Retatrutide vs Tirzepatide: What the Trials Show So Far

Written by Olha Orlyk. Updated October 22, 2026.

Retatrutide has produced more average weight loss than tirzepatide in their separate trials: up to 28.3% over 80 weeks on retatrutide 12 mg, versus up to 20.9% over 72 weeks on tirzepatide 15 mg. But the two have not yet been tested against each other. That head-to-head trial, TRIUMPH-5, runs to the end of 2026. And only one of them is something you can get today: tirzepatide is FDA-approved as Mounjaro and Zepbound, while retatrutide is still investigational.

Both come from Eli Lilly, and retatrutide is essentially tirzepatide's successor: it keeps the same two hormone targets and adds a third. Here's how they compare on mechanism, results, side effects and availability.

Tirzepatide activates two gut-hormone receptors, GIP and GLP-1, which cut appetite, slow stomach emptying and improve blood sugar. Retatrutide hits the same two and adds the glucagon receptor. Glucagon normally raises blood sugar, which sounds counterproductive, but in this combination the GLP-1 and GIP effects keep glucose in check while the glucagon signal appears to increase energy use and help the liver burn fat.

That third signal is the leading explanation for retatrutide's larger weight loss and its striking liver-fat results in early studies. It's also a plausible reason for differences in side effects, such as a higher resting heart rate.

Read this table with care. The trials ran for different lengths, enrolled different people, and the retatrutide figure uses Lilly's efficacy estimand; the stricter published analysis puts retatrutide 12 mg at 25.0%. Even so, the gap of several percentage points at the top doses is large enough that most experts expect retatrutide to come out ahead in a direct test. The question TRIUMPH-5 will answer is by how much, and at what cost in side effects. For every retatrutide number in detail, see retatrutide weight loss results.

Both drugs cause the same family of stomach and gut side effects, mostly during dose increases. At their top doses, retatrutide's rates look higher, and it adds dysesthesia, an unusual skin sensitivity. Those are cross-trial comparisons, so TRIUMPH-5 matters here too. More on our side-effects page.

For type 2 diabetes, tirzepatide is the established option: Mounjaro lowers A1C by about 2 points in its trials and is widely covered. Retatrutide lowered A1C by up to 2.0 points in TRANSCEND-T2D-1 and produced more weight loss in people with diabetes than tirzepatide did in SURMOUNT-2.

On the heart, neither drug has a completed outcome result that settles the question. In TRIUMPH-3, retatrutide improved blood pressure, triglycerides and inflammation markers in people with heart disease, but didn't significantly reduce major heart events, partly because there were few events.

TRIUMPH-5 randomizes adults with obesity to retatrutide or tirzepatide with no placebo group and runs to the end of 2026. It's designed to show whether retatrutide's advantage holds up when both drugs are tested in the same people under the same rules. Results are likely in 2027, around the time Lilly files retatrutide with FDA. Our approval watch will track it.

Retatrutide looks like the stronger drug for weight loss on paper, by several percentage points at the top doses, thanks largely to its extra glucagon action. It also looks a little harder to tolerate and is not approved. Tirzepatide is the proven, available option. TRIUMPH-5, due to finish at the end of 2026, is the first real test of whether retatrutide's lead survives a fair fight.