Wegovy vs Zepbound: Which Loses More Weight?
Reviewed by Sydney Duong, RD, GLPeak Clinical Lead · Last updated 2026-06-17
Quick answer: In the SURMOUNT-5 head-to-head trial, Zepbound 15 mg produced ~20.2% average weight loss over 72 weeks versus ~13.7% on Wegovy 2.4 mg. Zepbound's dual GIP/GLP-1 mechanism appears to drive the difference. Choice between them still depends on insurance, tolerability, and prescriber preference.
Different molecules, different mechanisms
Wegovy is semaglutide, a single-agonist that activates only the GLP-1 receptor. Zepbound is tirzepatide, a dual-agonist that activates both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide). GIP appears to amplify the satiety and metabolic effects.
Head-to-head trial results
SURMOUNT-5 (2025) directly compared the two over 72 weeks in adults with obesity but without diabetes.
- Zepbound 15 mg: ~20.2% average weight loss
- Wegovy 2.4 mg: ~13.7% average weight loss
- More Zepbound patients reached ≥25% weight loss
Side-effect tolerability
Both share the same GI side-effect profile (nausea, constipation, reflux, fatigue). In SURMOUNT-5, discontinuation rates were similar. Some patients tolerate one better than the other for reasons that aren't fully understood.
Cost and access
List prices are similar (~$1,000–$1,350/month for pens). Eli Lilly's LillyDirect vial program for Zepbound offers self-pay pricing of ~$349–$499/month, generally lower than Novo Nordisk's Wegovy self-pay options. Insurance coverage varies by plan.
Frequently asked questions
Is Zepbound better than Wegovy?
On average and at maximum doses, Zepbound produced more weight loss than Wegovy in the SURMOUNT-5 head-to-head trial (~20.2% vs ~13.7% over 72 weeks). 'Better' for an individual still depends on cost, insurance coverage, and how well each is tolerated.
Can I switch from Wegovy to Zepbound?
Yes, with prescriber guidance. There's no direct dose conversion because the molecules differ. A common approach is to restart at Zepbound 2.5 mg for 4 weeks, then move to 5 mg, regardless of prior Wegovy dose.
Do they have the same side effects?
Mostly yes — nausea, constipation or diarrhea, reflux, and fatigue are the most common for both. The intensity varies by individual and dose.
Which is cheaper, Wegovy or Zepbound?
Self-pay through LillyDirect generally makes Zepbound vials cheaper than Wegovy. Through insurance, prices depend on your plan's formulary tier and prior-authorization requirements.
References
Related GLPeak tools
Educational only — not medical advice. Consult your prescriber before changing any medication.