Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial

Åhrén, Bo; Masmiquel, Luis; Kumar, Harish; Sargın, Mehmet; Karsbøl, Julie Derving; Jacobsen, Sanja Hald; Chow, Francis C. C.

doi:10.1016/s2213-8587(17)30092-x

Cited by 353 publications

(582 citation statements)

References 31 publications

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“…The most common AEs leading to discontinuation of semaglutide were GI in nature and, overall, most cases of GI AEs were mild or moderate and of a short duration 12, 13, 14, 15, 16, 23, 24. GI AEs are commonly observed across the GLP‐1RA class,2, 9 and may affect treatment outcomes in the real‐world setting.…”

Section: Discussionmentioning

confidence: 99%

“…Key prespecified endpoints were similar across the SUSTAIN 1 to 5 trials 12, 13, 14, 15, 16. For all trials, the primary endpoint was change in HbA1c from baseline to end of treatment (30 or 56 weeks); the confirmatory secondary endpoint was change in body weight from baseline to end of treatment (30 or 56 weeks).…”

Section: Methodsmentioning

confidence: 96%

“…The main between‐trial differences related to pre‐existing treatments, if any, at screening 12, 13, 14, 15, 16…”

Section: Methodsmentioning

confidence: 99%

“…SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) is a global phase III clinical trial programme, designed to evaluate the efficacy and safety of once‐weekly s.c. semaglutide across a range of people with T2D, from those who are drug‐naïve to those receiving OADs and/or insulin 12, 13, 14, 15, 16, 17…”

Section: Introductionmentioning

confidence: 99%

“…In the SUSTAIN 6 trial, semaglutide also showed a 26% cardiovascular risk reduction vs placebo in participants with T2D, as measured by the composite endpoint of cardiovascular death, non‐fatal myocardial infarction or non‐fatal stroke 17. The most common AEs experienced with semaglutide across the SUSTAIN programme were GI in nature 12, 13, 14, 15, 16, 17. The SUSTAIN 7 trial evaluated once‐weekly semaglutide vs once‐weekly dulaglutide in people with T2D18; however, data from SUSTAIN 7 were not available at the time of this analysis.…”

Section: Introductionmentioning

confidence: 99%

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Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme

DeVries

Desouza

Bellary

et al. 2018

Diabetes Obesity Metabolism

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AimTo evaluate the potential for semaglutide to help people with type 2 diabetes (T2D) achieve glycated haemoglobin (HbA1c) targets while avoiding unwanted outcomes, such as weight gain, hypoglycaemia and gastrointestinal (GI) side effects.Materials and methodsData from the phase IIIa SUSTAIN 1 to 5 clinical trials were analysed. Participants had inadequately controlled T2D and were drug‐naïve (SUSTAIN 1) or on a range of background treatments (SUSTAIN 2 to 5). The main protocol‐specified composite endpoint was the proportion of participants achieving HbA1c <53 mmol/mol (7.0%) at end of treatment (30 or 56 weeks) without weight gain and with no severe or blood glucose (BG)‐confirmed symptomatic hypoglycaemia. A post hoc composite endpoint was the proportion of participants achieving the primary composite endpoint without moderate or severe GI adverse events (AEs).ResultsAcross the SUSTAIN trials 1 to 5, 3918 participants with T2D were randomized to once‐weekly subcutaneous semaglutide 0.5 mg, 1.0 mg, or comparators (placebo, sitagliptin 100 mg, exenatide extended release 2.0 mg or insulin glargine). The proportion of participants achieving HbA1c <53 mmol/mol (7.0%) with no weight gain and no severe/BG‐confirmed symptomatic hypoglycaemia was 47% to 66% (semaglutide 0.5 mg) and 57% to 74% (semaglutide 1.0 mg) vs 7% to 19% (placebo) and 16% to 29% (active comparators; all P < .0001). More participants achieved the primary composite endpoint with no moderate or severe GI AEs with semaglutide vs comparators (all P < .0001).ConclusionSemaglutide helped more people with T2D achieve HbA1c targets than did comparators in the SUSTAIN 1 to 5 trials, while avoiding unwanted outcomes such as weight gain, hypoglycaemia and GI side effects.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 96%

