BACKGROUND AND AIMS: Oral semaglutide has undergone global Phase 3 development programs named PIONEER and approved for therapeutic use in people with type 2 diabetes (T2D). We aim to systematically review the efficacy and safety of oral semaglutide in real-world settings.
METHODS: We systematically searched the electronic databases of PubMed, Google Scholar, and ClinicalTrials.gov from inception until March 15, 2024, using several keywords with Boolean "AND". We retrieved all the available granular details of real-world studies (RWS).
RESULTS: To date, results from four prospective and ten retrospective real-world studies of oral semaglutide in T2D are available. In prospective studies, the primary outcome of HbA1c reduction varied from -0.9 % to -1.6 %, weight loss varied from -4.7 kg to -8.2 kg and HbA1c target of <7 % was achieved in 30 %-64 % with oral semaglutide. In retrospective studies, HbA1c reduction varied from -0.4 % to -1.8 %, weight reduction varied from -1.4 to -9.0 kg, HbA1c target of <7 % was achieved in 32-64 %, and 30-41 % of people with T2D had ≥5 % weight loss with oral semaglutide. Gastrointestinal adverse events with oral semaglutide varied from 16 % to 50 % in prospective and 6 %-47 % in retrospective RWS. Overall, 0 %-18 % of patients had oral semaglutide discontinuation due to any cause.
CONCLUSION: Oral semaglutide exhibited a reasonable reduction in HbA1c and weight in people with T2D, consistent with the findings from PIONEER trials. While no new safety issues emerged, the inherent limitations of RWS underscore the necessity of long-term investigations to comprehensively assess safety.