Semaglutide 25 mg Oral Versus Semaglutide 2.4 mg Injectable: An Indirect Treatment Comparison of Weight Loss Outcomes.
Semaglutide just put another notch on its research belt. A new analysis comparing oral semaglutide 25 mg and injectable semaglutide 2.4 mg says both versions hit nearly identical weight loss results. Researchers pulled data from two strong clinical trials—OASIS 4 for the oral option, STEP 1 for the once-weekly injection. The aim: see if swallowing your peptide could actually match a shot in terms of research outcomes.
Diabetes Obes Metab
by Plotkin M, Ivkovic M, Smith I et al.
“Semaglutide 25 mg Oral Versus Semaglutide 2.4 mg Injectable: An Indirect Treatment Comparison of Weight Loss Outcomes. Plotkin M(1), Ivkovic M(2), Smith I(3), Rathor N(2), Chowdhury R(4), Hodkinson A(4), Kushner RF(5). Author information: (1)Novo Nordisk Inc., Plainsboro, New Jersey, USA. (2)Novo Nordisk A/S, Søborg, Denmark. (3)White Box Health Economics Ltd, Brighton & Hove, UK. (4)Petauri Evidence, Bicester, UK. (5)Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. AIMS: Semaglutide, a GLP-1 receptor agonist, has demonstrated significant weight loss benefits for patients with overweight or obesity in both oral and subcutaneous (s.c.) formulations. Given comparable systemic exposure between formulations, an indirect treatment comparison (ITC) was conducted to confirm comparable efficacy. MATERIALS AND METHODS: A naïve Bucher ITC was conducted using data from two well-matched randomized controlled trials: OASIS 4 (once-daily oral semaglutide 25 mg vs. placebo) and STEP 1 (once-weekly s.c. semaglutide 2.4 mg vs. placebo). Both studies enrolled adults with obesity or overweight with ≥ 1 weight-related complication and implemented similar lifestyle changes alongside semaglutide/placebo. The ITC compared percentage change in body weight, the proportion of participants achieving ≥ 5%, ≥ 10%, ≥ 15%, ≥ 20% weight loss, changes in cardiometabolic parameters, and quality of life (IWQoL-Lite-CT PF). Safety outcomes were descriptively compared. RESULTS: Oral and s.c. semaglutide delivered comparable efficacy across all outcomes assessed. While small numerical advantages favoured oral or s.c. semaglutide on some endpoints, the differences and associated uncertainty supported therapeutic equivalence. For percentage weight change, s.c. semaglutide showed a small numerical advantage (estimated treatment difference [ETD]: 1.01%-points (95% confidence intervals [CI]: -1.61, 3.63) under treatment regimen; 0.55%-points (95% CI: -2.25, 3.35) under efficacy), but well below the FDA's 5% threshold for clinical relevance. Safety profiles were broadly comparable. CONCLUSIONS: This ITC suggests that oral semaglutide 25 mg and s.c. semaglutide 2.4 mg offer comparable efficacy for weight management in adults with obesity. © 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.”
Both groups included adults dealing with obesity or overweight, all receiving the same lifestyle tweaks alongside their semaglutide or placebo. The indirect comparison method isn’t as bulletproof as a head-to-head trial, but the data lines up well: weight change, hitting key bodyweight milestones, and even quality of life improvements all looked basically the same.
The headline numbers:
Percentage bodyweight reductions were close, with injectables showing a tiny numerical edge—well under anything the FDA would call “clinically relevant”
Both forms helped more participants hit significant weight loss thresholds (≥5%, ≥10%, etc.)
Safety profiles were similar, so no clear winner there
Key takeaway: oral semaglutide 25 mg and injectable semaglutide 2.4 mg appear equally effective for weight management in adult research subjects. If you’re studying semaglutide, this opens the door to testing both forms—without worrying about major efficacy trade-offs.
Check out the full semaglutide profile for deeper background, or browse the vendor directory if you’re sourcing these research compounds. Both oral and injectable semaglutide continue to deliver for the research community.
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