Study summary · research use only
Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This phase 3, randomized, double-blind trial in 3127 adults with obesity but without diabetes tested once-daily oral orforglipron (6 mg, 12 mg, or 36 mg) versus placebo over 72 weeks. Body weight change from baseline to week 72 was -7.5%, -8.4%, and -11.2% across doses, versus -2.1% with placebo (P<0.001). In the 36-mg group, 54.6% lost 10% or more of body weight, 36.0% lost 15% or more, and 18.4% lost 20% or more, versus 12.9%, 5.9%, and 2.8% with placebo. Waist circumference, blood pressure, triglycerides, and non-HDL cholesterol also improved more with orforglipron. Treatment discontinuation from adverse events occurred in 5.3 to 10.3% of orforglipron groups versus 2.7% with placebo; the most common adverse events were mostly mild to moderate gastrointestinal effects.
Abstract
Orforglipron, a small-molecule, nonpeptide oral glucagon-like peptide-1 (GLP-1) receptor agonist, is being investigated as a treatment for obesity. In this phase 3, multinational, randomized, double-blind trial, we examined the safety and efficacy of once-daily orforglipron at doses of 6 mg, 12 mg, or 36 mg, as compared with placebo (assigned in a 3:3:3:4 ratio) as an adjunct to healthy diet and physical activity for 72 weeks. All the patients had obesity without diabetes mellitus. The primary end point was the percent change in body weight from baseline to week 72, as assessed according to the treatment-regimen estimand in the intention-to-treat population. A total of 3127 patients underwent randomization. The mean change in body weight from baseline to week 72 was -7.5% (95% confidence interval [CI], -8.2 to -6.8) with 6 mg of orforglipron, -8.4% (95% CI, -9.1 to -7.7) with 12 mg of orforglipron, and -11.2% (95% CI, -12.0 to -10.4) with 36 mg of orforglipron, as compared with -2.1% (95% CI, -2.8 to -1.4) with placebo (P<0.001 for all comparisons with placebo). Among the patients in the orforglipron 36-mg group, 54.6% had a reduction of 10% or more, 36.0% had a reduction of 15% or more, and 18.4% had a reduction of 20% or more, as compared with 12.9%, 5.9%, and 2.8% of the patients, respectively, in the placebo group. Waist circumference, systolic blood pressure, triglyceride levels, and non-HDL cholesterol levels significantly improved with orforglipron treatment as compared with placebo. Adverse events resulted in treatment discontinuation in 5.3 to 10.3% of the patients in the orforglipron groups and in 2.7% of those in the placebo group. The most common adverse events with orforglipron were gastrointestinal effects, which were mostly mild to moderate. In adults with obesity, 72-week treatment with orforglipron led to significantly greater reductions in body weight than placebo; the adverse-event profile was consistent with that of other GLP-1 receptor agonists. (Funded by Eli Lilly; ATTAIN-1 ClinicalTrials.gov number, NCT05869903.).
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