Retatrutide Doubled Ozempic’s Weight Loss, With Stomach Side Effects About Even
In the first phase 3 trial to put them side by side, Eli Lilly’s experimental weekly shot took off 20.9% of body weight against Ozempic’s 9.4%. The stomach rows came out close, with one tilt toward diarrhea and more people quitting the top dose.
In Eli Lilly’s TRANSCEND-T2D-2 trial, announced October 28, 2026, retatrutide 12 mg cut body weight 20.9% at 80 weeks against 9.4% on Ozempic 2 mg, with similar nausea (23.8% vs 21.3%), more diarrhea (32.7% vs 26.4%), less constipation (13.1% vs 19.8%), and more people stopping for side effects (7.9% vs 2.7%), per Lilly’s release.
Picture two weekly pens on the same kitchen counter. One is Ozempic, the drug that made the whole category a household word. The other is retatrutide, Eli Lilly’s experimental shot, and on Wednesday morning it posted more than twice the weight loss in the first phase 3 trial to put the two side by side. We read the release line by line, pulled the trial registration and the earlier retatrutide studies, and asked the question most people taking these drugs ask first: what does the new one do to your stomach?
The short answer is that the stomach numbers came out close to even, with one tilt and one cost. Diarrhea ran a little higher on retatrutide, constipation ran clearly lower, and more people on the top dose stopped treatment because of side effects. Here is each piece, with the numbers.
The result: in Lilly’s TRANSCEND-T2D-2 trial, announced October 28, 2026, adults with type 2 diabetes on retatrutide lost 19.5% (9 mg) and 20.9% (12 mg) of body weight at 80 weeks, against 9.4% on Ozempic 2 mg.
The stomach: diarrhea 28.3% and 32.7% on retatrutide vs 26.4% on Ozempic; nausea 21.2% and 23.8% vs 21.3%; constipation 14.2% and 13.1% vs 19.8%, per the Lilly release.
The trade-off: 4.8% (9 mg) and 7.9% (12 mg) stopped retatrutide because of side effects, vs 2.7% on Ozempic; 7.9 is about 2.9 times 2.7 (our arithmetic).
The status: retatrutide is investigational, not approved anywhere, and these are company-reported topline results, not yet peer reviewed.
Sources: Eli Lilly release, Oct 28, 2026; ClinicalTrials.gov NCT06260722. Educational, not medical advice.
The trial: Retatrutide more than doubled Ozempic’s weight loss over 80 weeks
TRANSCEND-T2D-2 enrolled 1,298 adults with type 2 diabetes whose blood sugar was not controlled on metformin, with or without an SGLT2 pill, according to Lilly’s October 28 release. They were randomized two to two to one to retatrutide 9 mg, retatrutide 12 mg or Ozempic 2 mg, the highest approved Ozempic dose, all once a week. The trial was open label, meaning participants knew which drug they were on; the ClinicalTrials.gov record for NCT06260722 lists its masking as none.
At 80 weeks, retatrutide lowered A1C, the three-month blood sugar average, by 2.2 points at both doses against 1.8 on Ozempic, from a starting average of 8.3%. Weight fell 19.5% on 9 mg (44.3 pounds) and 20.9% on 12 mg (47.4 pounds), against 9.4% (20.9 pounds) on Ozempic, from a starting average of 225.8 pounds. By our arithmetic that is 2.1 and 2.2 times the Ozempic result. Lilly reports these figures as the efficacy estimand, which assumes everyone stayed on their drug for the full 80 weeks.
Retatrutide works on three hormone receptors at once: GLP-1, the target Ozempic hits, plus GIP and glucagon. In Lilly’s obesity trial TRIUMPH-1, published in the New England Journal of Medicine on September 29, people without diabetes lost 23.7% and 25.0% on the same two doses. Weight loss has historically been harder for people with type 2 diabetes, the release notes, which is why the trial population matters when comparing numbers.
“In TRANSCEND-T2D-2, the first Phase 3 trial comparing retatrutide with another incretin medicine, retatrutide delivered greater A1C reduction and more than double the weight loss of the highest approved dose of Ozempic for type 2 diabetes.” Kenneth Custer, president of Lilly Cardiometabolic Health, October 28, 2026
The stomach: Diarrhea ran a little higher on retatrutide, constipation clearly lower
| At 80 weeks | Retatrutide 9 mg | Retatrutide 12 mg | Ozempic 2 mg |
|---|---|---|---|
| Weight change | -19.5% | -20.9% | -9.4% |
| Diarrhea | 28.3% | 32.7% | 26.4% |
| Nausea | 21.2% | 23.8% | 21.3% |
| Constipation | 14.2% | 13.1% | 19.8% |
| Vomiting | 10.2% | 15.0% | 13.2% |
| Indigestion (dyspepsia) | 10.4% | 8.5% | 11.6% |
| Stopped for side effects | 4.8% | 7.9% | 2.7% |
The five most common side effects in the trial were all digestive, and the retatrutide rows sit close to the Ozempic row. Nausea was 21.2% on retatrutide 9 mg and 23.8% on 12 mg against 21.3% on Ozempic, effectively a tie at the lower dose. Vomiting was 10.2% and 15.0% against 13.2%, lower on 9 mg and higher on 12 mg. Indigestion was 10.4% and 8.5% against 11.6%, lower on both. Lilly says most of these events were mild to moderate and typically resolved during treatment.
