Short answer
Retatrutide has the highest single trial result (24.2%, Phase 2). Tirzepatide has the highest confirmed Phase 3 result (20.9%) among approved drugs. For a patient making a treatment decision today, tirzepatide is the most effective available option.
Complete Ranking: Weight Loss by Drug
| Drug | Status | Avg Weight Loss | Trial Duration | Phase |
|---|---|---|---|---|
| Retatrutide (12mg) | Phase 3 (not approved) | 24.2% | 48 weeks | Phase 2 |
| CagriSema | Phase 3 (not approved) | 22.7% | 68 weeks | Phase 3 |
| Tirzepatide (Zepbound, 15mg) | Approved (obesity) | 20.9% | 72 weeks | Phase 3 |
| Tirzepatide (Mounjaro) | Approved (diabetes) | ~20% | 72 weeks | Phase 3 |
| MariTide | Phase 3 (not approved) | ~20% | 52 weeks | Phase 2 |
| Semaglutide (Wegovy, 2.4mg) | Approved (obesity) | 14.9% | 68 weeks | Phase 3 |
| Semaglutide (Ozempic, 1mg) | Approved (diabetes) | ~6-7% | 40 weeks | Phase 3 |
| Orforglipron (120mg) | Phase 3 (not approved) | 14.7% | 36 weeks | Phase 2 |
| Liraglutide (Saxenda) | Approved (obesity) | ~8% | 56 weeks | Phase 3 |
| Semaglutide oral (Rybelsus) | Approved (diabetes) | ~5-8% | 26-68 weeks | Phase 3 |
What Drives These Differences
Higher weight loss correlates with broader receptor engagement. Drugs targeting only GLP-1 (semaglutide, liraglutide) produce the least weight loss in the ranking. Adding GIP (tirzepatide) increases it substantially. Adding glucagon on top (retatrutide) increases it further. Adding amylin instead of GIP (CagriSema) achieves similar results through a different mechanism.
Dose also matters significantly. Tirzepatide at 15mg produces 20.9% average weight loss; lower doses produce less. The weight loss numbers above represent the highest dose tested in each trial.
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Get My Match →What This Means for a Real Patient
If maximum weight loss is the primary goal and you're making a decision today: tirzepatide (Zepbound) is the evidence-based answer. It's approved, accessible through telehealth, and has the strongest Phase 3 dataset of any currently available drug.
If you have health reasons that make tirzepatide contraindicated or if you're needle-averse: semaglutide (Wegovy) at 14.9% is still a clinically meaningful result that exceeds what any medication produced before 2021.
See individual drug profiles: retatrutide, CagriSema, or the complete comparison hub.
Frequently Asked Questions
Which GLP-1 is the most effective for weight loss?
Retatrutide has the highest Phase 2 data (~24%) but isn't approved. Among approved drugs, tirzepatide (Zepbound/Mounjaro) at 20-22% is the most effective.
How much weight can I expect to lose on tirzepatide?
The Phase 3 average is 20.9% at 72 weeks on the highest dose. Individual results vary — some people lose more, some less. Starting weight, adherence, lifestyle factors, and biological response all affect outcomes.
Is 15% weight loss on Wegovy considered good?
Yes. 15% of body weight is a clinically meaningful result. For someone at 250 lbs, that's 37.5 lbs. Before 2021, this was not achievable through any medication.
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