Orforglipron Achieves Up to 12% Weight Loss in Obesity Phase 3 Study: Daily Dose

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On September 17, 2025, we reported on results from the phase 3 ATTAIN-1 clinical trial presented at the European Association for the Study of Diabetes (EASD) 2025, September 15-19, in Vienna, Austria.

The study

Investigators conducted a randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of investigational once-daily oral orforglipron 6 mg, 12 mg and 36 mg as a monotherapy to placebo in 3127 adults with obesity, or overweight with at least 1 of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease, who did not have diabetes.

The primary endpoint 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.

The findings

At 72 weeks, participants receiving the highest dose of orforglipron lost an average of 27.3 lbs (12.4%) from baseline, compared with 2.2 lbs (0.9%) with placebo. All 3 doses of orforglipron (6 mg, 12 mg, and 36 mg) met the primary endpoint of superior body weight reduction vs placebo.

Among 1127 participants with prediabetes at baseline, up to 91% of those treated with orforglipron achieved near-normal blood glucose levels at 72 weeks versus 42% on placebo. The agent was also associated with reductions in waist circumference, non-HDL cholesterol, triglycerides, and systolic blood pressure. In an exploratory analysis, the highest dose reduced high-sensitivity C-reactive protein levels by 47.7%.

Authors' comments

"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."

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