The SUSTAIN-6 trial’s results were presented as the last EASD meeting (12nd to 16th September 2016) in Munich), by Steven P. Marso.
SUSTAIN-6 is a pre-regulatory approval cardiovascular outcomes trial for semaglutide, an investigational once-weekly glucagon-like peptide-1 (GLP-1) analogue. The study demonstrated not only overall cardiovascular safety, but also a significant 26% risk reduction in the primary endpoint of cardiovascular death, non-fatal myocardial infarction (heart attack) or non-fatal stroke associated with the use of semaglutide vs placebo, when added to standard of care. The trial randomised 3,297 adults with type 2 diabetes at high cardiovascular risk who were treated for 104 weeks. There was a significant 39% reduction in non-fatal stroke, a 26% non-significant reduction in non-fatal heart attack and a neutral outcome with regard to CV death.
Furthermore, the cardiovascular benefit seen with semaglutide was accompanied by sustained glycaemic control and weight loss. During the trial, more patients treated with placebo intensified their antihyperglycemic treatment compared with semaglutide; however, the difference in glycated haemoglobin levels between semaglutide and placebo-treated patients remained after 2 years. From an overall mean baseline of 8.7%, semaglutide 0.5 mg and 1.0 mg significantly reduced HbA1c by -1.1% and -1.4% vs -0.4% for placebo (both placebo 0.5 mg and 1.0 mg). The observed weight loss with semaglutide 0.5 mg and 1.0 mg treatment was -3.6 kg and -4.9 kg vs placebo (-0.7 kg and -0.5 kg for placebo 0.5 mg and 1.0 mg, respectively).
Fewer serious adverse events were seen with semaglutide vs placebo; however, treatment discontinuation due to adverse events was more frequent with semaglutide, mainly due to gastrointestinal events. In terms of microvascular complications, significantly fewer people treated with semaglutide (62 [3.8%]) vs placebo (100 [6.1%]) had new onset or worsening nephropathy while significantly more people treated with semaglutide (50 [3.0%]) vs placebo (29 [1.8%]) experienced diabetic retinopathy complications.
As cardiovascular disease remains the leading cause of death in type 2 diabetes, the cardiovascular benefits of semaglutide are of potential great clinical benefit.
The scientific session has focused on the cardiovascular outcomes from SUSTAIN 6, with background on the trial design and further findings on key efficacy and safety measures.