Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine in insulin-naïve subjects with type 2 diabetes (SUSTAIN 4)

Aroda, Vanita R.; Bain, Stephen C.; Cariou, Bertrand; Piletič, Milivoj; Rose, Ludger; Bergan, Eirik Quamme; Zacho, Jeppe; DeVries, J. Hans

doi:10.1016/s0168-8227(16)31024-5

Cited by 5 publications

(14 citation statements)

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“…Semaglutide was generally well tolerated and reported side effects were consistent with other semaglutide trials . No unexpected treatment‐related safety issues were identified.…”

Section: Discussionsupporting

confidence: 70%

“…This interpretation is supported by similar GIRs in the two arms and the similar rates of glucose recovery. Furthermore, in the studies of semaglutide conducted to date, no increases in rates of hypoglycaemia have been noted, although these (and indeed the present study) were not powered to evaluate differences in severe hypoglycaemia; [14][15][16]34 however, in the LEADER trial with the closely-related molecule, liraglutide, a statistically significantly lower incidence of severe hypoglycaemia was seen for liraglutide compared with placebo. 35 In summary, the clinical relevance of the observations in the present trial remains uncertain.…”

Section: Discussionmentioning

confidence: 71%

“…NS, not significant No safety findings were identified based on clinical laboratory assessments (including amylase, lipase and calcitonin), physical examination or ECG, and no participant developed anti-semaglutide antibodies. A greater mean (SD) reduction in systolic BP from baseline to end-of-treatment was observed for participants treated with semaglutide vs placebo (−8 [16] vs −3 [12] mm Hg); diastolic BP was the same with both treatments (−2 [10] mm Hg). The mean heart rate increased with semaglutide and was unchanged with placebo (6 [8] vs 0 [8] beats/min).…”

Section: Safetymentioning

confidence: 94%

“…With 94% homology to native GLP‐1, semaglutide has three structural modifications that prolong its half‐life to ~1 week, making it appropriate for once‐weekly administration . In phase III trials, semaglutide led to improved glycaemic control and decreased body weight, with a safety profile similar to other GLP‐1 receptor agonists (GLP‐1RAs) . Liraglutide, having a similar structure to semaglutide but a different pharmacokinetic profile, was found to have no effect on the counterregulatory responses to hypoglycaemia .…”

Section: Introductionmentioning

confidence: 99%

“…3,12 In phase III trials, semaglutide led to improved glycaemic control and decreased body weight, with a safety profile similar to other GLP-1 receptor agonists (GLP-1RAs). [14][15][16] Liraglutide, having a similar structure to semaglutide but a different pharmacokinetic profile, was found to have no effect on the counterregulatory responses to hypoglycaemia. [17][18][19] These responses have not been evaluated in people treated with semaglutide.…”

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confidence: 99%

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Effect of once‐weekly semaglutide on the counterregulatory response to hypoglycaemia in people with type 2 diabetes: A randomized, placebo‐controlled, double‐blind, crossover trial

Korsatko

Jensen

Brunner

et al. 2018

Diabetes Obesity Metabolism

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AimsTo investigate the effects of semaglutide vs placebo on glucagon and other counterregulatory hormones during hypoglycaemia in type 2 diabetes (T2D).MethodsIn this double‐blind, placebo‐controlled, single‐centre trial, we randomized 38 men and women (treated only with metformin) 1:1 to 2 12‐week crossover periods of once‐weekly subcutaneous semaglutide or placebo, each followed by a hypoglycaemic clamp procedure. The primary endpoint was change in glucagon concentration from target plasma glucose (PG) level 5.5 mmol/L to nadir (target 2.5 mmol/L).ResultsThe mean (range) participant age was 54.2 (41‐64) years, body mass index 29.4 (23.3‐36.1) kg/m2, glycated haemoglobin 60.8 (44.3‐83.6) mmol/mol (7.7 [6.2‐9.8]%), and diabetes duration 4.5 (0.3‐13.2) years. A total of 35 participants completed the trial and were included in the analyses. During the hypoglycaemic clamp from 5.5 mmol/L PG to nadir, the absolute change in mean glucagon concentration was similar for semaglutide vs placebo: 88.3 vs 83.1 pg/mL (estimated difference 5.2 pg/mL [95% confidence interval −7.7 to 18.1]). Concentrations of other counterregulatory hormones increased with both treatments, with a statistically significantly lower increase for noradrenaline and cortisol with semaglutide vs placebo. The glucose infusion rate to maintain constant clamp levels was similar for each treatment group, suggesting an overall similar counterregulatory response. The mean hypoglycaemic symptom score and proportion of participants recognizing hypoglycaemia during the study were lower for semaglutide vs placebo treatment at nadir, but cognitive function test results were similar. No new safety issues were observed for semaglutide.ConclusionsSemaglutide treatment did not compromise the counterregulatory glucagon response during experimental hypoglycaemia in people with T2D.

