 0 to 36. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionscores on a scale (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg3.32
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg4.31
Sita -> Sita2.96

Mean Change From Baseline in Plasminogen Activator Inhibitor-1 (PAI-1) at Week 26.

Calculated as an estimate of the mean change from baseline in plasminogen activator inhibitor-1 (PAI-1) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

InterventionU/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-833
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-561
Sita -> Sita586

Mean Change From Baseline in Pulse at Week 26

Calculated as an estimate of the mean change from baseline in pulse at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionbeats/minute (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg2.32
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg3.94
Sita -> Sita-0.64

Mean Change From Baseline in Pulse at Week 52

Calculated as an estimate of the mean change from baseline in pulse at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

InterventionmmHg (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg1.72
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg3.09
Sita -> Sita0.09

Mean Change From Baseline in Systolic Blood Pressure (SBP) at Week 26

Calculated as an estimate of the mean change from baseline in Systolic Blood Pressure (SBP) at Week 26 (NCT00700817)
Timeframe: Week 0, Week 26

InterventionmmHg (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.55
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.72
Sita -> Sita-0.94

Mean Change From Baseline in Systolic Blood Pressure (SBP) at Week 52

Calculated as an estimate of the mean change from baseline in systolic blood pressure (SBP) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

InterventionmmHg (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.37
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-2.55
Sita -> Sita-1.03

Mean Change From Baseline in Total Cholesterol at Week 26

Calculated as an estimate of the mean change from baseline in total cholesterol at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.03
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.17
Sita -> Sita-0.02

Mean Change From Baseline in Total Cholesterol at Week 52

Calculated as an estimate of the mean change from baseline in total cholesterol at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.01
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.09
Sita -> Sita0.03

Mean Change From Baseline in Triglycerides (TG) at Week 26

Calculated as an estimate of the change from baseline in triglycerides (TG) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.19
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.43
Sita -> Sita-0.40

Mean Change From Baseline in Triglycerides (TG) at Week 52

Calculated as an estimate of the change from baseline in triglycerides (TG) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.10
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.32
Sita -> Sita-0.23

Mean Change From Baseline in Tumour Necrosis Factor Alpha (TNF-alpha) at Week 26.

Calculated as an estimate of the mean change from baseline in Tumour Necrosis Factor Alpha (TNF-alpha) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionpg/mL (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.55
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.74
Sita -> Sita-0.53

Mean Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C) at Week 26

Calculated as an estimate of the change from baseline in very low-density lipoprotein-cholesterol (VLDL-C) at Week 26. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.11
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.20
Sita -> Sita-0.15

Mean Change From Baseline in Very Low-density Lipoprotein-cholesterol (VLDL-C) at Week 52

Calculated as an estimate of the change from baseline in very low-density lipoprotein-cholesterol (VLDL-C) at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionmmol/L (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.11
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.19
Sita -> Sita-0.15

Mean Change From Baseline in Von Willebrand Factor (vWf) at Week 26.

Calculated as an estimate of the mean change from baseline in von Willebrand Factor (vWf) at Week 26. vWf is a blood glycoprotein involved in haemostasis. (NCT00700817)
Timeframe: Week 0, Week 26

Interventionpercentage point (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-1.73
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-4.34
Sita -> Sita-1.8

Mean Change From Baseline in Waist Circumference at Week 26.

Calculated as an estimate of the mean change from baseline in Waist Circumference at Week 26 (NCT00700817)
Timeframe: Week 0, Week 26

Interventioncm (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-2.69
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-2.63
Sita -> Sita-1.12

Mean Change From Baseline in Waist Circumference at Week 52

Calculated as an estimate of the mean change from baseline in Waist Circumference at Week 52. (NCT00700817)
Timeframe: Week 0, Week 52

Interventionparticipants (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-2.36
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-3.02
Sita -> Sita-1.23

Mean Change From Baseline in Waist to Hip Ratio at Week 26.

