Retatrutide vs tirzepatide and semaglutide: the trial numbers side by side

By Retatrutide Risk editorial team. Published September 21, 2026. Sources at the end of the page.

Retatrutide is usually described as the successor to tirzepatide, and tirzepatide as the successor to semaglutide. The description is right about the pharmacology and right about the size of the weight loss, but a comparison of the trials shows that each step up in efficacy has come with a step up in dropouts because of side effects. This page places the pivotal obesity trials side by side and explains what such a comparison can and cannot show.

The three drugs

Mounjaro and Zepbound are the same molecule, tirzepatide, sold under two names for two indications. A search for "retatrutide vs Mounjaro" is therefore a search for retatrutide versus tirzepatide.

Weight loss in the pivotal obesity trials, without diabetes

SURMOUNT-1 also reported -15.0% at 5 mg and -19.5% at 10 mg. TRIUMPH-1 reported -19.0% at 4 mg and -25.9% at 9 mg.

The retatrutide phase 2 result at 48 weeks already exceeded the tirzepatide result at 72 weeks, and the phase 3 result at 80 weeks is larger again. The difference between the top doses of tirzepatide and retatrutide in their pivotal trials is 7.4 percentage points of body weight.

Proportion reaching large weight loss

The thresholds reported differ between trials because each sponsor chose thresholds appropriate to its result; they are not directly comparable, but they show the shift in what counts as a headline number.

Weight loss in type 2 diabetes

Both drugs produce less weight loss in people with type 2 diabetes than in people without it. The retatrutide phase 2 trial also included dulaglutide 1.5 mg, a GLP-1 receptor agonist, which produced -2.02% over 36 weeks, and reported HbA1c reductions of 1.99% to 2.02% at 8 mg and 12 mg versus 1.41% with dulaglutide.

Tolerability: the cost of each step

The STEP 1 figure counts only gastrointestinal discontinuations and is therefore a lower bound for all-cause adverse-event discontinuation. Even so, the ordering is consistent: each additional receptor has brought more weight loss and more participants leaving because of side effects. At its lowest phase 3 dose, 4 mg, retatrutide's discontinuation rate matched placebo while delivering -19.0%, close to tirzepatide's top dose.

The nature of the side effects is the same across all three: nausea, diarrhea, vomiting and constipation, mostly mild to moderate, concentrated during dose escalation. Two items appear with retatrutide that are not prominent in the comparators. Heart rate increased in a dose-dependent way in the phase 2 obesity trial, peaking at 24 weeks; the tirzepatide label reports a mean increase of 1 to 3 beats per minute in its obesity trials. And dysesthesia was reported in 12.3% to 12.5% of TRIUMPH-1 participants on 9 and 12 mg and 20.9% of TRIUMPH-4 participants on 12 mg, versus 0.2% to 0.4% in the tirzepatide label. The side effects article has the detail.

Why cross-trial comparison is limited

• Different populations. Baseline weight, BMI, age, sex and ethnicity differ. SURMOUNT-1 participants had a mean baseline weight of 104.8 kg and BMI of 38.0; TRIUMPH-4 participants averaged 112.7 kg and BMI 40.4.
• Different durations. 48, 68, 72 and 80 weeks. Weight loss curves had not flattened by 48 weeks in the retatrutide phase 2 trial.
• Different estimands. The retatrutide phase 3 figures are the efficacy estimand (effect while on treatment) from press releases; the published tirzepatide and semaglutide figures are from full papers with both estimands available.
• Peer review. STEP 1, SURMOUNT-1, SURMOUNT-2 and the retatrutide phase 2 trials are published. The TRIUMPH figures are company announcements.
• No head-to-head trial. Lilly has registered a trial comparing retatrutide with semaglutide in type 2 diabetes (TRANSCEND-T2D-2, NCT06260722), but no result is published, and no head-to-head trial against tirzepatide in obesity has been reported.

What the comparison supports

Three statements survive the caveats. Retatrutide produced more weight loss than tirzepatide or semaglutide did in their own pivotal trials, by a margin larger than the differences in trial design would plausibly explain. Retatrutide's top dose produced more adverse-event discontinuation than the top doses of the other two. And retatrutide, unlike the other two, is not approved, has no label, and cannot be obtained as a medicine. The FDA approval article covers the last point and the results article the first.