Retatrutide vs Ozempic, Wegovy & Zepbound: Which One Actually Wins?

On paper, retatrutide produces the most weight loss: about 28% on the top dose over 80 weeks, versus roughly 15% for Wegovy (semaglutide 2.4 mg) and 20% to 21% for Zepbound (tirzepatide). But retatrutide is still investigational, and it hasn't been tested head-to-head against any of them yet. Ozempic is the diabetes brand of semaglutide and isn't designed or dosed for maximum weight loss at all.

So the honest answer to "which one wins" depends on what you mean: biggest trial number, strongest direct evidence, or something you can actually get prescribed today.

These numbers come from different trials with different people, doses and lengths, so they aren't a leaderboard. They're the best each drug has shown in its own main study.

Semaglutide acts on one receptor, GLP-1. Retatrutide acts on three: GIP, GLP-1 and glucagon. The glucagon piece is the new part. It's thought to raise energy use and help clear fat from the liver, on top of the appetite effects shared with semaglutide. New to the drug? Start with what retatrutide is.

In their main obesity trials, people lost about 15% on Wegovy 2.4 mg and about 25% to 28% on retatrutide 12 mg. Ozempic, which tops out at 2 mg for diabetes, produced smaller losses because it was studied in people with type 2 diabetes at lower doses.

What semaglutide has that retatrutide doesn't yet: years of real-world use, proven heart protection in the SELECT and SUSTAIN-6 trials, a pill version, and approval. In TRIUMPH-3, retatrutide didn't show a statistically significant reduction in major heart events, though event numbers were low.

Zepbound is the closest relative: it shares the GIP and GLP-1 targets and adds no glucagon. It's also the only drug with a published head-to-head win in this group. In SURMOUNT-5, 751 adults with obesity lost 20.2% on tirzepatide versus 13.7% on semaglutide over 72 weeks.

Retatrutide hasn't faced tirzepatide directly yet. That's the job of TRIUMPH-5, which runs to the end of 2026. Until then, the gap between 28% and 21% is a cross-trial comparison, which can be skewed by differences in starting weight, trial length and how dropouts are counted. For the full comparison, see retatrutide vs tirzepatide.

All four cause the same core side effects: nausea, vomiting, diarrhea and constipation, worst while the dose is going up. Retatrutide's rates look higher at its top dose. In TRIUMPH-1, nausea affected 42.4% of people on 12 mg, vomiting 25.3%, and 11.3% stopped because of side effects. Retatrutide also causes dysesthesia, an unusual skin sensitivity, in about 12% of people on the higher doses, which isn't a typical semaglutide or tirzepatide side effect. Details on our side-effects page.

For the full breakdown of retatrutide's trial numbers, read retatrutide weight loss results, and for timing, our approval watch.

Retatrutide has the most impressive weight-loss numbers, but you can't get it outside a trial, and it hasn't been compared directly with semaglutide or tirzepatide. Today, Wegovy and Zepbound are the approved weight-loss options, and Ozempic is the diabetes brand. If retatrutide is approved, likely in 2027 or 2028, the TRIUMPH-5 results will tell us whether its edge holds up head-to-head.