Lilly’s triple-G drug hits 22.6% weight loss, but impact on reducing cardio risk is less clear

Biotech Lilly’s triple-G drug hits 22.6% weight loss, but impact on reducing cardio risk is less clear By James Waldron Jul 23, 2026 9:06am Eli Lilly Obesity weight loss Clinical Data Eli Lilly’s triple-G drug retatrutide has hit the primary endpoints of a pair of phase 3 obesity trials, although the peak weight loss fell short of previous trials in different patient populations while failing to prove the medication reduces cardiovascular risk The pharma evaluated various doses of the GIP, GLP-1 and glucagon triple hormone receptor agonist against placebo in both the TRIUMPH-2 study of 1,152 patients with type 2 diabetes and obesity or overweight, as well as the TRIUMPH-3 study of 1,949 patients with severe obesity and established cardiovascular disease. When looking at the efficacy estimand—which assesses data based on patients who stayed on the trial regimen without starting other “prohibited” weight loss treatments—patients in TRIUMPH-2 receiving the 12 mg dose of retatrutide saw 20.8% weight loss at 80 weeks, compared to 3.2% among the placebo cohort. In TRIUMPH-3, patients on the 12 mg dose experienced an average of 22.6% weight loss at the same timepoint, compared to 3.2% for the placebo group. These results hit the studies’ primary endpoints. However, they came in below the TRIUMPH-4 study in December, which showed 28.7% weight loss at 68 weeks in patients with obesity and knee osteoarthritis. The weight loss for the TRIUMPH-1 study in May was similar, reaching 28.3% after 80 weeks. Admittedly, those studies didn’t include patients with diabetes, who can often see a lower level of weight loss. While Citi analysts acknowledged in May that the TRIUMPH-1 readout “nominally clear[ed]” Wall Street’s placebo-adjusted expectation of 25%, they suggested the result fell short of some expectations. This morning's data also showed that a total of 7.7% of patients in TRIUMPH-2 discontinued treatment due to adverse events —rising to 11.6% for those on 9 mg—while 13.5% of patients in the 12 mg cohort of TRIUMPH-3 discontinued their treatment. This was slightly higher than the 11.3% of patients who discontinued treatment inTRIUMPH-1, which analysts at the time praised as a “significantly improved” result. Gastrointestinal side effects are a common issue with GLP-1 drugs. Diarrhea affected 33.6% of patients on the highest retatrutide dose in TRIUMPH-2 and 24.4% of those in TRIUMPH-3. For nausea, the figures were 38% and 22.4%, respectively, while constipation was 16.8% and 15.7%. TRIUMPH-3 also assessed retatrutide’s impact on reducing cardiovascular events, and here the results were less clear-cut. There were 44 major adverse cardiovascular events—ranging from death and heart attack to coronary revascularization—across both retatrutide cohorts, compared to 52 events in the placebo group. Lilly blamed this lack of differentiation on the fact that these major adverse cardiovascular events “occurred less frequently than anticipated in both retatrutide and placebo arms.” It was better news when it came to reducing cardiovascular risk factors, with the 12 mg dose delivering average reductions in triglycerides, non-HDL cholesterol and high-sensitivity C-reactive protein of 37%, 16.5% and 51.2%, respectively. “Across five positive phase 3 studies, retatrutide has shown powerful efficacy, and we believe it could be an important future tool in the management of cardiometabolic health,” Kenneth Custer, Ph.D., president of Lilly Cardiometabolic Health, said in the July 23 release. “With the positive results from TRIUMPH-2 and TRIUMPH-3, we now have the clinical data package to support global submissions for retatrutide as a potential treatment for obesity, knee osteoarthritis pain and obstructive sleep apnea,” Custer added. “We look forward to working with regulators as they evaluate this first-of-its-kind medicine.” Lilly plans to submit retatrutide to the FDA in the first quarter of 2027, although Citi analysts have previously pointed to the drug as a more niche market opportunity for Lilly. This view reflects the monumental sales of Lilly’s existing obesity drugs, with retatrutide's $6.6 billion peak consensus sales estimate still considered large by most measures. William Blair analysts said retatrutide's weight loss magnitude “shined again” in this morning's readout. “Taken together, we believe retatrutide is positioned well within the ultra-high potency category of anti-obesity medications,” the analysts said. “However, given the tolerability profile, it will likely be limited to individuals at the higher end of the BMI spectrum, where the benefit-risk calculus is more favorable.” Eli Lilly Obesity weight loss Clinical Data Biotech