Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity
N Engl J Med. 2023; DOI: 10.1056/NEJMoa2302392
Orforglipron is a once-daily oral nonpeptide GLP-1RA in development for weight management and the treatment of T2D. This phase 2 double-blind trial evaluated the efficacy and safety of orforglipron in adults with obesity, or with overweight plus at least one weight-related coexisting condition, and without T2D. In total, 272 participants were randomised to orforglipron (12, 24, 36 or 45 mg) or placebo once daily for 36 weeks, with a primary endpoint of change from baseline in body weight at week 26.
At week 26, the mean change from baseline in body weight ranged from −8.6% to −12.6% across the orforglipron dose cohorts and was −2.0% in the placebo group. At week 36, the mean change ranged from −9.4% to −14.7% with orforglipron and was −2.3% with placebo. A weight reduction of at least 10% by week 36 occurred in 46% to 75% of the participants who received orforglipron compared with 9% who received placebo. The most common AEs reported with orforglipron were similar to those with injectable GLP-1RAs, namely gastrointestinal events, which were mild to moderate, occurred primarily during dose escalation, and led to discontinuation of orforglipron in 10% to 17% of participants.
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