Eli Lilly said Thursday that its experimental anti-obesity medication retatrutide helped people in a large phase three trial lose far more weight than drugs already on the market. In the study, 2,339 adults with obesity or overweight and at least one weight-related comorbidity, but no diabetes, were randomized to receive retatrutide or placebo.
At the highest 12mg dose, participants lost an average of 70.3lbs, or 28.3%, over 80 weeks. That compares with 64.4lbs, or 25.9%, on the 9mg dose and 47.2lbs, or 19.0%, on the 4mg dose, even with only a single dose-escalation step. Susan Spratt called the result exceptional, saying, “This is the largest weight loss I’ve ever seen in any medication trial.”
The size of the loss matters because Lilly is trying to position retatrutide against a fast-moving obesity-drug market led by its own Zepbound and Novo Nordisk’s Wegovy. Lilly said users of Zepbound can expect to lose about 15% to 20% of starting body weight over 72 weeks, while Wegovy users can expect to lose about 14% to 19% over 64 to 72 weeks. Retatrutide is a once-weekly triple hormone receptor agonist that acts on GLP-1 and GIP and also includes glucagon activity.
The higher-dose results also moved a meaningful share of patients toward a body mass index below the obesity range. Lilly said 45.3% of participants on 12mg lost at least 30% of their weight, 65.3% reduced their BMI below 30, and 37.5% of those who began the trial with a BMI of 40 or higher also dropped below 30. For many patients, that kind of shift would not mean a cure, but it could mark a major change in health risk.
The tradeoff was side effects, which were common and rose with dose. Nausea affected 28.6% of participants on 4mg, 38.4% on 9mg and 42.4% on 12mg, compared with 14.8% on placebo. Diarrhea was reported in 25.2%, 34.1% and 32.0% of the three dose groups, versus 13.5% on placebo. Constipation affected roughly one-quarter of treated patients, compared with 10.9% of placebo users, while vomiting occurred in up to one in four people on the highest dose, versus 4.8% on placebo. Upper respiratory tract infections were also reported in the trial, with rates of 14.2% on 4mg, 12.2% on 9mg and 13.1% on 12mg, compared with 11.6% in the placebo group.
The results do not put retatrutide on pharmacy shelves yet, but they do show why drugmakers are racing to build the next generation of obesity treatments. If the findings hold up in later review, Lilly would have a candidate that appears capable of producing weight loss beyond what is now available, though it comes with the same familiar question facing every drug in this class: how much benefit patients will accept alongside side effects that can be hard to ignore.
