Oral Wegovy: Early Responders Lost 21.6% at Week 64
New OASIS 4 sub-analyses at ECO 2026 show oral semaglutide 25 mg achieves 21.6% weight loss in early responders — and tops orforglipron on both efficacy and tolerability.
May 20, 2026 · 3 min read
New sub-analyses from the OASIS 4 trial presented at the European Congress on Obesity (ECO 2026, Istanbul, May 12–15) show that oral semaglutide 25 mg achieves 21.6% mean weight loss by week 64 among early responders — patients who lost at least 10% of their body weight by week 16.
What the OASIS 4 Sub-Analyses Found
Novo Nordisk presented three analyses from its Phase 3b OASIS 4 trial, each adding clinical texture beyond the primary outcome data from the trial that supported the drug's December 2025 FDA approval.
Early responder analysis: Among participants, 28.8% qualified as early responders (≥10% weight loss by week 16). This group went on to lose an average of 21.6% of body weight by week 64. Participants who did not meet the early response threshold still achieved 11.5% weight loss by week 64 — a clinically meaningful reduction, though notably lower than the early responder group.
The early responder finding is clinically useful: it suggests that patients who respond well in the first four months of oral semaglutide are likely to see substantially greater long-term benefit, which could inform shared decision-making at the four-month mark.
Functional outcomes: A separate analysis showed that 77.3% of participants with poor physical function at baseline experienced clinically meaningful improvements in both mobility and bodily pain by trial completion. Functional improvement data is increasingly important in regulatory and formulary discussions around obesity medications — outcomes beyond the scale matter for reimbursement decisions.
Head-to-head comparisons: Data from the ORION and OPTIC studies, also presented at ECO 2026, placed oral semaglutide 25 mg above orforglipron 36 mg (Foundayo, approved April 2026) on weight loss outcomes. Oral semaglutide was also associated with lower odds of treatment discontinuation due to gastrointestinal adverse effects, suggesting a tolerability advantage despite the oral GLP-1 class's generally higher GI burden compared to injectables.
Why It Matters
The oral Wegovy pill (once-daily semaglutide 25 mg tablets) has been available since January 2026, following FDA approval on December 22, 2025. The primary OASIS 4 data showed 16.6% mean weight loss at 64 weeks on treatment — a strong result, though lower than injectable semaglutide 2.4 mg's 14.9% in STEP-1 (an indirect comparison with important population and dosing differences).
The ECO 2026 sub-analyses don't change the approval or the primary outcomes, but they sharpen the clinical picture for prescribers:
- The gap between early responders (21.6%) and non-responders (11.5%) is wide. Patients who are doing well at four months are likely to do very well long-term; patients who aren't may benefit from a dose adjustment discussion or a switch to a different formulation.
- The functional improvement data supports a beyond-weight-loss argument for the oral formulation, which may resonate with payers evaluating coverage for the pill against the injectable.
- The orforglipron comparison, while indirect, gives clinicians a preliminary sense of how to think about the two competing oral GLP-1 pills.
What to Watch
Novo Nordisk's oral semaglutide 25 mg faces a competitive landscape: Eli Lilly's Foundayo (orforglipron, approved April 2026) doesn't require the fasting and water restrictions that oral semaglutide does, which could give it an adherence advantage in practice. Whether the weight loss gap seen in the ORION/OPTIC data translates to meaningful real-world differences in outcomes remains to be seen — real-world adherence and dosing behavior in the oral GLP-1 category will shape those numbers significantly.
More OASIS 4 analyses, including longer-term follow-up and metabolic marker data, are expected in peer-reviewed publication over the coming months.
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