Eli Lilly's Retatrutide Posts Record 25% Weight Loss in Trials

Newly published phase 3 trials show Eli Lilly's experimental triple-agonist drug retatrutide delivering the largest weight loss ever recorded in a medication trial.

On September 29, 2026, late-stage clinical trial data for Eli Lilly's experimental obesity drug retatrutide appeared in two major journals. A trial published in the New England Journal of Medicine found that patients with obesity on the highest 12 mg dose lost an average of 25 percent of their body weight after 80 weeks, and an average of 30 percent after an extension to 104 weeks. In a separate phase 3 TRIUMPH-2 study published in The Lancet, adults with type 2 diabetes and overweight or obesity lost an average of roughly 20 percent of their body weight over 80 weeks. The drug is not yet approved by the FDA, but Lilly plans to file for approval early next year.

NBC News reports the results represent the most weight loss ever recorded in a medication trial, with patients without diabetes losing up to 70 pounds and patients with severe obesity losing up to 85 pounds, or 30 percent of body weight, after 104 weeks — on par with bariatric surgery. In the diabetes population, the roughly 23 percent weight loss (up to 60 pounds) is especially striking, because people with type 2 diabetes have historically lost less weight on obesity medications. For comparison, NBC News notes that in earlier trials, people with type 2 diabetes lost up to 10 percent on semaglutide and up to 15 percent on tirzepatide, though those were not head-to-head comparisons. Vanderbilt obesity medicine specialist Dr. Gitanjali Srivastava told Everyday Health the results are 'impressive' precisely because of the population studied.

The obesity trial enrolled 2,339 participants at 131 sites in 11 countries, divided into four nearly equal groups receiving 4 mg, 9 mg, or 12 mg of retatrutide or a placebo. The average starting weight was around 113 kg with an average BMI of 40, and more than a third of participants on the drug lost 30 percent or more of their weight. In the diabetes trial, close to 1,200 participants were randomized across the same dose levels or placebo; at 12 mg, average weight loss reached 18.8 percent versus 5.1 percent for placebo, and A1C dropped by up to about 1.45 percent, with 72 percent of retatrutide participants reaching an A1C of 6.5 percent or lower. NBC News reports more than half of diabetes participants' BMI fell below the obesity cutoff of 30.

Retatrutide's benefits extended well beyond the scale. In the NEJM trial subset analyses, knee pain fell by up to 62 percent among participants with obesity-linked knee osteoarthritis, and sleep apnea events per hour dropped by up to 57 percent among those with obesity-linked obstructive sleep apnea. Cardiometabolic measures — blood pressure, triglycerides, and LDL cholesterol — improved across the board, and more than 90 percent of participants who began the trial with prediabetes had the condition resolve by its end. In the diabetes study, Everyday Health reports 72 percent of retatrutide participants reached an A1C of 6.5 percent or lower, and Duke endocrinologist Dr. Susan Spratt told NBC News the drug 'rivals gastric bypass surgery without the surgery.'

Retatrutide is a 'triple agonist,' a single synthetic peptide acting on GLP-1, GIP, and glucagon receptors — building on semaglutide's single target and tirzepatide's two. Side effects so far resemble existing GLP-1 drugs: mild-to-moderate nausea, diarrhea, and constipation, with some dizziness and low blood pressure reported. Per Ars Technica, the trial was too small to assess rarer risks such as pancreatitis and cardiovascular events, and it did not compare retatrutide head-to-head against tirzepatide. Meanwhile, experts warn against a thriving gray market: NBC News reports unauthorized copycat versions are sold through med spas and wellness platforms, prompting Lilly lawsuits, and Everyday Health quotes pharmacists and physicians urging people not to buy unregulated vials online.

Eli Lilly has not yet submitted retatrutide for FDA approval, but according to NBC News it plans to file early next year, putting one of the industry's most anticipated treatments on track for a regulatory decision. Key questions remain unanswered: whether retatrutide outperforms tirzepatide in direct comparison, how rare safety risks behave in larger and longer trials, and which patients the potent drug suits best. Duke's Dr. Michelle Ponder cautioned to NBC News that retatrutide 'may be too strong for some patients,' particularly those with mild diabetes or modestly elevated weight, who may do fine on existing medications. Experts told Everyday Health it may prove most valuable for people with obesity who need substantial weight loss to address serious complications like diabetes, sleep apnea, or joint disease.