Oral Semaglutide for the Treatment of Type 2 Diabetes: A Mini Review

Abstract

Objective: To review efficacy and safety of the first orally available glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide. Methods: PubMed search published in English, French and Spanish from January 2000 until September 04, 2019. Search terms included “oral semaglutide”, “semaglutide”, “GLP-1 receptors”, “clinical trials”, “absorption”, “metabolism”, “efficacy”, “safety”, “cardiovascular”, “kidney disease”. Randomized trials, review articles, expert opinions and editorials are included in the review. Results: Oral semaglutide is effectively absorbed in the stomach by absorption enhancer, but has to be taken in the fasting state with water, and no food allowed for 30 min after intake. It is generally comparable in efficacy to the subcutaneous form of semaglutide. When compared to liraglutide, oral semaglutide is slightly superior in decreasing hemoglobin A1c (HbA1c) (-0.3% vs. liraglutide) and weight (-1.3 kg vs. liraglutide), but is associated with more frequent adverse effects (reported by 80% vs. 74% of patients). Oral semaglutide was more effective than sitagliptin. Limited data suggest that oral semaglutide is safe and effective in patients with moderate degree of renal impairment. A large randomized trial of median follow-up of 15.9 months, showed that oral semaglutide was non-inferior to placebo in terms of cardiovascular events and mortality, and might have beneficial effects on reducing some of these events. Conclusion: Oral semaglutide has an efficacy and safety profile consistent with the class of GLP-1 receptor agonists. It represents a useful therapeutic option for patients with type 2 diabetes who are reluctant to take injections. Further studies are needed to establish its long-term efficacy and safety in a large population of type 2 diabetes, including those with chronic kidney disease.