Calculated as an estimate of the mean change from baseline in Waist to Hip Ratio at Week 26. The measure is assessed as the circumference of the waist divided by the circumference of the hip. (NCT00700817)
Timeframe: Week 0, Week 26

Interventioncm/cm (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.01
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.01
Sita -> Sita-0.00

Mean Change From Baseline in Waist to Hip Ratio at Week 52

Calculated as an estimate of the mean change from baseline in Waist to Hip Ratio at Week 52. The measure is assessed as the circumference of the waist divided by the circumference of the hip. (NCT00700817)
Timeframe: Week 0, Week 52

Interventioncm/cm (Least Squares Mean)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg-0.00
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg-0.01
Sita -> Sita-0.00

Mean Change in Apolipoprotein B From Week 52 to Week 78

Mean change in apolipoprotein B (ApoB) from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionmmol/L (Mean)
Sita -> Sita -> Lira 1.2 mg0.23
Sita -> Sita -> Lira 1.8 mg0.17

Mean Change in Beta-cell Function From Week 52 to Week 78

Mean change in beta-cell function from Week 52 to Week 78. Derived from fasting plasma glucose (FPG) and fasting insulin using the homeostatic model assessment (HOMA) method with the assumption that normal-weight subjects aged under 35 years have a 100% beta-cell function (HOMA-B). (NCT00700817)
Timeframe: Week 52, Week 78

Interventionpercentage point (Mean)
Sita -> Sita -> Lira 1.2 mg13.31
Sita -> Sita -> Lira 1.8 mg23.09

Mean Change in Body Weight From Week 52 to Week 78

Mean change in body weight from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionkg (Mean)
Sita -> Sita -> Lira 1.2 mg-1.64
Sita -> Sita -> Lira 1.8 mg-2.48

Mean Change in Diastolic Blood Pressure (DBP) From Week 52 to Week 78

Mean change in diastolic blood pressure (DBP) from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

InterventionmmHg (Mean)
Sita -> Sita -> Lira 1.2 mg-0.60
Sita -> Sita -> Lira 1.8 mg0.03

Mean Change in Fasting Plasma Glucose (FPG) From Week 52 to Week 78

Mean change in fasting plasma glucose (FPG) Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionmmol/L (Mean)
Sita -> Sita -> Lira 1.2 mg-0.84
Sita -> Sita -> Lira 1.8 mg-1.42

Mean Change in Free Fatty Acids (FFA) From Week 52 to Week 78

Mean change in free fatty acids (FFA) from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionmmol/L (Mean)
Sita -> Sita -> Lira 1.2 mg0.02
Sita -> Sita -> Lira 1.8 mg-0.01

Mean Change in Glycosylated Haemoglobin A1c (HbA1c) From Week 52 to Week 78

Mean Change in Glycosylated Haemoglobin A1c (HbA1c) from Week 52 to Week 78 (NCT00700817)
Timeframe: Week 52, Week 78

InterventionPercentage point of total HbA1c (Mean)
Sita -> Sita -> Lira 1.2 mg-0.24
Sita -> Sita -> Lira 1.8 mg-0.45

Mean Change in High-density Lipoprotein-cholesterol (HDL-C) From Week 52 to Week 78

Mean change in high-density lipoprotein-cholesterol (HDL-C) from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionmmol/L (Mean)
Sita -> Sita -> Lira 1.2 mg0.02
Sita -> Sita -> Lira 1.8 mg-0.01

Mean Change in Low-density Lipoprotein-cholesterol (LDL-C) From Week 52 to Week 78

Mean change in low-density lipoprotein-cholesterol (LDL-C) from week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionmmol/L (Mean)
Sita -> Sita -> Lira 1.2 mg-0.22
Sita -> Sita -> Lira 1.8 mg-0.25

Mean Change in Overall Treatment Satisfaction (OTS) From Week 52 to Week 78

The Overall Treatment Satisfaction is a sum of 6 items from the Diabetes Treatment Satisfaction Questionnaire, which is a self-assessment of treatment satisfaction. The scale of each sub-item goes from 0 (lowest satisfaction) to 6 (highest satisfaction) and the overall scale of OTS therefore goes from 0 to 36. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionscores on a scale (Mean)
Sita -> Sita -> Lira 1.2 mg1.48
Sita -> Sita -> Lira 1.8 mg0.98

