Eli Lilly’s experimental drug retatrutide beat Novo Nordisk’s Ozempic on both blood sugar control and weight loss in a head-to-head Phase 3 trial, the company announced on Wednesday, 28 October. In the 80-week TRANSCEND-T2D-2 trial, people taking retatrutide lost more than twice as much weight on average as those taking Ozempic, and lowered their blood sugar further.
Retatrutide remains investigational: it has not been approved by the US Food and Drug Administration or any other regulator, and these are topline results announced by the company, not yet published in a peer-reviewed journal. The results should be read with that status in mind, and this article is a report of the trial results, not medical advice.
The trial
TRANSCEND-T2D-2 enrolled 1,298 adults with type 2 diabetes whose blood sugar was inadequately controlled on metformin, with or without an SGLT2 inhibitor. Participants started with an average A1C — a measure of average blood sugar over time — of 8.3%, an average weight of 102.4 kilograms (225.8 pounds) and an average body mass index of 36.8.
Participants were randomised 2:2:1 to once-weekly retatrutide 9 mg, retatrutide 12 mg, or Ozempic 2 mg. Retatrutide started at 2 mg and was increased every four weeks to the target dose. The trial’s primary objective was to show that retatrutide 12 mg was noninferior to Ozempic 2 mg in reducing A1C at 80 weeks; Lilly reports that the primary endpoint and all key secondary endpoints were met.
One important caveat: Lilly states the results are for the efficacy estimand — that is, they estimate the effect if participants had stayed on their assigned treatment for 80 weeks without starting additional diabetes medication for more than 14 days. They are not a simple average across every randomised participant regardless of what happened during the trial.
The results
At 80 weeks, both retatrutide doses lowered A1C by an average of 2.2 percentage points, compared with 1.8 percentage points for Ozempic 2 mg. On weight, participants on retatrutide 9 mg lost an average of 44.3 pounds (20.1 kg), or 19.5% of body weight, and those on 12 mg lost an average of 47.4 pounds (21.5 kg), or 20.9%. Participants on Ozempic lost an average of 20.9 pounds (9.5 kg), or 9.4%.
Lilly also reported greater improvements on retatrutide than on Ozempic across certain cardiovascular risk factors, including non-HDL cholesterol, triglycerides and systolic blood pressure, but no numeric values for those measures were given in the announcement, so none are quoted here.
The comparison is specifically against Ozempic 2 mg, which Lilly and Reuters describe as the highest approved dose of Ozempic for type 2 diabetes. It is not a comparison against Wegovy, Novo Nordisk’s higher-dose obesity medicine, or any investigational semaglutide dose.
What retatrutide is
Retatrutide is a once-weekly, single-molecule drug that activates three hormone receptors at once — GIP, GLP-1 and glucagon — earning it the nickname “triple-G”. Ozempic (semaglutide) acts on GLP-1 only. The idea behind combining three signals is to add appetite suppression and blood sugar control to increased calorie burning, though that mechanism is still being tested in trials.
Kenneth Custer, president of Lilly Cardiometabolic Health, said: “Based on these results and those from across our Phase 3 program, we believe retatrutide, if approved, could shift the treatment paradigm for people living with type 2 diabetes, obesity and related cardiometabolic conditions.” Lilly describes this as the first Phase 3 trial comparing retatrutide directly with another incretin medicine, and the sixth Phase 3 trial in which retatrutide has shown strong efficacy. A separate head-to-head trial against tirzepatide, called TRIUMPH-5, is ongoing and its results have not been reported.
Safety: more stomach side effects, more discontinuations
The most common side effects on retatrutide were stomach-related. Diarrhoea affected 28.3% of participants on 9 mg and 32.7% on 12 mg, compared with 26.4% on Ozempic; nausea affected 21.2% and 23.8%, compared with 21.3%; and vomiting affected 10.2% and 15.0%, compared with 13.2%. Most events were described by Lilly as mild to moderate.
More people stopped retatrutide because of side effects than stopped Ozempic: 4.8% on the 9 mg dose and 7.9% on the 12 mg dose, compared with 2.7% on Ozempic. That trade-off — greater weight loss and blood sugar reduction, with a higher chance of stopping treatment because of side effects, especially at the higher dose — is a central part of the trial picture.
What happens next
Lilly says detailed results from TRANSCEND-T2D-2 will be presented at a future medical meeting and published in a peer-reviewed journal; no meeting, journal or date has been given. BioSpace reports Lilly plans to file for approval in the first quarter of 2027. That is a filing plan, not an approval date, and no approval timeline should be inferred from it. No response from Novo Nordisk to these results was found at the time of writing, and none is attributed here.
FAQ
Is retatrutide approved? No. It is an investigational molecule that has not been approved by the FDA or any other regulator anywhere in the world.
How much weight did participants lose? At 80 weeks, an average of 19.5% on retatrutide 9 mg and 20.9% on 12 mg, compared with 9.4% on Ozempic 2 mg — in the efficacy-estimand analysis reported by Lilly.
Was this a comparison with the strongest Ozempic dose? The comparator was Ozempic 2 mg, the highest approved dose for type 2 diabetes. It was not a comparison with Wegovy or a higher semaglutide dose.
When will full results appear? Lilly says detailed results will be presented at a future medical meeting and published in a peer-reviewed journal, with no date given.
Sources
- Eli Lilly and Company via PR Newswire, “Lilly’s retatrutide delivered greater A1C reduction and more than double the weight loss of Ozempic’s highest approved dose in head-to-head trial”, 28 Oct 2026: https://crweworld.com/article/news-provided-by-pr-newswire/3938308/lillys-retatrutide-delivered-greater-a1c-reduction-and-more-than-double-the-weight-loss-of-ozempics-highest-approved-dose-in-head-to-head-trial
- Reuters, “Lilly’s next-gen drug outshines Ozempic on weight loss, blood sugar control in trial”, 28 Oct 2026: https://www.reuters.com/legal/litigation/lillys-next-gen-drug-outshines-ozempic-weight-loss-blood-sugar-control-trial-2026-10-28/
- STAT News, “Lilly’s ‘triple-G’ drug bests Ozempic in head to head study”, 28 Oct 2026: https://www.statnews.com/2026/10/28/retatrutide-vs-ozempic-lilly-diabetes-study/
- BioSpace, “Lilly’s retatrutide trounces Novo’s Ozempic in diabetes, weight loss”, 28 Oct 2026: https://www.biospace.com/drug-development/lillys-retatrutide-trounces-novos-ozempic-in-diabetes-weight-loss
- USA Today, “Retatrutide beats Ozempic on weight loss, blood sugar control, study says”, 28 Oct 2026: https://www.usatoday.com/story/money/personal-finance/healthcare/2026/10/28/retatrutide-ozempic-weight-loss-blood-sugar-study/92475741007/
