Eli Lilly said Thursday that its experimental obesity drug retatrutide helped participants in a large trial lose far more weight than people taking other weight-loss medicines already on the market. In the highest-dose group, adults in the study lost an average of 70.3 pounds, or 28.3%, over 80 weeks.
The result puts retatrutide at the center of the next race in obesity treatment, and it does so with a number that is hard to ignore. In the same study, 45.3% of participants receiving the 12mg dose lost at least 30% of their body weight, a level that drew strong reaction from Boston University endocrinologist Susan Spratt, who said the finding was the largest weight loss she had ever seen in any medication trial and called it huge.
Eli Lilly’s phase three trial enrolled 2,339 adults who had obesity or were overweight, had at least one weight-related comorbidity, and did not have diabetes. They were randomized to receive retatrutide in 4mg, 9mg or 12mg doses, or a placebo, and followed for 80 weeks. The 9mg group lost an average of 64.4 pounds, or 25.9%, while the 4mg group lost 47.2 pounds, or 19.0%, despite only a single dose-escalation step.
The weight-loss profile now reported appears to go beyond what has typically been seen with the company’s approved Zepbound and with Novo Nordisk’s Wegovy. Zepbound users can expect to lose an average of 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. In the retatrutide trial, 65.3% of people on the 12mg regimen reduced their BMI below 30, and 37.5% of those who began with a BMI of 40 or higher fell below that threshold.
Retatrutide is a once-weekly triple hormone receptor agonist that acts on GLP-1, GIP and glucagon. That combination is one reason researchers are watching it closely, but the trial also showed the familiar drag of side effects. Nausea was reported in 28.6% of participants receiving 4mg, 38.4% on 9mg and 42.4% on 12mg, compared with 14.8% in the placebo group. Diarrhea affected 25.2% on 4mg, 34.1% on 9mg and 32.0% on 12mg, versus 13.5% on placebo.
Constipation was reported by roughly one-quarter of treated patients, compared with 10.9% of those receiving placebo. Vomiting occurred in up to one in four patients on the highest dose, versus 4.8% in the placebo group. Upper respiratory tract infections were reported in 14.2% of patients on 4mg, 12.2% on 9mg and 13.1% on 12mg, compared with 11.6% on placebo.
The significance of Thursday’s announcement is straightforward: Lilly has now shown that retatrutide may deliver weight-loss results that exceed the levels most patients and doctors have come to expect from today’s leading drugs, but it has not done so without tolerability problems. For now, the headline number is the one that will drive the conversation, and the side effects are the reason the next phase of scrutiny will be just as important as the first.
