Efficacy and Safety of Oral Semaglutide in the Management of Diabetes and Obesity: A Comprehensive Meta-analysis of Real-world Evidence.

BACKGROUND: Oral semaglutide is the only oral glucagon-like peptide-1 receptor agonist approved for type 2 diabetes (T2D) management. Although its efficacy and safety are established from randomized controlled trials (RCTs), real-world evidence (RWE) may differ. No comprehensive systematic review and meta-analysis (SRM) has holistically analysed the RWE on oral semaglutide. This SRM analysed the RWE outcomes of oral semaglutide. METHODS: Electronic databases were searched for real-world studies reporting outcomes in adults with T2D receiving oral semaglutide. Primary outcomes were changes in glycated haemoglobin (HbA1c) at 6 and 12 months. Secondary outcomes included changes in body mass index, blood pressure, lipids and adverse events (AEs). Subgroup analyses compared outcomes between Asian and non-Asian cohorts. RESULTS: A total of 59 studies (24,859 individuals) were analysed. The pooled mean HbA1c reduction was -1.11% (95% confidence interval: -1.37 to -0.86; I²=98.8%) at 6 months and -1.19% at 12 months, with 54.7% achieving HbA1c <7%. Weight reduction averaged -4.38 kg at 6 months and -5.96 kg at 12 months. Significant improvements were observed in cardiometabolic parameters. The pooled prevalence of total AEs, gastrointestinal AEs, nausea, diarrhoea and hypoglycaemia was 28.9%, 20.5%, 12.5%, 5.9% and 2.2%, respectively. Discontinuation and dose reduction due to AEs occurred in 8.7% and 4.2% of patients, respectively. Efficacy and safety outcomes were consistent across regions (p for subgroup >0.05). CONCLUSION: Oral semaglutide demonstrates robust real-world efficacy and safety in T2D and obesity management, similar to RCTs, consistent across Asian and non-Asian populations.