Semaglutide - a novel long-acting GLP-1 receptor agonist with proven reduction in cardiovascular events in type 2 diabetes

Semaglutide, a new long-acting Glucagon-like peptide-1 receptor agonist (GLP-1-RA) with once weekly dosing, was developed for the treatment of people with type 2 diabetes. The worldwide phase 3 trial programme included more than 7000 patients in the randomised, controlled SUSTAIN 1 to 6 studies. SUSTAIN 1 to 5 showed mean HbA(1c) reductions between 1.2 and 1.45 % (semaglutide 0.5mg) and 1.5 and 1.8 % (semaglutide 1.0mg), respectively, after 30 or 56 weeks, with significant advantages over placebo, sitagliptin 100mg once daily, exenatide prolonged-release suspension for injection (only semaglutide 1.0mg was investigated) and insulin glargine 100 U/ml (starting dose 10 U once daily). The mean loss of body weight in patients on semaglutide 0.5mg and 1.0mg was 3.5 to 4.3 kg and 4.5 to 6.4 kg, respectively. The cardiovascular outcome study SUSTAIN 6 resulted in a relative risk reduction regarding the primary combined cardiovascular endpoint by 26 % of 8.9 % to 6.6 % (p = 0.02 for superiority) after a 2-year treatment with semaglutide 0.5mg or 1.0mg compared with placebo - each treatment in the context of the "standard of care". Moreover, compared with the placebo group, patients on semaglutide showed less renal events (3.8 % vs. 6.1 %; p = 0.005), but more retinopathy complications (3.0 % vs. 1.8 %; p = 0.02), stronger HbA(1c) reductions after 104 weeks by 0.66 % points and 1.05 % points for 0.5 and 1.0mg, respectively (p < 0.0001 for both), and a stronger weight reduction by 2.9 kg (0.5 mg) and 4.4 kg (1.0 mg) (p < 0.0001 for both). As with other GLP-1-RAs, semaglutide is associated with reductions of systolic blood pressure, increased heart rate, increased gastrointestinal side effects and a relatively low risk of hypoglycemia considering the marked HbA(1c) reduction. In summary, the strengths of semaglutide are a substantial HbA(1c) reduction, the pronounced weight loss and beneficial cardiovascular endpoint data.