Lilly Says Retatrutide Beat Ozempic 2 mg on Weight Loss and A1C in Head-to-Head Diabetes Trial

Eli Lilly says its experimental injection retatrutide delivered more than double the weight loss of Novo Nordisk's Ozempic in a head-to-head trial of adults with type 2 diabetes. The company announced the topline results this morning, Oct. 28, at 6:45 a.m. ET.

The trial is called TRANSCEND-T2D-2. Lilly says retatrutide met the primary endpoint and every key secondary endpoint at 80 weeks.

The numbers

Participants started with an average A1C of 8.3% and an average weight of 102.4 kg (225.8 lbs). Both retatrutide doses, 9 mg and 12 mg, lowered A1C by an average of 2.2%. Ozempic 2 mg lowered it by 1.8%.

The weight gap is larger:

• Retatrutide 9 mg: 19.5% body weight loss, or 44.3 lbs
• Retatrutide 12 mg: 20.9%, or 47.4 lbs
• Ozempic 2 mg: 9.4%, or 20.9 lbs

Lilly also reported bigger improvements for retatrutide in non-HDL cholesterol, triglycerides and systolic blood pressure. Lilly picked Ozempic 2 mg as the comparator because it is the highest approved Ozempic dose.

"Head-to-head trials show patients and physicians how a potential new medicine compares with treatments that are available and reimbursed today," said Kenneth Custer, president of Lilly Cardiometabolic Health. He added that retatrutide, "if approved, could shift the treatment paradigm for people living with type 2 diabetes, obesity and related cardiometabolic conditions."

Side effects

Lilly's release lists the most common adverse events for retatrutide at 9 mg and 12 mg against Ozempic:

• Diarrhea: 28.3% and 32.7% vs. 26.4%
• Nausea: 21.2% and 23.8% vs. 21.3%
• Constipation: 14.2% and 13.1% vs. 19.8%
• Vomiting: 10.2% and 15.0% vs. 13.2%

Business Insider reported that retatrutide patients also had slightly higher rates of dysesthesia, a rare side effect that causes tingling or burning skin sensations.

What retatrutide is, and what it is not yet

Retatrutide is a once-weekly injection that activates three hormone receptors: GLP-1, GIP and glucagon. That earns it the nickname "triple G." Ozempic targets GLP-1 alone. Lilly's own Mounjaro and Zepbound, both tirzepatide, hit GLP-1 and GIP.

These are company-announced topline results. Business Insider reported they have not been peer-reviewed or published in a medical journal. Retatrutide has no FDA approval.

Lilly has said it hopes to file for approval early next year. The company says TRANSCEND-T2D-2 is the sixth Phase 3 trial in which retatrutide has shown strong efficacy, and the first to compare it directly with another incretin drug. Lilly is also running TRIUMPH-5, which pits retatrutide against tirzepatide in adults with obesity.

Sleep apnea data

Separate research in The New England Journal of Medicine looked at retatrutide in obstructive sleep apnea. Two randomized Phase 3 trials enrolled 691 adults with moderate-to-severe apnea and a BMI of at least 27. Of those, 243 did not have type 2 diabetes and 448 did.

Participants lost between 12% and nearly 20% of body weight over 80 weeks. About 68% saw an improvement of more than 50% in apnea severity, with or without diabetes. Hypoxic burden, the severity and duration of low-oxygen episodes during sleep, fell about 75% in patients without diabetes and 65% in those with it.

The researchers listed the drug's lack of FDA approval as a limitation. They said further study is needed on long-term cardiovascular effects.

The gray market

The FDA has warned that unauthorized versions of retatrutide are being illegally marketed and sold online for weight loss. Business Insider reported that overseas sellers are shipping powders labeled "reta," feeding a do-it-yourself injection market among bodybuilders. The long-term safety of that use is unknown, and the drug is still in clinical trials.

Money and management

Tirzepatide contributed $27.7 billion of Lilly's $42.8 billion in first-half 2026 revenue, about two-thirds of the total, according to pharmaphorum. Analyst forecasts cited by pharmaphorum put retatrutide's peak sales at $10 billion to $25 billion a year. Those are estimates, not results.

Lilly is also reorganizing. Patrik Jonsson, president of Lilly International, retires at the end of this year after 36 years with the company. Lilly is merging its U.S. and international divisions into Lilly Global Markets under Ilya Yuffa, with Laura Steele named president of Lilly USA. CEO David Ricks said "now is the right time to consolidate our geographies for greater impact."

Lilly reports quarterly earnings Thursday, Oct. 29, according to Business Insider. The full TRANSCEND-T2D-2 data have not yet been published, so peer-reviewed numbers and a complete safety picture are still to come before the early-2027 filing.