Eli Lilly's Next-Generation Obesity Drug Achieves 28.3% Average Weight Loss in Pivotal Trial

Eli Lilly said on Thursday that its next-generation obesity drug retatrutide achieved its main goals in a key late-stage trial, with the highest 12-milligram dose group experiencing an average weight loss of 28.3% over 80 weeks, compared to 2.2% in the placebo group. Among the approximately 2,500 participants, more than 45% of patients achieved weight loss of 30% or more.

This outcome significantly brings retatrutide closer to the regulatory submission stage. For Eli Lilly, it is not only another weight loss product following Zepbound but also a core asset for the company to maintain its market advantage in the long term within the fields of obesity and diabetes. Retatrutide simultaneously targets the GLP-1, GIP, and glucagon receptors, advancing beyond the mechanism of existing mainstream GLP-1/GIP dual-target drugs and is considered the next important pillar in the obesity drug pipeline following Zepbound.

About 65% of patients in the highest dose group had a BMI reduced to below 30 at 80 weeks, escaping the obesity diagnosis category; among patients with a BMI of ≥35 participating in the extended phase study, the average weight loss reached 30.3% over 104 weeks. Dan Skovronsky, Chief Scientific and Product Officer at Eli Lilly, said in an interview with CNBC that a 30% weight loss is "unbelievable," a level usually only achievable through weight loss surgery in the past.

However, greater efficacy also comes with a higher incidence of side effects. In the highest dose group, the incidence of nausea was 42%, diarrhea 32%, constipation 26.1%, and the proportion of patients discontinuing the drug due to side effects was 11.3%. This means that the therapeutic advantage must be weighed against tolerance, with some analysts previously worrying that the side effect incidence of retatrutide could be higher than Eli Lilly's Mounjaro, potentially offsetting its therapeutic advantage to some extent. Eli Lilly responded by saying that the safety profile of retatrutide is generally consistent with other GLP-1 containing drugs, with no observed safety issues related to the heart or liver.

The low-dose option provides another differentiated commercial pathway for Eli Lilly. The 4-milligram dose group achieved an average weight loss of 19% over 80 weeks, with the proportion discontinuing due to side effects at about 4%, lower than the nearly 5% of the placebo group. Skovronsky said that the weight loss effect of this low dose is close to that of the high dose Zepbound, while the tolerance performance exceeded the company's expectations. In the future, the company is expected to cover patient groups with different risk preferences through different dosages.

On the competitive front, the results of this trial further solidify Eli Lilly's first-mover advantage in the obesity drug market. The company currently holds a 60.1% share in the US market for obesity and diabetes drugs, with Novo Nordisk at 39.4%. Although Novo Nordisk has strengthened its three-target weight loss drug pipeline through deals, the relevant products are still in an earlier stage of development.