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Eli Lilly’s New “Triple G” Drug Shows Unprecedented Weight Loss and Arthritis Relief in Clinical Trial
Eli Lilly is making waves in the obesity treatment landscape with its latest drug, retatrutide, which has demonstrated what appears to be the highest weight loss observed in a late-stage trial to date. Beyond its significant impact on weight, the weekly injection also showed promising results in reducing knee arthritis pain, marking a successful first step in a series of upcoming studies.
Dubbed the “triple G” drug, retatrutide takes a unique approach by mimicking three hunger-regulating hormones-GLP-1, GIP, and glucagon-a more comprehensive strategy compared to existing treatments that target only one or two. This multi-pronged action appears to have a more potent effect on appetite and food satisfaction.
In the TRIUMPH-4 study, the highest dose of retatrutide helped patients with obesity and a specific type of knee arthritis achieve an average body weight reduction of 23.7% over 68 weeks, considering all participants, including those who discontinued treatment. For patients who completed the entire course, the average weight loss climbed to an impressive 28.7%. Remarkably, some patients experienced such significant weight loss that they opted to withdraw from the trial.
“It’s incredible,” stated Dr. Caroline Apovian, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital.
“Now, we have a drug that rivals the weight loss benefits of surgery.” Dr.
Apovian suggests Eli Lilly is strategically positioning this drug for individuals with severe obesity, noting that 84% of trial participants had a body mass index (BMI) above 35 or 40.
Beyond weight loss, retatrutide also met its secondary goal of reducing pain from knee osteoarthritis, a common condition causing joint pain and stiffness. The drug led to an average pain reduction of up to 62.6%, with over 1 in 8 patients experiencing complete freedom from knee pain by the trial’s end.
This is particularly significant given concerns about lean muscle mass loss with current weight loss drugs; Dr. Apovian highlighted that the results indicate improved physical function in adults with severe obesity.
These findings have exceeded Wall Street’s expectations, with Eli Lilly’s shares rising over 3% on Thursday. BMO Capital Markets analyst Evan Seigerman had projected a weight loss of 20% to 23% and at least a 50% reduction in knee pain, both of which retatrutide surpassed. Kenneth Custer, president of Lilly Cardiometabolic Health, expressed confidence that retatrutide “could become an important option for patients with significant weight loss needs and certain complications, including knee osteoarthritis.”
While the efficacy data is compelling, some observations regarding tolerability were noted. JPMorgan analyst Chris Schott commented that retatrutide’s tolerability data was “somewhat worse vs Zepbound, though not surprising.”
Approximately 18% of patients on the highest dose discontinued treatment due to side effects, compared to 4% in the placebo group. Eli Lilly attributed these discontinuations to a strong correlation with patients’ starting BMI and instances of “perceived excessive weight loss.”
Common side effects included nausea (43% on the highest dose), diarrhea (33%), and vomiting (20.9%). Over 1 in 5 patients also experienced dysesthesia, an unpleasant nerve sensation, which was generally mild and rarely led to treatment discontinuation.
It’s important to note that the TRIUMPH-4 study was not solely focused on weight loss, meaning future trials specifically designed for that outcome could potentially yield different or even higher results. Eli Lilly anticipates releasing findings from seven additional Phase 3 trials for retatrutide by the end of 2026.
Retatrutide’s unique “triple G” mechanism sets it apart from competitors. For comparison, tirzepatide (the active ingredient in Eli Lilly’s Zepbound) mimics GLP-1 and GIP, while semaglutide (the active ingredient in Novo Nordisk’s Wegovy) targets only GLP-1. Higher doses of tirzepatide previously showed an average weight loss of roughly 20.9% in late-stage studies.
As Eli Lilly establishes a strong position in this field, rival Novo Nordisk is actively working to catch up. In March, Novo Nordisk acquired rights to an early experimental drug from United Laboratories International, a potential competitor to retatrutide due to its similar three-pronged approach to weight loss and blood sugar regulation. However, Novo Nordisk’s acquired treatment is still in much earlier stages of development and will require several years before it becomes available to patients.