Semaglutide: Review and Place in Therapy for Adults With Type 2 Diabetes

Guidelines increasingly highlight the importance of multifactorial management in type 2 diabetes, in contrast to the more traditional focus on glycemic control. Semaglutide, a recently approved glucagon-like peptide-1 receptor agonist, is indicated in Canada for adults with type 2 diabetes to improve glycemic control as monotherapy with diet and exercise when metformin is inappropriate or as an add-on to either metformin alone or metformin plus a sulfonylurea or basal insulin. The Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) clinical trial program for semaglutide comprises 6 pivotal global phase 3a trials (SUSTAIN 1 through 6) and 2 Japanese phase 3a trials. Phase 3b trials include SUSTAIN 7, and SUSTAIN 8 and 9 (both ongoing). Results from the completed trials support the superiority of semaglutide for reduction of glycated hemoglobin levels and weight loss vs. placebo as well as active comparators, including sitagliptin, exenatide extended-release, dulaglutide and insulin glargine. SUSTAIN 6 trial data confirmed cardiovascular safety and demonstrated significant reductions in major cardiovascular events with semaglutide vs. placebo, an outcome that confirmed the noninferiority of semaglutide. The robust and sustained effects of semaglutide on glycated hemoglobin levels and weight loss vs. comparators, as well as its safety and possible cardiovascular benefit, address an unmet need in the treatment of type 2 diabetes. This article overviews data from across the semaglutide clinical trial program, including efficacy and safety results and findings from post hoc analyses. The potential place of semaglutide in clinical practice is discussed.