Eli Lilly's experimental weekly injection retatrutide helped adults with type 2 diabetes lose about twice as much weight as semaglutide, the drug in Ozempic, in an 80-week head-to-head Phase 3 trial. Lilly released the topline TRANSCEND-T2D-2 results on 28 October 2026. Retatrutide is not yet approved anywhere.
The trial compared two doses of retatrutide with the highest approved Ozempic dose, semaglutide 2 mg, in 1,298 adults whose diabetes was not controlled on metformin, with or without an SGLT2 inhibitor. RTÉ's News at One, US broadcasters and specialist medical outlets covered the results on 28 and 29 October. The full data have not yet been presented at a medical meeting or published in a peer-reviewed journal, so the figures below are the company's topline numbers.
- Weight loss at 80 weeks: 20.9% of body weight with retatrutide 12 mg and 19.5% with 9 mg, against 9.4% with semaglutide 2 mg.
- Blood sugar: HbA1c fell by 2.2 percentage points on both retatrutide doses and by 1.8 points on semaglutide, from an average of 8.3%.
- Side effects: mostly gastrointestinal. 7.9% (12 mg) and 4.8% (9 mg) stopped retatrutide because of side effects, against 2.7% on semaglutide.
- Status: investigational. Not approved by the FDA, the European Medicines Agency or any other regulator, and not available in Ireland.
- Irish link: Lilly's Kinsale plant in Co Cork makes the active ingredient for its current weight-loss medicine, tirzepatide (Mounjaro).
1. What the TRANSCEND-T2D-2 trial tested
TRANSCEND-T2D-2 (ClinicalTrials.gov NCT06260722) is a randomised, open-label Phase 3 study. Participants were assigned in a 2:2:1 ratio to once-weekly retatrutide 9 mg, retatrutide 12 mg or semaglutide 2 mg. Retatrutide started at 2 mg and was stepped up every four weeks. At the start, the average participant weighed 102.4 kg, had a body mass index of 36.8 and an HbA1c of 8.3%, well above the 7% target commonly used in diabetes care.
The main goal was to show that retatrutide lowers HbA1c at least as well as semaglutide (non-inferiority). Weight change was a key secondary measure. Because the study was open-label, participants and doctors knew which drug was being given, which is common in head-to-head injection trials but worth noting when reading the results.
2. The results in numbers
| Measure | Result |
|---|---|
| Weight loss, retatrutide 12 mg | 20.9% (about 21.5 kg) |
| Weight loss, retatrutide 9 mg | 19.5% (about 20.1 kg) |
| Weight loss, semaglutide 2 mg | 9.4% (about 9.5 kg) |
| HbA1c change, both retatrutide doses | minus 2.2 points |
| HbA1c change, semaglutide 2 mg | minus 1.8 points |
| Stopped due to side effects | 7.9% (12 mg), 4.8% (9 mg), 2.7% (semaglutide) |
The 12 mg dose was statistically superior to semaglutide on HbA1c, not just non-inferior. Both retatrutide doses beat semaglutide on weight. Lilly also reported larger improvements in non-HDL cholesterol, triglycerides and systolic blood pressure, but did not give the size of those differences. The figures use the efficacy estimand, which counts people who stayed on treatment for the full 80 weeks without extra glucose-lowering medicine, so results across everyone who started the trial may be somewhat smaller.
3. Why retatrutide works differently
Semaglutide acts on one gut-hormone receptor, GLP-1. Tirzepatide, sold as Mounjaro, acts on two, GLP-1 and GIP. Retatrutide adds a third target, the glucagon receptor, which is why it is often called a "triple agonist". The glucagon component is thought to raise energy use and help clear fat from the liver, on top of the appetite and blood-sugar effects of the other two hormones.
That extra mechanism may also explain part of the side-effect profile. Diarrhoea was reported by 32.7% on the 12 mg dose, against 26.4% on semaglutide, and vomiting by 15.0% against 13.2%. Constipation and indigestion were less common with retatrutide. Dysaesthesia, an unusual skin sensation, occurred in 6.5% on 12 mg compared with 2.7% on semaglutide. Most side effects were mild to moderate and eased during treatment, according to the company.
4. Where this fits in Lilly's retatrutide programme
This is not the first retatrutide Phase 3 readout. Lilly has previously reported that the TRIUMPH-1 trial in adults with obesity but without diabetes reported an average weight loss of 28.3% on the 12 mg dose at 80 weeks, and TRIUMPH-2 in people with both type 2 diabetes and obesity reported 20.8%. A further trial, TRIUMPH-5, is comparing retatrutide directly with Lilly's own tirzepatide. Lilly has not given a date for regulatory submissions.
Kenneth Custer, president of Lilly Cardiometabolic Health, said head-to-head trials show patients and doctors how a new medicine compares with existing treatment, and that retatrutide could change how type 2 diabetes and obesity are treated if it is approved.
5. What it means for Ireland
For Irish patients, nothing changes yet. Retatrutide would need a European marketing authorisation, followed by an HSE pricing and reimbursement assessment, before it could be prescribed under public schemes. That process is already slow for the drugs on the market: as we reported, the HSE is still weighing public funding for Mounjaro for weight management, with the National Centre for Pharmacoeconomics flagging the budget impact.
The industrial link is stronger. Lilly's campus in Kinsale, Co Cork, makes the active ingredient for tirzepatide, and in September 2024 the company announced about USD 1.8 billion of further investment in its Irish sites, roughly USD 800 million in Kinsale and USD 1 billion in its new Limerick facility. Lilly has not said where retatrutide would be manufactured.
Frequently Asked Questions
Is retatrutide available in Ireland?
No. It is an investigational medicine and has not been approved by the European Medicines Agency, the FDA or any other regulator. It is only available inside clinical trials.
Did retatrutide really double the weight loss of Ozempic?
In this trial, average weight loss was 20.9% on retatrutide 12 mg against 9.4% on semaglutide 2 mg, a little more than double. The trial involved people with type 2 diabetes, who usually lose less weight on these drugs than people without diabetes.
When will the full results be published?
Lilly says the detailed results will be presented at a future medical meeting and published in a peer-reviewed journal. No date has been given.
Should I change my diabetes or weight-loss medicine?
No. This article reports trial results and is not medical advice. Anyone on a GLP-1 medicine should talk to their GP or specialist before making any change.
Outlook
TRANSCEND-T2D-2 gives the first direct comparison between retatrutide and the most widely known weight-loss injection, and the gap on weight is large. The higher discontinuation rate on the top dose, the open-label design and the lack of peer-reviewed data are the main caveats. The next milestones to watch are the full publication, the TRIUMPH-5 comparison with tirzepatide and Lilly's filing plans in the US and Europe.
Sources
- AJMC, Retatrutide tops semaglutide on A1C, weight in head-to-head trial, 28 October 2026
- HCPLive, TRANSCEND-T2D-2: retatrutide beats semaglutide 2 mg on A1C, weight loss, 28 October 2026
- ClinicalTrials.gov, NCT06260722
- RTÉ Radio 1, News at One, 29 October 2026
- Fierce Pharma, Eli Lilly reveals USD 1.8B in investments at Irish manufacturing sites, September 2024
Cover image: Eli Lilly and Company Corporate Center, Indianapolis, Paul Sableman, CC BY 2.0, via Wikimedia Commons.
