Efficacy and safety of oral semaglutide in type 2 diabetes mellitus: A systematic review and meta-analysis

Objectives: To investigate the efficacy and safety of oral semaglutide 7 and 14 mg, the only orally delivered glucagon-like peptide-1 (GLP-1) receptor agonist tablet approved for type 2 diabetes mellitus (T2DM) patients. Methods: Search several databases for randomized controlled trials (RCTs) of oral semaglutide in patients with T2DM from inception through May 31, 2021. The primary outcomes included change from baseline in hemo-globin A1c (HbA1c) and body weight. Risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI) were calculated to evaluate the outcomes. Results: This meta-analysis included 11 RCTs with a total of 9821 patients. Compared with placebo, semaglutide 7 and 14 mg reduced HbA1c by 1.06% (95% CI, 0.81-1.30) and 1.10% (95% CI, 0.88-1.31), respectively. While in comparison with other antidiabetic agents, semaglutide 7 and 14 mg reduced HbA1c by 0.26% (95% CI, 0.15-0.38) and 0.38% (95%CI, 0.31-0.45). Both doses of semaglutide could significantly reduce body weight. Semaglutide 14 mg did increase the incidence of medication discontinuation and gastrointestinal events (nausea, vomiting and diarrhea). Conclusion: Once-daily semaglutide 7 and 14 mg can significantly lowered HbA1c and body weight in patients with T2DM, and this effect increases with dose. Significantly, more gastrointestinal events occurred with sem-aglutide 14 mg.