Phase 2 RCT | Orforglipron, an oral GLP-1 receptor agonist, significantly reduces weight in adults with obesity

Summary: The article reports a phase 2, randomized, double-blind trial investigating the efficacy of the GLP-1 receptor agonist, orforglipron, as an oral weight loss treatment for adults with obesity or overweight plus at least one weight-related condition. The study involved 272 participants, who were administered orforglipron at varying doses or a placebo over a 36-week period.

The key findings of the study indicated significant weight reduction in individuals who were administered orforglipron. At 26 weeks, weight changes in the orforglipron group ranged from -8.6% to -12.6% compared to -2.0% in the placebo group. At 36 weeks, these figures were -9.4% to -14.7% for the orforglipron group and -2.3% for the placebo group. Furthermore, 46-75% of orforglipron recipients experienced a weight reduction of at least 10% by week 36, compared to 9% in the placebo group.

Improvements were also observed in all prespecified weight-related and cardiometabolic measures among orforglipron users. However, the treatment was associated with some mild to moderate gastrointestinal side effects, leading to discontinuation in 10-17% of participants. The safety profile was in line with other GLP-1 receptor agonists. These findings suggest that orforglipron could potentially be an effective oral treatment for weight reduction in adults with obesity, though further research is needed to corroborate these results and assess long-term effects.

Article: Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity – New England Journal of Medicine (link to abstract – $ for full-text)