Lilly's retatrutide beats Ozempic on blood sugar and doubles its weight loss in Phase 3

Eli Lilly said on 28 October 2026 that retatrutide, its once-weekly triple hormone receptor agonist, outperformed Novo Nordisk's Ozempic 2 mg on both A1C and body weight over 80 weeks in TRANSCEND-T2D-2, the first Phase 3 trial to pit the drug against another incretin medicine¹. The results are topline figures from a company announcement and have not yet been published in a peer-reviewed journal¹.

What the trial found

TRANSCEND-T2D-2 was a randomised, open-label study of 1,298 adults whose type 2 diabetes was not controlled on metformin, with or without an SGLT2 inhibitor¹. Participants entered with an A1C of 7.0% to 10.5% and were assigned 2:2:1 to retatrutide 9 mg, retatrutide 12 mg or Ozempic 2 mg, which is the highest approved dose of Novo's drug¹. The primary objective was to show that the 12 mg dose was noninferior to Ozempic on A1C at 80 weeks¹.

Both retatrutide doses cut A1C by an average of 2.2% from a baseline of 8.3%, against 1.8% for Ozempic¹. Fierce Biotech reported that the difference was statistically significant and met the primary endpoint². Weight fell by 19.5% (20.1 kg) on the 9 mg dose and 20.9% (21.5 kg) on 12 mg, compared with 9.4% (9.5 kg) on Ozempic, from an average starting weight of 102.4 kg¹. Lilly also reported larger improvements than Ozempic in non-HDL cholesterol, triglycerides and systolic blood pressure, without giving figures¹.

The tolerability picture is less one-sided. Diarrhoea affected 28.3% and 32.7% of patients on the two retatrutide doses against 26.4% on Ozempic, and vomiting 10.2% and 15.0% against 13.2%¹. Constipation was more common on Ozempic, at 19.8% against 14.2% and 13.1%¹. Dysesthesia occurred in 4.8% and 6.5% of retatrutide patients against 2.7% on Ozempic¹. Discontinuation because of adverse events reached 7.9% on the 12 mg dose, nearly three times the 2.7% seen with Ozempic¹².

Kenneth Custer, president of Lilly Cardiometabolic Health, framed the design around prescribing decisions: "Head-to-head trials show patients and physicians how a potential new medicine compares with treatments that are available and reimbursed today."¹

What it means for the market

The readout strengthens Lilly's hand in a category it already leads. Tirzepatide, sold as Mounjaro and Zepbound, brought in $27.7 billion of Lilly's $42.8 billion revenue in the first half of this year, pharmaphorum reported³. The same report cited analyst forecasts of $10 billion to $25 billion a year in peak sales for retatrutide, and described Novo's efforts to follow semaglutide with candidates such as CagriSema as less impressive³.

For payers and health systems, direct comparative data against a reimbursed standard of care is the evidence that tends to shape formulary and value assessments, and TRANSCEND-T2D-2 is the sixth Phase 3 trial in which retatrutide has hit its goals¹³. Lilly plans to file for FDA approval in the first quarter of 2027, according to Fierce Biotech². The comparison that matters most commercially, retatrutide against Lilly's own tirzepatide, is still running in the TRIUMPH-5 trial in adults with obesity¹.

Caveats

All figures Lilly released are for the efficacy estimand, which models results as if every randomised participant had stayed on treatment for the full 80 weeks without adding other glucose-lowering drugs¹. Results counting everyone who started the trial have not been disclosed. The study was open-label, and superiority of the 9 mg dose on A1C showed only nominal statistical significance rather than being controlled for multiple comparisons¹. Retatrutide is not approved by any regulator¹. Lilly says detailed results will be presented at a future medical meeting and published in a peer-reviewed journal, and around 650 participants are continuing on retatrutide for a further 24 weeks in an extension to assess longer-term efficacy and safety¹.