Lilly's retatrutide shows weight, A1C, knee pain and sleep apnea benefits in late-stage trials

Eli Lilly said June 6, 2026, that its experimental once-weekly drug retatrutide produced substantial weight loss and also improved blood sugar control, knee osteoarthritis pain and obstructive sleep apnea in two Phase 3 trials. The results were presented at the American Diabetes Association's 86th Scientific Sessions, held in New Orleans, and the type 2 diabetes trial was published at the same time in The Lancet ^[1][2]. Retatrutide is an investigational drug that activates three hormone receptors — GIP, GLP-1 and glucagon — and is legally available only to participants in Lilly's clinical trials ^[1][2].

What the trials found

TRIUMPH-1 enrolled 2,339 adults with obesity or overweight, randomly assigned to retatrutide 4 mg, 9 mg or 12 mg or to placebo for 80 weeks ^[1]. Average weight loss was 47.2 lbs (19.0%) at 4 mg, 64.4 lbs (25.9%) at 9 mg and 70.3 lbs (28.3%) at 12 mg ^[1]. Among participants on 12 mg, 65.3% finished below the BMI 30 threshold for obesity and 33.3% reached a BMI under 25 ^[1]. In a pre-specified extension, 532 participants whose BMI was at least 35 at the start and who stayed on 12 mg lost an average of 85.0 lbs (30.3%) by 104 weeks ^[1].

Two smaller trials nested inside TRIUMPH-1 looked at specific complications ^[1]. In adults with knee osteoarthritis, retatrutide reduced WOMAC pain scores by up to 4.3 points, or 73.1%, from a baseline of 6.0 on a 0–10 scale where higher scores mean worse symptoms ^[1]. In adults with moderate-to-severe obstructive sleep apnea, the apnea-hypopnea index fell by up to 36.1 events per hour, or 60.6%, from a baseline of 58.6 events per hour ^[1]. Reuters noted that Zepbound, Lilly's tirzepatide, is already approved for obstructive sleep apnea ^[2].

TRANSCEND-T2D-1 enrolled 537 adults with type 2 diabetes who were not taking other diabetes medicines ^[1]. At 40 weeks, A1C fell by up to 2.0 percentage points from a baseline of 7.9%; up to 90% of participants reached an A1C below 7.0%, up to 85% reached 6.5% or below, and up to 46% reached below 5.7%, the threshold for normal blood sugar ^[1]. Participants on 12 mg lost an average of 36.6 lbs (16.8%), and weight loss had not yet plateaued at 40 weeks ^[1].

Side effects were common. In TRIUMPH-1, the most frequent were nausea (up to 42.4%, versus 14.8% on placebo), diarrhea (up to 34.1%, versus 13.5%), constipation (up to 26.1%, versus 10.9%) and vomiting (up to 25.3%, versus 4.8%) ^[1]. Dysesthesia — abnormal touch or tingling sensations — was reported by 5.1%, 12.3% and 12.5% of participants at 4 mg, 9 mg and 12 mg, versus 0.9% on placebo; Lilly said these events were generally mild to moderate, most resolved during treatment, and most participants stayed on the drug ^[1]. Discontinuation because of side effects was 4.1%, 6.9% and 11.3% at 4 mg, 9 mg and 12 mg, versus 4.9% on placebo ^[1]. In TRANSCEND-T2D-1, nausea reached 26.5% versus 3.7% on placebo, diarrhea 26.3% versus 4.5%, and vomiting 17.6% versus 2.2%; discontinuation due to side effects was 5.1% at 12 mg versus 0.0% on placebo ^[1].

Reuters reported that in one of the studies, 2% of patients with diabetes who took the lowest dose experienced major adverse cardiovascular events, which were not necessarily caused by the drug, according to the Lancet paper ^[2].

Why it matters for patients

Retatrutide is not approved for any use, and it cannot be prescribed. The trial results suggest that one medicine might eventually address several conditions that are usually treated separately. For people now taking semaglutide (Ozempic, Wegovy, Rybelsus) or tirzepatide (Mounjaro, Zepbound), nothing changes today: those drugs have their own approved uses and their own safety labeling.

The trials compared retatrutide only with placebo. It was not tested head-to-head against semaglutide or tirzepatide, so how it stacks up against approved options has not been reported ^[1][2]. The side-effect profile was generally consistent with trials of other incretin-based therapies, Lilly said ^[1]. Whether the knee pain and sleep apnea benefits hold up in broader groups of patients, and what happens after people stop the drug, has not been reported.

What happens next

Lilly is studying retatrutide in additional Phase 3 trials, including chronic low back pain, cardiovascular and renal outcomes, and metabolic dysfunction-associated steatotic liver disease ^[1]. The TRIUMPH program, which began in 2023, has enrolled more than 5,800 participants; the TRANSCEND-T2D program, which began in 2024, has enrolled more than 2,050, with more results expected over the next year ^[1]. Lilly has not disclosed a date for a regulatory submission or decision ^[1][2].