“…The main between‐trial differences related to pre‐existing treatments, if any, at screening 12, 13, 14, 15, 16…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme

DeVries

Desouza

Bellary

et al. 2018

Diabetes Obesity Metabolism

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Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea

Rosenstock

Allison

Birkenfeld

et al. 2019

JAMA

295

399

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Phase 3 trials have not compared oral semaglutide, a glucagon-like peptide 1 receptor agonist, with other classes of glucose-lowering therapy. OBJECTIVE To compare efficacy and assess long-term adverse event profiles of once-daily oral semaglutide vs sitagliptin, 100 mg added on to metformin with or without sulfonylurea, in patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, double-dummy, parallel-group, phase 3a trial conducted at 206 sites in 14 countries over 78 weeks from February 2016 to March 2018. Of 2463 patients screened, 1864 adults with type 2 diabetes uncontrolled with metformin with or without sulfonylurea were randomized. INTERVENTIONS Patients were randomized to receive once-daily oral semaglutide, 3 mg (n = 466), 7 mg (n = 466), or 14 mg (n = 465), or sitagliptin, 100 mg (n = 467). Semaglutide was initiated at 3 mg/d and escalated every 4 weeks, first to 7 mg/d then to 14 mg/d, until the randomized dosage was achieved. MAIN OUTCOMES AND MEASURES The primary end point was change in glycated hemoglobin (HbA 1c), and the key secondary end point was change in body weight, both from baseline to week 26. Both were assessed at weeks 52 and 78 as additional secondary end points. End points were tested for noninferiority with respect to HbA 1c (noninferiority margin, 0.3%) prior to testing for superiority of HbA 1c and body weight. RESULTS Among 1864 patients randomized (mean age, 58 [SD, 10] years; mean baseline HbA 1c , 8.3% [SD, 0.9%]; mean body mass index, 32.5 [SD, 6.4]; n=879 [47.2%] women), 1758 (94.3%) completed the trial and 298 prematurely discontinued treatment (16.7% for semaglutide, 3 mg/d; 15.0% for semaglutide, 7 mg/d; 19.1% for semaglutide, 14 mg/d; and 13.1% for sitagliptin). Semaglutide, 7 and 14 mg/d, compared with sitagliptin, significantly reduced HbA 1c (differences,-0.3% [95% CI,-0.4% to-0.1%] and-0.5% [95% CI,-0.6% to-0.4%], respectively; P < .001 for both) and body weight (differences,-1.6 kg [95% CI,-2.0 to-1.1 kg] and-2.5 kg [95% CI,-3.0 to-2.0 kg], respectively; P < .001 for both) from baseline to week 26. Noninferiority of semaglutide, 3 mg/d, with respect to HbA 1c was not demonstrated. Week 78 reductions in both end points were statistically significantly greater with semaglutide, 14 mg/d, vs sitagliptin. CONCLUSIONS AND RELEVANCE Among adults with type 2 diabetes uncontrolled with metformin with or without sulfonylurea, oral semaglutide, 7 mg/d and 14 mg/d, compared with sitagliptin, resulted in significantly greater reductions in HbA 1c over 26 weeks, but there was no significant benefit with the 3-mg/d dosage. Further research is needed to assess effectiveness in a clinical setting.

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Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity

Wadden

Bailey

Billings

et al. 2021

JAMA

569

605

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Key PointsQuestionIn adults with overweight or obesity without diabetes, what effect does once-weekly subcutaneous semaglutide, 2.4 mg, have on body weight when added to intensive behavioral therapy with an initial low-calorie diet?FindingsIn this randomized clinical trial that included 611 adults with overweight or obesity, 68 weeks’ treatment with once-weekly subcutaneous semaglutide vs placebo, combined with intensive behavioral therapy (and a low-calorie diet for the initial 8 weeks), resulted in reductions in body weight of 16.0% vs 5.7%, respectively; the difference was statistically significant.MeaningWhen used as an adjunct to intensive behavioral therapy and initial low-calorie diet, once-weekly subcutaneous semaglutide produced significantly greater weight loss than placebo during 68 weeks in adults with overweight or obesity.

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Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial

Cited by 353 publications

References 31 publications

Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme

Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme

Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea

Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity

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