Eli Lilly has unveiled groundbreaking Phase 3 clinical trial results for its next-generation obesity drug, retatrutide. Patients in the highest-dose group achieved an average weight loss of 28.7% after 68 weeks of treatment—significantly surpassing existing therapies, including Lilly’s own Zepbound (~22.5%) and Novo Nordisk’s Wegovy (under 20%). The news drove Lilly’s shares up 1.6% overnight.
The trial, targeting obese patients with knee osteoarthritis, demonstrated that the highest retatrutide dose reduced body weight by 28.7% (approximately 71.2 lbs) over 68 weeks. This efficacy far exceeds Lilly’s marketed drug Zepbound and rival Wegovy.
The positive data immediately resonated in financial markets, with Lilly’s stock rising 1.2% in premarket trading and closing 1.6% higher. Analysts suggest retatrutide could establish a new blockbuster franchise for Lilly, building on the explosive growth of drugs like Mounjaro and Zepbound.
Retatrutide’s mechanism involves mimicking three gut hormones to regulate appetite and potentially boost energy expenditure, making it more complex than current options. Beyond weight loss, the drug also showed promise in alleviating knee pain, expanding its potential applications.
Kenneth Custer, Lilly’s president of cardiovascular and metabolic health, stated, “We believe retatrutide could become a critical option for patients with significant weight loss needs and specific comorbidities, including knee osteoarthritis.” The company expects seven additional Phase 3 trials for the drug to conclude by 2026.
**Record Efficacy, but Higher Side Effects** The trial enrolled non-diabetic patients with a BMI ≥35 and knee osteoarthritis. Over 68 weeks, participants received weekly retatrutide or placebo injections. The highest-dose group achieved the unprecedented 28.7% weight loss.
However, the drug’s potency came with gastrointestinal side effects like nausea and diarrhea, consistent with existing obesity treatments. JPMorgan analyst Chris Schott noted retatrutide’s side-effect profile was more pronounced than Wegovy or Zepbound but remained typical for the class. Notably, some participants discontinued treatment due to excessive weight loss, suggesting the drug may target extremely high-BMI patients.
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