Semaglutide as an Antidiabetic Medication: A Summary of the Evidence from the Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes Clinical Trial Program

Background: The Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) clinical trial program was a phase III, multinational, multicenter program comprising 13 trials. Objective: Investigate the safety and efficacy of once-weekly, subcutaneous semaglutide versus other antidiabetic comparators, both as a monotherapy and in addition to other antidiabetic medications. Methods: This review summarizes the 10 trials that comprise the bulk of the evidence which led to FDA approval of semaglutide as an antidiabetic drug. Most articles were accessed via the National Center for Biotechnology Information database using pertinent search terms. Results: Semaglutide 0.5 mg and 1 mg weekly subcutaneous injection led to HA1c reductions by 1.1%–1.5% and 1.5%–1.8%, respectively. Bodyweight reduction with 0.5 mg and 1 mg dose of semaglutide ranged from 3.47–4.6 kg and 4.53–6.5 kg, respectively. SUSTAIN 6, in particular, found cardiovascular risk factor benefits, including the rate of nonfatal myocardial infarction, cardiovascular death and nonfatal strokes in high-risk patients correlated with the use of semaglutide in patients with type 2 diabetes. Conclusions: Semaglutide is superior to other glucagon-like peptide-1 receptor agonists, including exenatide, dulaglutide, and liraglutide in hemoglobin A1c reduction. It is also helpful for chronic weight loss and has cardioprotective effects.