Positive results have been reported from the sixth and last global phase 3a study (SUSTAIN 6) of semaglutide (Novo Nordisk), an investigational glucagon-like peptide-1 (GLP-1) analogue, which was administered subcutaneously once weekly in the SUSTAIN trials. The new double-blind study investigated the long-term cardiovascular and other safety outcomes of semaglutide (0.5 mg and 1.0 mg) compared with placebo, both administered in addition to standard of care. Approximately 3,300 subjects with type-2 diabetes (T2D) were treated for two years.
The SUSTAIN 6 trial achieved its primary endpoint of demonstrating the noninferiority of semaglutide compared with placebo in terms of major cardiovascular events (MACEs), as well as a statistically significant reduction in cardiovascular risk. The primary endpoint was defined as the composite outcome of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
According to Novo Nordisk, semaglutide can help patients with T2D 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 patients with T2D. The drug is also being developed as an oral tablet for the treatment of T2D and as once-daily subcutaneous formulations for the treatment of T2D and weight management.
Novo Nordisk expects to file once-weekly subcutaneous semaglutide for FDA review as a T2D treatment in the fourth quarter of 2016.
The phase 3 SUSTAIN clinical trial program consisted of six global studies of semaglutide administered subcutaneously once weekly in more than 7,000 subjects with T2D.
- SUSTAIN 1 – a 30-week efficacy and safety trial of semaglutide versus placebo in 388 treatment-naïve subjects with T2D. The results were reported in July 2015.
- SUSTAIN 2 – a 56-week efficacy and safety trial of semaglutide versus sitagliptin once daily as an add-on to metformin and/or a thiazolidinedione in 1,231 subjects with T2D. The results were reported in December 2015.
- SUSTAIN 3 – a 56-week efficacy and safety trial of semaglutide versus 2.0 mg exenatide once weekly as an add-on to one or two oral antidiabetic drugs in 813 subjects with T2D. The results were reported in September 2015.
- SUSTAIN 4 – a 30-week efficacy and safety trial of semaglutide versus insulin glargine once daily as an add-on to metformin with or without sulfonylurea in 1,089 insulin-naïve subjects with T2D. The results were reported in November 2015.
- SUSTAIN 5 – a 30-week efficacy and safety trial of semaglutide versus placebo as an add-on to basal insulin alone or basal insulin in combination with metformin in 397 subjects with T2D. The results were reported in February 2016.
- SUSTAIN 6 – a two-year trial to evaluate cardiovascular and other long-term outcomes with semaglutide in approximately 3,300 subjects with T2D.
Source: Novo Nordisk; April 28, 2016.