Retatrutide wins two more Phase 3 trials and Lilly sets a Q1 2027 FDA filing

Eli Lilly announced on July 23, 2026 that retatrutide, an experimental once-weekly injection that acts on three hormone receptors, succeeded in two more Phase 3 trials ^[1]. The company also said it plans to submit a Biologics License Application to the US Food and Drug Administration in the first quarter of 2027 ^[1].

Retatrutide is not approved anywhere and cannot legally be sold for human use ^[1]. It activates receptors for GIP, GLP-1 and glucagon — one more target than tirzepatide (Mounjaro and Zepbound), which hits GIP and GLP-1 ^[1].

What the two trials found

TRIUMPH-2 enrolled 1,152 adults with type 2 diabetes plus obesity or overweight and randomized them to retatrutide 4 mg, 9 mg, 12 mg or placebo for 80 weeks ^[1]. Average starting weight was 234.6 lbs, with an average BMI of 38.2 ^[1]. On the efficacy estimand — which models what would have happened if everyone stayed on treatment — participants lost an average of 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, versus 4.0% (9.3 lbs) on placebo ^[1]. A1C fell by 1.4, 1.6 and 1.5 percentage points from a baseline of 7.7%, compared with 0.2 points on placebo ^[1].

TRIUMPH-3 enrolled 1,949 adults with severe obesity (BMI of 35 or higher) and established cardiovascular disease, with or without type 2 diabetes ^[1]. Average baseline weight was 245.6 lbs and average BMI was 40.4 ^[1]. At 80 weeks, weight loss averaged 21.6% (52.7 lbs) at 9 mg and 22.6% (55.8 lbs) at 12 mg, versus 3.2% (7.7 lbs) on placebo ^[1].

TRIUMPH-3 also tracked heart events, but Lilly said they occurred less often than expected in both groups ^[1]. For the broader MACE-5 measure (death from any cause, heart attack, stroke, heart failure event or coronary revascularization), there were 44 events on retatrutide and 52 on placebo, a hazard ratio of 0.82 with a confidence interval of 0.55 to 1.22 ^[1]. For the narrower MACE-3 measure, there were 27 events on retatrutide and 23 on placebo, a hazard ratio of 1.12 (0.64 to 1.96) ^[1]. Both intervals cross 1.0, meaning the trial did not establish a heart benefit or harm. At the highest dose, the drug cut triglycerides by an average of 37.0%, non-HDL cholesterol by 16.5%, systolic blood pressure by 9.3 mmHg, waist circumference by 7.5 inches and hsCRP by 51.2% ^[1].

Side effects

Digestive problems dominated. In TRIUMPH-2, diarrhea affected up to 33.6% of retatrutide users versus 13.2% on placebo, nausea up to 28.0% versus 8.0%, and vomiting up to 15.7% versus 4.2% ^[1]. In TRIUMPH-3, diarrhea reached 30.1% versus 8.7% ^[1]. Dysesthesia — abnormal skin sensations such as burning or tingling — occurred in up to 7.3% of retatrutide users in TRIUMPH-2 versus 0.7% on placebo, and 6.4% versus 1.3% in TRIUMPH-3 ^[1]. Lilly said these events were generally mild to moderate and mostly resolved during treatment ^[1].

Dropouts due to side effects were notable. In TRIUMPH-2 they were 3.8% (4 mg), 11.6% (9 mg) and 7.7% (12 mg) versus 4.9% on placebo; in TRIUMPH-3, 9.8% and 13.5% versus 4.8% ^[1].

Why it matters for patients

These are topline numbers from a company press release, not peer-reviewed publications; Lilly said detailed results will be presented at medical meetings later ^[1]. Cross-trial comparisons are unreliable because study lengths and patient populations differ ^[3].

The more immediate point is timing. Retatrutide will not be an option in US pharmacies for a while. Lilly said it is still completing the Chemistry, Manufacturing, and Controls data package required for a BLA and will file after that, in the first quarter of 2027 ^[1]. Regulatory review then takes additional months. The sources provided do not state what earlier filing date, if any, Lilly had previously given.

There is also an unusual legal wrinkle. Lilly intends to file a Biologics License Application rather than a New Drug Application, but that classification is tied up in litigation with the FDA, which determined retatrutide is neither a protein nor a biological product ^[3]. A district court vacated that designation and sent the broader question back to the agency; Lilly has appealed ^[3]. The stakes include exclusivity — twelve years versus five ^[3].

Because the drug is investigational, anything sold online as retatrutide is unapproved. Lilly has brought six US lawsuits against sellers of unapproved retatrutide ^[3].

What happens next

Lilly confirmed on August 5, 2026 that the retatrutide clinical data package is complete, supporting registrations in obesity, obstructive sleep apnea and knee osteoarthritis pain ^[4][3]. The Seventh Circuit was scheduled to hear oral arguments in Lilly's appeal against the FDA on September 24, 2026 ^[3]. The BLA submission is targeted for the first quarter of 2027 ^[1][4].