This is the fourth drug to treat diabetes that also can reduce the risk of heart disease.
Novo Nordisk announced the top-line results from the sixth and last global phase 3a trial, SUSTAIN 6, for semaglutide, a new GLP-1 analogue, which is administered subcutaneously once weekly in the SUSTAIN trials. This double-blinded trial investigated the long-term cardiovascular and other safety outcomes of 0.5 mg and 1.0 mg semaglutide compared with placebo, both in addition to standard-of-care. In the trial, approximately 3,300 people with type 2 diabetes were treated for 104 weeks.
The trial achieved its primary endpoint of showing non-inferiority of major cardiovascular events (MACE) with semaglutide compared with placebo, as well as a statistically significant reduction in cardiovascular risk with semaglutide. In the trial, around 250 MACE were accrued. The primary endpoint of the study was defined as the composite outcome of the first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke.
The safety profile of semaglutide in SUSTAIN 6 was as expected and consistent with previous semaglutide clinical studies.
Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk in a statement added that, “We are very encouraged by the potential for reduction of CV risk in people with type 2 diabetes with semaglutide based on the results of SUSTAIN 6….In addition to the strong efficacy profile, we have also established the safety profile for semaglutide by concluding the six SUSTAIN trials…. With the strong results from SUSTAIN 6, we look forward to the regulatory filing of semaglutide.”
Semaglutide is a new glucagon-like peptide-1 (GLP-1) analogue that can help people with type 2 diabetes achieve substantial improvement of blood glucose with a low risk of hypoglycemia. In addition, semaglutide induces weight loss by decreasing appetite and food intake. Semaglutide administered subcutaneously once weekly is in phase 3 development for the treatment of type 2 diabetes. Furthermore, semaglutide is currently being developed in an oral tablet version for treatment of type 2 diabetes as well as in once-daily subcutaneous versions for treatment of type 2 diabetes and weight management.
The last trial was the SUSTAIN 6 program, which was a phase 3 clinical program comprising six global trials of semaglutide administered subcutaneously once weekly encompassing more than 7,000 people with type 2 diabetes. It was a 2-year trial to evaluate cardiovascular and other long-term outcomes with semaglutide in approximately 3,300 people with type 2 diabetes.
Liraglutide is now the fourth glucose-lowering agent to show cardiovascular benefit and the first of the GLP-1 class.
The first glucose-lowering drug to show a cardiovascular benefit was Cycloset (bromocriptine), then the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin. And pioglitazone, also available generically now, demonstrated cardiovascular benefit over a decade ago.
Novo Nordisk says it expects to file the once-weekly subcutaneous form of semaglutide for regulatory review in the United States and European Union in the fourth quarter of 2016.
- The trial showed success for the primary endpoint of noninferiority for cardiovascular death, myocardial infarction, and stroke compared with placebo and a statistically significant reduction on that combined endpoint as well.
- In total, Novo is conducting six phase III SUSTAIN trials with once-weekly semaglutide, with more than 7,000 participants.
- The drug is also being studied in a once-daily subcutaneous dose for managing type 2 diabetes and weight, and in an oral tablet form for type 2 diabetes.
“Semaglutide significantly reduces the risk of major adverse cardiovascular events in the SUSTAIN 6 trial,” Novo Nordisk media release, April 28, 2016.