Novo Nordisk revealed that semaglutide, an investigational glucagon-like peptide-1 (GLP-1) analogue significantly reduced the risk of the primary composite endpoint of time to first occurrence of either cardiovascular (CV) death, non-fatal myocardial infarction (heart attack) or non-fatal stroke by 26% vs placebo, when added to standard of care in 3,297 adults with type 2 diabetes at high CV risk.
Furthermore, there was a significant 39% decrease in non-fatal stroke and a non-significant 26% decrease in non-fatal myocardial infarction and a neutral outcome (2% decrease) in CV death after only two years of treatment.
In this trial, 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 both placebo 0.5 mg and 1.0 mg at 104 weeks, when added to standard of care.
Weight loss benefit
In addition, from a mean baseline of 92.1 kg, adults treated with semaglutide 0.5 mg and 1.0 mg experienced superior and sustained weight loss of -3.6 kg and -4.9 kg, vs -0.7 kg for placebo 0.5 mg and -0.5 kg for placebo 1.0 mg.
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.
The incidence of pancreatitis was lower with semaglutide vs placebo. 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.
“The reduction in cardiovascular events observed with semaglutide in SUSTAIN 6 is notable given the small study population and the short trial duration,” said Dr Steven Marso, SUSTAIN 6 investigator. “These findings are clinically relevant, as cardiovascular disease is the leading cause of death in people with type 2 diabetes and new treatment options that can also reduce the risk of cardiovascular events are needed.”
About the drug
Semaglutide is an analogue of human glucagon-like peptide-1 (GLP-1) that stimulates insulin and suppresses glucagon secretion in a glucose-dependent manner, while decreasing appetite and food intake. With SUSTAIN 6, semaglutide, administered subcutaneously once-weekly, has completed six phase 3a clinical trials for the treatment of adults with type 2 diabetes.
About the trial
SUSTAIN 6 was a multicentre, international, randomised, double-blind, placebo-controlled pre-marketing CV outcomes trial (CVOT) investigating the long-term effects of the drug (0.5 mg and 1.0 mg), compared to placebo, when added to standard of care, in adults with type 2 diabetes at high risk of CV events. The trial was initiated in February 2013 and randomised 3,297 adults with type 2 diabetes from 20 countries that were treated for 104 weeks.