TRIUMPH-1 retatrutide topline raises the ceiling above tirzepatide's trial numbers

Eli Lilly reported topline results on May 21, 2026, from TRIUMPH-1, a Phase 3 trial of retatrutide, an investigational once-weekly injection that activates three hormone receptors: GIP, GLP-1 and glucagon ^[1]. In adults with obesity or overweight plus at least one weight-related condition and without diabetes, all three doses met the trial's primary and key secondary endpoints at 80 weeks ^[1].

The trial randomized 2,339 participants 1:1:1:1 to retatrutide 4 mg, 9 mg, 12 mg or placebo ^[1]. Average starting weight was 112.7 kg (248.5 lbs), with an average BMI of 40.0 ^[1]. On the efficacy estimand — which models what would have happened if everyone stayed on treatment — average weight change at 80 weeks was −19.0% (47.2 lbs) at 4 mg, −25.9% (64.4 lbs) at 9 mg and −28.3% (70.3 lbs) at 12 mg, versus −2.2% (5.5 lbs) with placebo ^[1]. On the treatment-regimen estimand, which counts people regardless of whether they stuck with the drug, the figures were −17.6%, −23.7% and −25.0% versus −3.9% for placebo ^[1].

Thresholds tell a similar story. At 12 mg, 62.5% lost at least 25% of body weight, 45.3% lost at least 30%, and 27.2% lost at least 35%, compared with 2.2%, 0.5% and 0.3% on placebo ^[1]. Lilly also said 65.3% of the 12 mg group reached a BMI under 30 at 80 weeks, including 37.5% of those who began with a BMI of 40 or higher, though that second figure was a post-hoc analysis ^[1]. Waist circumference fell 24.1 cm (9.5 inches) at 12 mg versus 3.6 cm with placebo ^[1].

A pre-specified blinded extension enrolled 532 participants with a baseline BMI of 35 or higher who finished the 80-week study on their assigned dose; they continued 24 more weeks with escalation to a maximum tolerated dose of 9 mg or 12 mg ^[1]. In that group, the 12 mg arm reached −30.3% (85.0 lbs) at 104 weeks on the efficacy estimand, and people who had been on placebo lost 19.2% after switching ^[1].

Side effects rose with dose

The most common adverse events at 12 mg were nausea (42.4% vs 14.8% placebo), diarrhea (32.0% vs 13.5%), constipation (26.1% vs 10.9%) and vomiting (25.3% vs 4.8%) ^[1]. Dysesthesia — an unpleasant nerve sensation — occurred in 5.1%, 12.3% and 12.5% at 4, 9 and 12 mg versus 0.9% with placebo, and urinary tract infections in 7.5%, 8.8% and 8.4% versus 5.3% ^[1]. Lilly said these events were generally mild to moderate and most resolved during treatment ^[1]. Discontinuation because of adverse events was 4.1% at 4 mg, 6.9% at 9 mg and 11.3% at 12 mg, compared with 4.9% on placebo ^[1]. Lilly's Dan Skovronsky told CNBC the company did not observe cardiac or liver issues, a question analysts had raised because glucagon increases energy expenditure ^[4].

Why it matters for patients

Retatrutide is not approved and is legally available only through Lilly's clinical trials ^[1]. Nothing in these results changes what is on pharmacy shelves today.

Still, the numbers reset expectations. CNBC reported that analysts had been looking for weight loss above tirzepatide's roughly 20% to 22% in Zepbound trials ^[4]. The 4 mg dose, reached with a single escalation step, produced 19.0% average loss with a discontinuation rate below placebo ^[1], which Skovronsky said was similar to high-dose Zepbound with better tolerability ^[4]. That suggests future choices may involve trading efficacy against side-effect burden rather than simply going to the highest dose. Lilly has also registered a head-to-head study comparing retatrutide with tirzepatide in adults with obesity ^[2].

One caveat: the two estimands differ by roughly 3 percentage points at 12 mg — 28.3% versus 25.0% ^[1] — and the real-world figure usually tracks closer to the treatment-regimen number. CNBC described the trial as having about 2,500 patients ^[4], while Lilly's release specifies 2,339 randomized ^[1].

What happens next

More TRIUMPH-1 data will be presented at the 86th American Diabetes Association Scientific Sessions, with results from TRIUMPH-2 (type 2 diabetes) and TRIUMPH-3 (established cardiovascular disease) expected later in the year ^[1]. Analyses of the knee osteoarthritis and sleep apnea basket trials will come separately ^[1]. A filing or approval timeline has not been announced ^[1][4].