Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity.

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Study Summary

2339 adults with obesity without diabetes were randomized to receive once-weekly subcutaneous retatrutide (4 mg, 9 mg, or 12 mg) or placebo. The primary outcomes of interest were percentage change in body weight, change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores among patients with knee osteoarthritis, and change in the apnea–hypopnea index (AHI) among patients with obstructive sleep apnea. Secondary outcomes included weight reduction thresholds, waist circumference, cardiometabolic measures, physical functioning, quality of life, and adverse events. Outcomes were assessed at 80 weeks, with an extension phase evaluating weight loss at 104 weeks. Overall, the results revealed that retatrutide produced significantly greater weight loss than placebo, with reductions reaching 25.0% at the 12-mg dose compared with 3.9% with placebo. Retatrutide also significantly reduced knee osteoarthritis pain and obstructive sleep apnea severity. These findings suggested that retatrutide was effective for substantial weight reduction while improving important obesity-related complications.