Mean Change in Pulse From Week 52 to Week 78

Mean change in pulse from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionbeats/minute (Mean)
Sita -> Sita -> Lira 1.2 mg0.90
Sita -> Sita -> Lira 1.8 mg2.19

Mean Change in Systolic Blood Pressure (SBP) From Week 52 to Week 78

Mean change in systolic blood pressure (SBP) from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

InterventionmmHg (Mean)
Sita -> Sita -> Lira 1.2 mg-2.12
Sita -> Sita -> Lira 1.8 mg0.35

Mean Change in Total Cholesterol From Week 52 to Week 78

Mean change in total cholesterol from Week 52 to Week 78 (NCT00700817)
Timeframe: Week 52, Week 78

Interventionmmol/L (Mean)
Sita -> Sita -> Lira 1.2 mg-0.16
Sita -> Sita -> Lira 1.8 mg-0.24

Mean Change in Triglycerides (TG) From Week 52 to Week 78

Mean change in triglycerides (TG) from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionmmol/L (Mean)
Sita -> Sita -> Lira 1.2 mg-0.20
Sita -> Sita -> Lira 1.8 mg-0.26

Mean Change in Very Low-density Lipoprotein-cholesterol (VLDL-C) at Week 52 to Week 78

Mean change in very low-density lipoprotein-cholesterol (VLDL-C) from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionmmol/L (Mean)
Sita -> Sita -> Lira 1.2 mg0.03
Sita -> Sita -> Lira 1.8 mg0.02

Mean Change in Waist Circumference From Week 52 to Week 78

Mean change in Waist Circumference from Week 52 to Week 78. (NCT00700817)
Timeframe: Week 52, Week 78

Interventionkg (Mean)
Sita -> Sita -> Lira 1.2 mg-1.33
Sita -> Sita -> Lira 1.8 mg-2.05

Mean Change in Waist to Hip Ratio From Week 52 to Week 78

Mean change in Waist to Hip Ratio from Week 52 to Week 78. The measure is assessed as the circumference of the waist divided by the circumference of the hip. (NCT00700817)
Timeframe: Week 52, Week 78

Interventioncm/cm (Mean)
Sita -> Sita -> Lira 1.2 mg-0.01
Sita -> Sita -> Lira 1.8 mg-0.00

Percentage of Subjects Achieving Treatment Target of HbA1c < 7.0% at Week 26

Calculated as the percentage of subjects achieving treatment target of HbA1c < 7.0% at Week 26 (NCT00700817)
Timeframe: Week 0, Week 26

Interventionpercentage of subjects (Number)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg43
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg55
Sita -> Sita22

Percentage of Subjects Achieving Treatment Target of HbA1c < 7.0% at Week 52

Calculated as an estimate of the percentage of subjects achieving treatment target of HbA1c < 7.0% at Week 52 (NCT00700817)
Timeframe: Week 0, Week 52

Interventionpercentage of subjects (Number)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg50
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg63
Sita -> Sita27

Percentage of Subjects Achieving Treatment Target of HbA1c < 7.0% at Week 78

Calculated as an estimate of the percentage of subjects achieving treatment target of HbA1c < 7.0% at Week 78. Based on the extension 2 FAS. (NCT00700817)
Timeframe: Week 0, Week 78

Interventionpercentage of subjects (Number)
Sita -> Sita -> Lira 1.2 mg49
Sita -> Sita -> Lira 1.8 mg50

Percentage of Subjects Achieving Treatment Target of HbA1c < 7.0% at Week 78

Calculated as an estimate of the percentage of subjects achieving treatment target of HbA1c < 7.0% at Week 78. Based on the FAS. (NCT00700817)
Timeframe: Week 0, Week 78

Interventionpercentage of subjects (Number)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg35
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg51

Percentage of Subjects Achieving Treatment Target of HbA1c =< 6.5% at Week 26

Calculated as the percentage of subjects achieving treatment target of HbA1c =< 6.5% at Week 26 (NCT00700817)
Timeframe: Week 0, Week 26

