Lilly says retatrutide met goals in two more Phase 3 trials, with FDA filing set for early 2027

Eli Lilly reported on July 23, 2026 that retatrutide, its experimental once-weekly weight-loss drug, met the main goal of two more Phase 3 trials, and said it plans to ask the FDA to approve the medicine in the first quarter of 2027 ^[1][2]. Retatrutide is investigational and cannot legally be sold or marketed for human use ^[1]. Lilly already sells Zepbound (tirzepatide) and Foundayo (orforglipron) ^[1].

In TRIUMPH-2, 1,152 adults with type 2 diabetes and obesity or overweight were assigned at random to retatrutide 4 mg, 9 mg, 12 mg, or placebo for 80 weeks ^[1][2]. Average weight loss was 12.7% (29.8 lbs) at 4 mg, 19.1% (45.4 lbs) at 9 mg and 20.8% (49.6 lbs) at 12 mg, compared with 4.0% (9.3 lbs) on placebo ^[1][2]. Participants started at an average of 234.6 lbs and a BMI of 38.2 ^[1]. A1C, a measure of average blood sugar, fell from a starting average of 7.7% by 1.4 points at 4 mg, 1.6 points at 9 mg and 1.5 points at 12 mg, versus 0.2 points on placebo ^[1].

TRIUMPH-3 enrolled 1,949 adults with severe obesity, defined as a BMI of 35 or higher, and established cardiovascular disease, with or without type 2 diabetes ^[1]. Weight loss averaged 21.6% (52.7 lbs) at 9 mg and 22.6% (55.8 lbs) at 12 mg over 80 weeks, versus 3.2% (7.7 lbs) on placebo ^[1][2]. On heart-related events, there were 44 MACE-5 events (death from any cause, heart attack, stroke, heart failure event or coronary revascularization) among participants assigned to retatrutide and 52 among those on placebo, a hazard ratio of 0.82 with a 95% confidence interval of 0.55 to 1.22 ^[1]. For MACE-3 (cardiovascular death, heart attack or stroke), there were 27 events with retatrutide and 23 with placebo, a hazard ratio of 1.12 (0.64 to 1.96) ^[1]. Both ranges cross 1.0, meaning the trial did not establish a difference in cardiovascular risk in either direction. Lilly said these events occurred less often than anticipated in both groups ^[1].

At 12 mg, TRIUMPH-3 participants averaged reductions of 37.0% in triglycerides, 16.5% in non-HDL cholesterol, 9.3 mmHg in systolic blood pressure and 51.2% in high-sensitivity C-reactive protein, a marker of inflammation ^[1]. Side effects were mostly gastrointestinal. In TRIUMPH-2, diarrhea was reported by 27.4%, 33.5% and 33.6% of the 4 mg, 9 mg and 12 mg groups versus 13.2% on placebo, and nausea by 13.7%, 20.8% and 28.0% versus 8.0% ^[1]. Discontinuations because of side effects in TRIUMPH-3 were 9.8% at 9 mg and 13.5% at 12 mg, compared with 4.8% on placebo; in TRIUMPH-2 they were 3.8% at 4 mg, 11.6% at 9 mg and 7.7% at 12 mg, compared with 4.9% on placebo ^[1].

Lilly said it is completing the Chemistry, Manufacturing and Controls data package required for a Biologics License Application and intends to submit in the first quarter of 2027 ^[1]. Its second-quarter results, released August 5, 2026, said the clinical data package is complete for global registrations in obesity, obstructive sleep apnea and knee osteoarthritis pain ^[4]. The application type is contested: the FDA determined retatrutide is neither a protein nor a biological product, a district court vacated that designation and returned the question to the agency, and Lilly has appealed ^[3]. The choice affects how long market exclusivity would run, 12 years versus five ^[3].

Why it matters for patients

Retatrutide is not available now and will not be unless the FDA approves it. A first-quarter 2027 filing would start a review, not end one, and no FDA decision date has been disclosed ^[1][3]. People taking semaglutide (Ozempic, Wegovy, Rybelsus), tirzepatide (Mounjaro, Zepbound) or orforglipron (Foundayo) are using approved medicines; retatrutide is a different molecule that acts on three hormone receptors rather than one or two ^[1]. Weight-loss percentages from different trials are not directly comparable, because the studies enroll different patients for different lengths of time ^[3]. The TRIUMPH figures are averages using the efficacy estimand, which assumes all participants stayed on their assigned treatment without starting other weight-management medicines ^[1]. Higher doses produced more weight loss and also more gastrointestinal side effects and more discontinuations ^[1]. Lilly has brought six U.S. lawsuits against sellers of unapproved retatrutide, which remains investigational ^[3].

What happens next

• Lilly plans to submit a Biologics License Application to the FDA in the first quarter of 2027 ^[1][4].
• Full TRIUMPH-2 and TRIUMPH-3 results will be presented at future medical meetings and published in peer-reviewed journals; no dates have been given ^[1].
• The Seventh Circuit hears oral arguments in Lilly's appeal over the application type on September 24, 2026 ^[3].
• Further readouts from the TRIUMPH program are expected before the end of 2026 ^[3].