The two rows that move are diarrhea and constipation, and they move in opposite directions. Diarrhea was 28.3% and 32.7% on retatrutide against 26.4% on Ozempic, so 1.9 and 6.3 percentage points higher. Constipation was 14.2% and 13.1% against 19.8%, so 5.6 and 6.7 points lower (our arithmetic). Put as a ratio, Ozempic users in this trial reported diarrhea about 1.3 times as often as constipation; on retatrutide 12 mg it was about 2.5 times. Our reading: the retatrutide profile leans toward the loose end of the bowel. The release does not say why, and a topline does not settle it.
That matches what people are already searching. The completions for “retatrutide diarrhea” on Wednesday included “how long does it last”, “after eating” and “how to stop”. If you take a GLP-1 drug and the issue is the opposite, our read of what the labels say about poop frequency covers the constipation side.
The cost: More people on the top dose stopped because of side effects
The side-effect rates are close; the quit rates are not. In TRANSCEND-T2D-2, 4.8% of people on retatrutide 9 mg and 7.9% on 12 mg stopped treatment because of adverse events, against 2.7% on Ozempic. By our arithmetic the top dose had about 2.9 times the Ozempic quit rate, or roughly 8 people in 100 against 3. Lilly’s release counts all adverse events there, not just digestive ones; it also lists dysesthesia, an unusual skin sensation, at 4.8% and 6.5% against 2.7%.
The dosing ladder matters too. Every retatrutide user started at 2 mg and stepped up every four weeks. In the 2023 phase 2 obesity trial in the New England Journal of Medicine, digestive side effects were dose-related and were partly reduced by starting at 2 mg rather than 4 mg. In the 2023 phase 2 diabetes trial in The Lancet, 35% of retatrutide users and 35% of dulaglutide users reported digestive side effects, against 13% on placebo.
The mechanism: Why weekly shots like these upset the stomach at all
The shared culprit is GLP-1 itself. In a 1997 study in the American Journal of Physiology, Nauck and colleagues showed that GLP-1 slows how fast the stomach empties, an effect strong enough to shape the blood sugar response on its own. Food sitting longer in the stomach is part of why these drugs make people feel full, and part of why nausea, burping and indigestion are so common early on. We cover the full picture for Ozempic in what Ozempic does to your gut and for Lilly’s pill in our read of Foundayo; for the nausea itself, see the motion-sickness pill tested against Wegovy vomiting.
The everyday version stays the same whichever pen it is: smaller meals, slower eating, enough water, and fiber built up gradually. Our guide to getting enough fiber on a GLP-1 goes through it.
What it is not: Retatrutide is not approved and cannot legally be sold
Retatrutide is investigational. Lilly’s release states it has not been approved by the FDA or any regulator anywhere, and that anyone purporting to sell it to consumers is breaking the law. The autocomplete for “retatrutide” includes “peptide” and “dosage calculator”, which suggests people are finding it outside a trial; nothing in these results describes those products. Lilly is also running TRIUMPH-5, a head-to-head trial against its own tirzepatide, the drug in Mounjaro and Zepbound. Detailed TRANSCEND-T2D-2 results are due at a future medical meeting and in a peer-reviewed journal.
How we checked this: Sources and method
We read Eli Lilly’s October 28, 2026 release on PR Newswire (06:45 ET) at source for every efficacy and side-effect figure, and the ClinicalTrials.gov record NCT06260722 for the design and masking. These are company-reported topline results, not yet peer reviewed. The earlier studies are cited by PubMed ID, each matched to its title: PMID 42814954 (TRIUMPH-1, NEJM 2026), 37366315 (phase 2 obesity, NEJM 2023), 37385280 (phase 2 type 2 diabetes, Lancet 2023) and 9374685 (GLP-1 and gastric emptying, 1997). Search completions were read from Google autocomplete on October 28. Differences, ratios and per-100 figures are our arithmetic. This article is educational, describes what the cited sources say, and is not medical advice.