Eli Lilly has reported impressive results from a large Phase 3 clinical trial of its experimental obesity drug, retatrutide. The drug helped patients lose significantly more weight than expected and also reduced knee pain linked to osteoarthritis. However, some patients stopped treatment due to side effects, raising questions about how well people can tolerate the medication long term.
Retatrutide is a once-weekly injectable drug that works on three hormone receptors: GLP-1, GIP, and glucagon. This “triple agonist” approach is designed to go beyond Lilly’s existing obesity drugs, such as Zepbound and Mounjaro, which target only two hormones.
The Phase 3 trial, called Triumph-4, included 445 adults who were obese or overweight and had knee osteoarthritis. After 68 weeks, patients who stayed on the highest dose (12 mg) lost an average of 28.7% of their body weight—about 71 pounds. Those on a lower 9 mg dose lost 26.4%, or roughly 64 pounds. When all patients were included, even those who dropped out, weight loss on the highest dose averaged 23.7%.
The study also looked at joint pain. Patients taking retatrutide reported about a 75% reduction in knee pain, compared with a 40% reduction in the placebo group. Both weight loss and pain reduction goals were successfully met.
Despite these strong results, tolerability was an issue. About 18% of patients on the highest dose stopped treatment because of side effects, compared with just 4% on placebo. Some patients experienced nausea or unusual skin sensations, though most cases were mild. Dropout rates were lower in patients with more severe obesity.
Eli Lilly plans to continue studying retatrutide in several additional trials for obesity and type 2 diabetes. While the drug shows major promise, balancing effectiveness with patient comfort will be key to its future success.
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