Taking weekly semaglutide reduced HbA1c levels and increased weight loss more than extended-release exenatide, according to results from the Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) 3. The trial included 813 adults with type 2 diabetes and a baseline HbA1c level of 7.0% to 10.5% who were randomized to either once-weekly subcutaneous extended-release (ER) exenatide, 2.0 mg, by vial and syringe, or once-weekly subcutaneous semaglutide, 0.25 mg for 4 weeks, 0.5 mg for 4 weeks, and 1.0 mg for 48 weeks, by prefilled pen injector.
The study was published in the February 2018 Diabetes Care. The following commentary by Eleni Bekiari, MD, MSc, PhD; Thomas Karagiannis, MD, MSc; and Apostolos Tsapas, MD, MSc, PhD, was published in the ACP Journal Club section of the April 17 Annals of Internal Medicine.
Current guidelines recommend glucagon-like peptide-1 analogues as second- or third-line agents for patients with type 2 diabetes. Findings of the SUSTAIN-3 trial suggest that once-weekly semaglutide could be preferred over once-weekly exenatide based on reductions in HbA1c levels and body weight. Nevertheless, exenatide is an effective alternative for patients who cannot tolerate semaglutide due to gastrointestinal adverse events. The validity of trial conclusions is undermined by the choice of device used to administer exenatide (syringe), which differs from the currently available option (prefilled pen) and may have led to decreased adherence, efficacy, and adverse effects.
These findings should be placed in the context of SUSTAIN-6 and Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results trials, which reported reductions in cardiovascular disease with semaglutide and liraglutide added to usual care, respectively. However, the Exenatide Study of Cardiovascular Event Lowering trial reported no difference with the addition of exenatide to usual care. Nevertheless, it is questionable whether the benefits in cardiovascular outcomes can be attributed to the efficacy of semaglutide and liraglutide in reducing HbA1c levels or body weight, or to multiple parameters that affect progression of atherosclerosis.