The New England Journal of MedicineTriple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial

The trial was a phase 2, double-blind, randomized, placebo-controlled study including adults with a BMI of 30 or higher, or 27 to less than 30 with at least one weight-related condition.

The latest findings from a phase 2 trial offer promising results for the use of retatrutide, a tri-agonist, in the management of obesity. This study has shed light on its dose-response relationships, efficacy, safety, and associated side effects.

Key Points:

• Participants received various doses of retatrutide or placebo once weekly for 48 weeks.
• The primary end point was the percentage change in body weight from baseline to 24 weeks, secondary end points included changes at 48 weeks and reductions of 5% or more, 10% or more, or 15% or more.
• At 48 weeks, the least-squares mean percentage change in body weight in the retatrutide groups was between -8.7% (1-mg group) and -24.2% (12-mg group), compared to -2.1% in the placebo group.

Additional Points:

• At 48 weeks, weight reductions of 5% or more, 10% or more, and 15% or more occurred in 92%, 75%, and 60%, respectively, of participants receiving 4 mg of retatrutide, and up to 100%, 93%, and 83% of those receiving 12 mg.
• The most common adverse events were gastrointestinal and were partially mitigated with a lower starting dose. Dose-dependent increases in heart rate peaked at 24 weeks and declined thereafter.

Conclusion:

• Retatrutide treatment for 48 weeks resulted in substantial reductions in body weight among adults with obesity, suggesting its potential as a new therapeutic option.

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Did You Know?
As per the World Health Organization, in 2016, more than 1.9 billion adults were overweight, and of these, over 650 million were obese.