Lilly’s retatrutide trounces Novo’s Ozempic in diabetes, weight loss

News Drug Development Lilly’s retatrutide trounces Novo’s Ozempic in diabetes, weight loss October 28, 2026 | 3 min read | Annalee Armstrong Twitter LinkedIn Facebook Email Print Eli Lilly’s next-gen weight loss drug retatrutide soundly beat Novo’s approved medicine Ozempic in weight loss and blood sugar reduction, padding the case for a regulatory application that’s expected in the first quarter of 2027. Eli Lilly’s highly anticipated obesity drug retatrutide—heralded as the strongest weight loss medicine so far—has beaten rival Novo’s Ozempic in a head-to-head Phase 3 test in weight loss and blood sugar reduction, giving doctors a direct comparison as they sort through the many options now, or soon to be, available to them.In the TRANSCEND-T2D-2 study, both doses of retatrutide—9 mg and 12 mg—reduced average blood sugar (A1C) by 2.2% as compared to 1.8% for Ozempic 2 mg at 80 weeks, Lilly announced Wednesday. As for weight loss, patients taking Lilly’s drug lost an average of 44–47 pounds, representing about 20% of body weight, compared to 21 pounds, or 9%, with Novo’s approved diabetes option.The study tested the two doses of once-weekly retatrutide in 1,298 adults with type 2 diabetes inadequately controlled with metformin, with or without an SGLT2 inhibitor.

The main goal of the trial was to show that retatrutide was at least as good as Ozempic in reducing A1C, a measurement of average blood glucose over 2–3 months that is a key biomarker for diabetes. Weight loss served as a key secondary goal. But while retatrutide had the efficacy edge, the next-gen candidate had a higher rate of adverse events than Ozempic.

Lilly reported that 32.7% and 28.3% of patients on the high and low dose, respectively, experienced diarrhea compared with 26.4% for Ozempic. There was also a higher incidence of dysesthesia, a neurological symptom that causes a prickling or burning sensation. The rate of dysesthesia was 4.8% and 6.5% for the low and high doses of retatrutide and 2.7% for Ozempic.Still, the achievement marks the sixth clinical win for retatrutide, Lilly said in its release.

And it was the first time retatrutide was compared head-to-head with another incretin product in a Phase 3 study, according to Kenneth Custer, executive VP and president of Lilly Cardiometabolic Health.Head-to-head trials are a bold bet from a pharma company, typically reserved for approved medicines to show superiority over rivals. Lilly and Novo have been performing more of these trials as they fight neck-and-neck for dominance of the lucrative obesity and diabetes markets. Obesity Lilly preps FDA run for ‘triple-G’ weight loss drug with Phase 3 data With weight loss topping 20% at 80 weeks in the Phase 3 TRIUMPH-2 and TRIUMPH-3 trials, Eli Lilly plans to file for retatrutide’s approval in the first quarter of 2027.

Previously a filing was expected later this year. July 23, 2026 · 3 min read · Tristan Manalac Read more “Head-to-head trials show patients and physicians how a potential new medicine compares with treatments that are available and reimbursed today,” Custer said in a statement. “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.”Retatrutide has generated significant buzz as it nears the market, as well as a black- market for the drug, which is not yet approved anywhere.

The Phase 3 TRANSCEND-T2D program, which has enrolled more than 2,050 patients, is helping Lilly build a case for regulators. Lilly previously reported results from the Phase 3 TRANSCEND-T2D-1 study showing that retatrutide beat placebo at reducing A1C, with an average reduction of 1.7%–2% over 40 weeks compared to a 0.8% average drop for placebo comparators. The drug also elicited weight loss of 16.8% at this timepoint, while placebo comparators saw 2.5% weight loss.Lilly promised to present more from the TRANSCEND-T2D-2 trial at an upcoming medical meeting.

Retatrutide is the anchor of Lilly’s up-and-coming weight loss portfolio. The injectable triple hormone receptor agonist helps activate the body’s receptors for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon. The company, which boasts a market cap of $1 trillion thanks to its obesity and diabetes portfolio, has previously announced plans to file retatrutide for FDA approval in the first quarter of 2027.Lilly is examining the drug for a range of conditions that occur with diabetes and obesity, including knee osteoarthritis pain, moderate-to-severe obstructive sleep apnea, chronic low back pain, cardiovascular outcomes and metabolic dysfunction-associated steatotic liver disease.

Regulatory Lilly, FDA retatrutide biologic dispute comes to a head as submission nears A legal dispute between the FDA and Eli Lilly over whether the highly anticipated obesity candidate retatrutide is indeed a biologic has come to a head as the company prepares to submit the medicine for approval. August 5, 2026 · 3 min read · Annalee Armstrong Read more Twitter LinkedIn Facebook Email Print Obesity Diabetes Weight loss Metabolic disorders Eli Lilly and Company Novo Annalee Armstrong Annalee Armstrong is an award-winning biopharma journalist covering the business of drug development. She has been a journalist for more than 18 years, covering the pharmaceutical and biotech industry for the last eight.

She is senior editor at BioSpace and curates the Biopharm Executive newsletter every Wednesday. You can reach her at annalee.armstrong@biospace.com. Follow her on LinkedIn.