Interventionpercentage of subjects (Number)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg23
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg36
Sita -> Sita12

Percentage of Subjects Achieving Treatment Target of HbA1c =< 6.5% at Week 52

Calculated as an estimate of the percentage of subjects achieving treatment target of HbA1c =< 6.5% at Week 52 (NCT00700817)
Timeframe: Week 0, Week 52

Interventionpercentage of subjects (Number)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg24
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg40
Sita -> Sita17

Percentage of Subjects Achieving Treatment Target of HbA1c =< 6.5% at Week 78

Calculated as an estimate of the percentage of subjects achieving treatment target of HbA1c =< 6.5% at Week 78. Based on the extension 2 FAS. (NCT00700817)
Timeframe: Week 0, Week 78

Interventionpercentage of subjects (Number)
Sita -> Sita -> Lira 1.2 mg29
Sita -> Sita -> Lira 1.8 mg25

Percentage of Subjects Achieving Treatment Target of HbA1c =< 6.5% at Week 78

Calculated as an estimate of the percentage of subjects achieving treatment target of HbA1c =< 6.5% at Week 78. Based on the FAS. (NCT00700817)
Timeframe: Week 0, Week 78

Interventionpercentage of subjects (Number)
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg12
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg27

Hypoglycaamic Episodes, Weeks 52-78

Number of hypoglycaemic episodes from Week 52 to Week 78, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00700817)
Timeframe: Week 52-78

,,,
Interventionepisodes (Number)
MajorMinorSymptoms onlyUnclassified
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg11230
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg05110
Sita -> Sita -> Lira 1.2 mg0310
Sita -> Sita -> Lira 1.8 mg0600

Hypoglycaemic Episodes (Excluding Outlier Subject), Weeks 0-26

Number of hypoglycaemic episodes from Week 0 to Week 26, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00700817)
Timeframe: Weeks 0-26

,,
Interventionepisodes (Number)
MajorMinorSymptoms onlyUnclassified
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg117120
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg016151
Sita -> Sita011100

Hypoglycaemic Episodes (Excluding Outlier Subject), Weeks 0-52

Number of hypoglycaemic episodes from Week 0 to Week 52, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00700817)
Timeframe: Weeks 0-52

,,
Interventionepisodes (Number)
MajorMinorSymptoms onlyUnclassified
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg124140
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg028291
Sita -> Sita025120

Hypoglycaemic Episodes (Excluding Outlier Subject), Weeks 0-78

Number of hypoglycaemic episodes from Week 0 to Week 78, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00700817)
Timeframe: Weeks 0-78

,,
Interventionepisodes (Number)
MajorMinorSymptoms onlyUnclassified
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg236180
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg033401
Sita -> Sita034130

Hypoglyceamic Episodes, Weeks 0-26

Number of hypoglycaemic episodes from Week 0 to Week 26, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00700817)
Timeframe: Weeks 0-26

,,
Interventionepisodes (Number)
MajorMinorSymptoms onlyUnclassified
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg117120
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg037151
Sita -> Sita011100

Hypoglyceamic Episodes, Weeks 0-52

Number of hypoglycaemic episodes from Week 0 to Week 52, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00700817)
Timeframe: Weeks 0-52

,,
Interventionepisodes (Number)
MajorMinorSymptoms onlyUnclassified
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg124140
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg051291
Sita -> Sita025120

Hypoglyceamic Episodes, Weeks 0-78

Number of hypoglycaemic episodes from Week 0 to Week 78, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. (NCT00700817)
Timeframe: Weeks 0-78

,,
Interventionepisodes (Number)
MajorMinorSymptoms onlyUnclassified
Lira 1.2 mg -> Lira 1.2 mg -> Lira 1.2 mg236180
Lira 1.8 mg -> Lira 1.8 mg -> Lira 1.8 mg056401
Sita -> Sita034130

Reviews

12 reviews available for metformin and Nausea

ArticleYear
Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: A systematic review, meta-analysis and meta-regression of randomized controlled trials.
    Frontiers in endocrinology, 2022, Volume: 13