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“…Semaglutide was generally well tolerated and reported side effects were consistent with other semaglutide trials . No unexpected treatment‐related safety issues were identified.…”

Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 71%

Section: Safetymentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Effect of once‐weekly semaglutide on the counterregulatory response to hypoglycaemia in people with type 2 diabetes: A randomized, placebo‐controlled, double‐blind, crossover trial

Korsatko

Jensen

Brunner

et al. 2018

Diabetes Obesity Metabolism

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Efficacy and Safety of GLP-1 Receptor Agonists Across the Spectrum of Type 2 Diabetes Mellitus

Leiter

Nauck

2017

Exp Clin Endocrinol Diabetes

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For patients with type 2 diabetes mellitus, glucagon-like peptide-1 receptor agonists (GLP-1RAs) generally exert robust glucose-lowering effects that are at least as effective as insulin. As monotherapies, changes from baseline in HbA with GLP-1RAs ranged from -1.9 to -0.7% in phase 3 trials. In addition, GLP-1RAs confer a low risk of hypoglycaemia and have a body-weight advantage (changes from baseline ranging from -4.0 to -0.4 kg). There is also evidence of significant reductions in risk for cardiovascular events with some of these agents, with a number of other trials underway. Gastrointestinal adverse events typically increase with GLP-1RAs, although these are generally mild to moderate in intensity and rarely require treatment discontinuation. The GLP-1RAs that are commercially available or in development vary in structure and pharmacokinetics. These differences affect the frequency of administration and can also affect their relative efficacy and safety. This review summarizes the findings of phase 3 glycaemic control trials of available GLP-1RAs and considers them in the context of the distinct clinical needs of individual patients.

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Subcutaneous semaglutide (NN9535) for the treatment of type 2 diabetes

Hedrington

Tsiskarishvili

2018

Expert Opinion on Biological Therapy

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It is critical for individuals with type 2 diabetes mellitus (T2DM) to maintain optimal glycemia while avoiding hypoglycemia, control body weight, and reduce cardiovascular risk. The GLP-1 receptor agonists stimulate glucose-dependent insulin release (low risk of hypoglycemia), inhibit glucagon secretion, slow gastric emptying and suppress appetite (weight loss). The new members of the class are available as once daily or weekly injections. Additionally, some members of the class have demonstrated reduced cardiovascular risk. Areas covered: This manuscript describes semaglutide - a new investigational long acting GLP-1 receptor agonist. The key trials from the clinical development process are reviewed and important end-points highlighted. Expert opinion: Once-weekly semaglutide has shown superiority in reducing glycosylated hemoglobin and body weight in comparison with placebo and active comparators when used as monotherapy or in combination treatment. In addition, semaglutide improved markers of β-cell function and have shown cardiovascular risk reduction similar to once daily liraglutide. Although, overall semaglutide safety was comparable to other GLP-1 receptor agonists (low risk of hypoglycemia and high frequency of gastrointestinal side effects), increase in retinopathy complications requires further investigation.

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Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine in insulin-naïve subjects with type 2 diabetes (SUSTAIN 4)

Cited by 5 publications

References 0 publications

Effect of once‐weekly semaglutide on the counterregulatory response to hypoglycaemia in people with type 2 diabetes: A randomized, placebo‐controlled, double‐blind, crossover trial

Effect of once‐weekly semaglutide on the counterregulatory response to hypoglycaemia in people with type 2 diabetes: A randomized, placebo‐controlled, double‐blind, crossover trial

Efficacy and Safety of GLP-1 Receptor Agonists Across the Spectrum of Type 2 Diabetes Mellitus

Subcutaneous semaglutide (NN9535) for the treatment of type 2 diabetes

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