Oral Semaglutide Achieves Significant Real-World HbA1c and Weight Reductions, Confirming RCT Efficacy in T2D and Obesity

The global rise in obesity and type 2 diabetes (T2D) necessitates effective, convenient treatments. While injectable glucagon-like peptide-1 receptor agonists (GLP-1RA) are established, oral semaglutide offers a unique, non-injectable option. Its efficacy and safety are proven in randomized controlled trials (RCTs), but real-world evidence (RWE) can sometimes differ due to broader patient populations and less controlled settings. This meta-analysis addresses the gap by comprehensively evaluating oral semaglutide's performance in everyday clinical practice.

This systematic review and meta-analysis synthesized real-world data from 59 studies involving 24,859 individuals with type 2 diabetes receiving oral semaglutide. Researchers searched electronic databases for studies reporting outcomes in adults. The primary endpoints were changes in glycated haemoglobin (HbA1c) at 6 and 12 months. Secondary outcomes included changes in body mass index (BMI), blood pressure, lipids, and adverse events (AEs). Subgroup analyses were conducted to compare outcomes between Asian and non-Asian cohorts.

Oral semaglutide demonstrated robust real-world efficacy, mirroring its performance in RCTs. The pooled mean HbA1c reduction was -1.11% (95% CI: -1.37 to -0.86) at 6 months and -1.19% at 12 months. Notably, 54.7% of patients achieved an HbA1c target of <7%. Significant weight reduction was also observed, averaging -4.38 kg at 6 months and -5.96 kg at 12 months. Improvements extended to other cardiometabolic parameters. The safety profile was consistent, with a pooled prevalence of total AEs at 28.9%, gastrointestinal AEs at 20.5%, nausea at 12.5%, diarrhoea at 5.9%, and hypoglycaemia at 2.2%. Discontinuation due to AEs occurred in 8.7% of patients, and dose reduction in 4.2%. Efficacy and safety outcomes were consistent across regional subgroups (p for subgroup >0.05).