Oral GLP-1 Orforglipron Shows Meaningful Weight Loss in Phase 3 Trial

Positive results have been announced from a phase 3 trial evaluating the efficacy and safety of orforglipron for weight loss in adult patients with overweight or obesity, Eli Lilly announced in a release.¹ The therapy is an investigational, small molecule, oral glucagon-like peptide-1 (GLP-1) receptor agonist that can be taken without restrictions on food or water at any time of day.

Data from the ATTAIN-1 (NCT05869903) clinical trial showed orforglipron met its primary end point of mean percent change in body weight from baseline. The therapy also met all key secondary end points, including mean change in waist circumference from baseline, mean change in systolic blood pressure from baseline, and mean percent change in fasting non–high-density lipoprotein (HDL) cholesterol from baseline.

"Obesity is one of the most pressing global health challenges of our time, driving global chronic disease burden and impacting more than one billion people worldwide," Kenneth Custer, PhD, MBA, executive vice president and president of Lilly Cardiometabolic Health, said in a release.¹ "With orforglipron, we're working to transform obesity care by introducing a potential once-daily oral therapy that could support early intervention and long-term disease management, while offering a convenient alternative to injectable treatments.”

ATTAIN-1 is a 72-week, randomized, double-blind, placebo-controlled phase 3 study evaluating the efficacy and safety orforglipron for weight loss in adult patients with overweight or obesity, with weight-related comorbidities and without diabetes. The primary study end point is superior body weight reduction compared with placebo.

The study includes 3127 adult patients who were randomly assigned to 1 of 4 cohorts: 6 mg orforglipron once daily, 12 mg orforglipron once daily, 36 mg orforglipron once daily, or placebo. All patients initially started on 1 mg orforglipron, which was increased in a step-wise approach every 4 weeks until their assigned dose was met. The trial took place at sites in the United States, Brazil, China, India, Japan, South Korea, Puerto Rico, Slovakia, Spain, and Taiwan.

The study data showed that patients who took the highest dose of orforglipron lost an average of 27.3 lb at 72 weeks compared with 2.2 lb for patients taking placebo. Of the patients taking the highest dose of orforglipron, 59.6% lost at least 10% of their body weight, and 39.6% lost at least 15%. The therapy was also associated with reductions in known markers of cardiovascular risk, including non-HDL cholesterol, triglycerides, and systolic blood pressure.

Additionally, the overall safety profile of orforglipron was consistent with the established GLP-1 receptor agonist class. The most common adverse events during the study were constipation, nausea, diarrhea, and vomiting.

Lilly said it plans to present more detailed data from the ATTAIN-1 trial at the European Association for the Study of Diabetes (EASD) Annual Meeting 2025. The company also said that it expects data later this year from the ACHIEVE phase 3 clinical trial program, which is evaluating orforglipron in adult patients with type 2 diabetes.

“With these positive data in hand, we are now planning to submit orforglipron for regulatory review by year-end and are prepared for a global launch to address this urgent public health need," Custer said in the release.¹

READ MORE: Obesity Management Resource Center

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Reference

1. Lilly's oral GLP-1, orforglipron, delivers weight loss of up to an average of 27.3 lb in first of two pivotal phase 3 trials in adults with obesity. News release. Eli Lilly and Company. August 7, 2025. Accessed August 7, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-oral-glp-1-orforglipron-delivers-weight-loss-average-273