07 Jun Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes SUSTAIN-6 trial
Marso S.P. et al., NEJM 2016
In order to fulfil regulatory requirement of establishing cardiovascular safety of new diabetes therapies in patients with type 2 diabetes a non inferiority trial as compared to placebo was planned for semaglutide (a glucagon-like peptide 1 analogue with an extended half-life of approximately 1 week) to evaluate its cardiovascular and other long term effects. 3297 patients with type 2 diabetes who were on a standard-care regimen were randomized to receive once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks. All participants had either established cardiovascular disease or additional cardiovascular risk factors.
The primary composite outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The primary outcome occurred in 108 of 1648 patients (6.6%) in the semaglutide group and in 146 of 1649 patients (8.9%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.58 to 0.95; P<0.001). Nonfatal myocardial infarction occurred in 2.9% of the patients receiving semaglutide and in 3.9% of those receiving placebo (hazard ratio, 0.74; 95% CI, 0.51 to 1.08; P=0.12); nonfatal stroke occurred in 1.6% and 2.7%, respectively (hazard ratio, 0.61; 95% CI, 0.38 to 0.99; P=0.04). The mean glycated hemoglobin reduced to -1.1% and -1.4% for patients receiving 0.5 mg and1.0mg of semaglutide respectively, compared with 0.4% in the placebo group. Mean weight loss in the semaglutide group was 3.6 kg and 4.9 kg, respectively, compared with about 0.5 kg in the placebo group. Mortality rates from cardiovascular causes were similar in the two groups. New or worsening nephropathy was less common and diabetic retinopathy complications and gastrointestinal disorders were more common in the semaglutide group than in the placebo group. The trial achieved its primary end- point of showing noninferiority in safety of semaglutide compared with placebo in patients with type 2 diabetes at high cardiovascular risk. (Funded by Novo Nordisk; SUSTAIN-6 ClinicalTrials.gov number, NCT01720446.)