    Topics: Abdominal Pain; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Diarrhea; Humans; Hypoglycem

2022
Pharmacological interventions for prevention of weight gain in people with schizophrenia.
    The Cochrane database of systematic reviews, 2022, 10-03, Volume: 10

    Topics: Antipsychotic Agents; Betahistine; Famotidine; Fluoxetine; Humans; Melatonin; Metformin; Nausea; Niz

2022
Efficacy and safety of polyethylene glycol loxenatide in type 2 diabetic patients: a systematic review and meta-analysis of randomized controlled trials.
    Scientific reports, 2023, 11-03, Volume: 13, Issue:1

    Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Nausea; Randomized Controlled Tri

2023
Glucagon-like peptide-1 receptor agonists or sodium-glucose cotransporter-2 inhibitors as add-on therapy for patients with type 2 diabetes? A systematic review and meta-analysis of surrogate metabolic endpoints.
    Diabetes & metabolism, 2020, Volume: 46, Issue:4

    Topics: Blood Glucose; Diabetes Mellitus, Type 2; Diarrhea; Drug Therapy, Combination; Glucagon-Like Peptide

2020
Once weekly exenatide: efficacy, tolerability and place in therapy.
    Diabetes, obesity & metabolism, 2013, Volume: 15, Issue:10

    Topics: Blood Glucose; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Diarrhea; Drug Administration

2013
Beneficial effect of lixisenatide after 76 weeks of treatment in patients with type 2 diabetes mellitus: A meta-analysis from the GetGoal programme.
    Diabetes, obesity & metabolism, 2017, Volume: 19, Issue:2

    Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Femal

2017
Occurrence of nausea, vomiting and diarrhoea reported as adverse events in clinical trials studying glucagon-like peptide-1 receptor agonists: A systematic analysis of published clinical trials.
    Diabetes, obesity & metabolism, 2017, Volume: 19, Issue:3

    Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 2; Diarrhea; Drug Therapy, Combination; Exenatide;

2017
Metformin vs thiazolidinediones for treatment of clinical, hormonal and metabolic characteristics of polycystic ovary syndrome: a meta-analysis.
    Clinical endocrinology, 2011, Volume: 74, Issue:3

    Topics: Dehydroepiandrosterone Sulfate; Diarrhea; Female; Humans; Hypoglycemic Agents; Metformin; Nausea; Pi

2011
Liraglutide: from clinical trials to clinical practice.
    Diabetes, obesity & metabolism, 2012, Volume: 14 Suppl 2

    Topics: Administration, Oral; Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dose-Respo

2012
Management of diabetes and pancreatic cancer.
    Oncology nursing forum, 2012, Volume: 39, Issue:5

    Topics: Adenocarcinoma; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Thera

2012
Evolution of exenatide as a diabetes therapeutic.
    Current diabetes reviews, 2013, Mar-01, Volume: 9, Issue:2

    Topics: Animals; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; D

2013
[Metformin efficacious in poorly controlled diabetes mellitus type 2].
    Nederlands tijdschrift voor geneeskunde, 2000, Sep-30, Volume: 144, Issue:40

    Topics: Abdominal Pain; Acidosis, Lactic; Aged; Blood Glucose; Contraindications; Diabetes Mellitus; Diabete

2000

Trials

22 trials available for metformin and Nausea

ArticleYear
Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial.
    Diabetes care, 2019, Volume: 42, Issue:12

    Topics: Adult; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Femal

2019
Phase 1 dose-finding study of metformin in combination with concurrent cisplatin and radiotherapy in patients with locally advanced head and neck squamous cell cancer.
    Cancer, 2020, 01-15, Volume: 126, Issue:2

    Topics: Acute Kidney Injury; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy

2020
Feasibility trial of metformin XR in people with pre-diabetes and stroke (MIPPS)-randomised open blinded endpoint controlled trial.
    Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 2021, Volume: 86

    Topics: Adult; Aged; Australia; Delayed-Action Preparations; Feasibility Studies; Female; Headache; Humans;

2021
Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.
    The New England journal of medicine, 2021, 08-05, Volume: 385, Issue:6

    Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Sche

2021
Exenatide twice daily versus insulin glargine for the treatment of type 2 diabetes in Poland - subgroup data from a randomised multinational trial GWAA.
    Endokrynologia Polska, 2013, Volume: 64, Issue:5

    Topics: Administration, Oral; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Sch

2013
Lixisenatide treatment improves glycaemic control in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin with or without sulfonylurea: a randomized, double-blind, placebo-controlled, 24-week trial (GetGoal-M-Asia).
    Diabetes/metabolism research and reviews, 2014, Volume: 30, Issue:8

    Topics: Adult; China; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Resistance; Drug Resistance, Mult

2014
Metformin Addition to Chemotherapy in Stage IV Non-Small Cell Lung Cancer: an Open Label Randomized Controlled Study.
    Asian Pacific journal of cancer prevention : APJCP, 2015, Volume: 16, Issue:15

    Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplat

2015
Polyethylene glycol loxenatide injections added to metformin effectively improve glycemic control and exhibit favorable safety in type 2 diabetic patients.
    Journal of diabetes, 2017, Volume: 9, Issue:2

    Topics: Adult; Asian People; Blood Glucose; China; Diabetes Mellitus, Type 2; Dose-Response Relationship, Dr

2017
Efficacy and safety of liraglutide versus sitagliptin, both in combination with metformin, in Chinese patients with type 2 diabetes: a 26-week, open-label, randomized, active comparator clinical trial.
    Diabetes, obesity & metabolism, 2016, Volume: 18, Issue:8

    Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anorexia; Asian People; Blood Glucose; Body Weight; Chin

2016
Efficacy and safety of sitagliptin/metformin fixed-dose combination compared with glimepiride in patients with type 2 diabetes: A multicenter randomized double-blind study.
    Journal of diabetes, 2017, Volume: 9, Issue:4

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Diarrhea; Double-Blind Method; Drug Th

2017
Efficacy and safety of switching from sitagliptin to liraglutide in subjects with type 2 diabetes (LIRA-SWITCH): a randomized, double-blind, double-dummy, active-controlled 26-week trial.
    Diabetes, obesity & metabolism, 2016, Volume: 18, Issue:12

    Topics: Adult; Aged; Aged, 80 and over; Asia; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Double-

2016
Safety and tolerability of high doses of taspoglutide, a once-weekly human GLP-1 analogue, in diabetic patients treated with metformin: a randomized double-blind placebo-controlled study.
    Diabetic medicine : a journal of the British Diabetic Association, 2010, Volume: 27, Issue:5

    Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Dou

2010
A placebo-controlled trial of exenatide twice-daily added to thiazolidinediones alone or in combination with metformin.
    Diabetes, obesity & metabolism, 2010, Volume: 12, Issue:12

    Topics: Diabetes Mellitus, Type 2; Double-Blind Method; Exenatide; Female; Glycated Hemoglobin; Humans; Hypo

2010
Exenatide decreases hepatic fibroblast growth factor 21 resistance in non-alcoholic fatty liver disease in a mouse model of obesity and in a randomised controlled trial.
    Diabetologia, 2011, Volume: 54, Issue:12

    Topics: Adult; Aged; Animals; Body Weight; Diabetes Mellitus, Type 2; Disease Models, Animal; Drug Therapy,

2011
[Metabolic control and weight loss in patients with obesity and type 2 diabetes mellitus, treated with exenatide].
    Medicina clinica, 2012, Dec-01, Volume: 139, Issue:13

    Topics: Adult; Aged; Anti-Obesity Agents; Antihypertensive Agents; Blood Glucose; Combined Modality Therapy;

2012
Efficacy and safety of switching from the DPP-4 inhibitor sitagliptin to the human GLP-1 analog liraglutide after 52 weeks in metformin-treated patients with type 2 diabetes: a randomized, open-label trial.
    Diabetes care, 2012, Volume: 35, Issue:10

    Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Gl

2012
Efficacy and tolerability of exenatide monotherapy in obese patients with newly diagnosed type 2 diabetes: a randomized, 26 weeks metformin-controlled, parallel-group study.
    Chinese medical journal, 2012, Volume: 125, Issue:15

    Topics: Adult; Diabetes Mellitus, Type 2; Exenatide; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypo

2012
Efficacy and tolerability of taspoglutide versus pioglitazone in subjects with type 2 diabetes uncontrolled with sulphonylurea or sulphonylurea-metformin therapy: a randomized, double-blind study (T-emerge 6).
    Diabetes, obesity & metabolism, 2013, Volume: 15, Issue:3

    Topics: Adolescent; Adult; Blood Glucose; Diabetes Mellitus, Type 2; Dizziness; Double-Blind Method; Drug Ad

2013
Effect of pramlintide on weight in overweight and obese insulin-treated type 2 diabetes patients.
    Obesity research, 2004, Volume: 12, Issue:4

    Topics: Aged; Amyloid; Body Mass Index; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Double-Bl

2004
Efficacy, dose-response relationship and safety of once-daily extended-release metformin (Glucophage XR) in type 2 diabetic patients with inadequate glycaemic control despite prior treatment with diet and exercise: results from two double-blind, placebo-c
    Diabetes, obesity & metabolism, 2005, Volume: 7, Issue:1

    Topics: Adult; Aged; Blood Glucose; Cholesterol, LDL; Delayed-Action Preparations; Diabetes Mellitus, Type 2

2005
The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial.
    Annals of internal medicine, 2007, Apr-03, Volume: 146, Issue:7

    Topics: Adult; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Double-Blind M

2007
Weight-reducing effect of diguanides in obese non-diabetic women.
    British medical journal, 1969, Apr-05, Volume: 2, Issue:5648

    Topics: Adult; Appetite; Bicarbonates; Body Weight; Clinical Trials as Topic; Female; Glucose Tolerance Test

1969

Other Studies

7 other studies available for metformin and Nausea

ArticleYear
Distinguishing characteristics of exposure to biguanide and sulfonylurea anti-diabetic medications in the United States.
    The American journal of emergency medicine, 2022, Volume: 56

    Topics: Abdominal Pain; Acidosis; Adolescent; Adult; Aged; Child; Creatinine; Diabetes Mellitus; Diarrhea; D

2022
Transient Complete Blindness Due to Metformin-Associated Lactic Acidosis (MALA) Reversed with Hemodialysis.
    The American journal of case reports, 2022, Apr-18, Volume: 23

    Topics: Acidosis, Lactic; Acute Kidney Injury; Aged; Blindness; Diabetes Mellitus, Type 2; Diarrhea; Female;

2022
Case 15-2021: A 76-Year-Old Woman with Nausea, Diarrhea, and Acute Kidney Failure.
    The New England journal of medicine, 2021, May-20, Volume: 384, Issue:20

    Topics: Acidosis, Lactic; Acute Kidney Injury; Aged; Coronary Artery Disease; Creatinine; Diabetes Mellitus,

2021
Are we missing hypoglycaemia? Elderly patients with insulin-treated diabetes present to primary care frequently with non-specific symptoms associated with hypoglycaemia.
    Primary care diabetes, 2018, Volume: 12, Issue:2

    Topics: Accidental Falls; Age Factors; Aged; Biomarkers; Blood Glucose; Cross-Sectional Studies; Diabetes Me

2018
Metformin stinks, literally.
    Annals of internal medicine, 2010, Feb-16, Volume: 152, Issue:4

    Topics: Adult; Diabetes Mellitus; Dosage Forms; Drugs, Generic; Humans; Hypoglycemic Agents; Male; Metformin

2010
Summaries for patients. Exenatide therapy for type 2 diabetes.
    Annals of internal medicine, 2007, Apr-03, Volume: 146, Issue:7

    Topics: Adult; Aged; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Exenatide; F

2007
Metformin and fibrinolysis.
    Scandinavian journal of haematology, 1969, Volume: 6, Issue:4

    Topics: Adult; Aged; Blood Glucose; Cholesterol; Female; Fibrinogen; Fibrinolysis; Gastrointestinal Diseases

1969