Oral Orforglipron Yields Greater Weight Reductions Than Placebo
THURSDAY, Sept. 25, 2025 -- For adults with obesity who do not have diabetes, the oral glucagon-like peptide-1 receptor agonist orforglipron yields significantly greater reductions in body weight than placebo, according to a study published online Sept. 16 in the New England Journal of Medicine to coincide with the annual meeting of the European Association for the Study of Diabetes, held Sept. 15 to 19 in Vienna.
Sean Wharton, M.D., from McMaster University in Hamilton, Ontario, Canada, and colleagues conducted a phase 3 randomized trial to examine the safety and efficacy of once-daily orforglipron at doses of 6, 12, or 36 mg as compared to placebo as an adjunct to healthy diet and physical activity in a trial involving 3,127 adults with obesity without diabetes.
The researchers found that from baseline to week 72, the mean change in body weight was −7.5, −8.4, and −11.2 percent with 6, 12, and 36 mg orforglipron, respectively, compared with −2.1 percent with placebo. Among patients in the orforglipron 36-mg group, 54.6, 36.0, and 18.4 percent had a reduction of ≥10, ≥15, and ≥20 percent as compared with 12.9, 5.9, and 2.8 percent of patients, respectively, in the placebo group. Significant improvement was seen in waist circumference, systolic blood pressure, triglyceride levels, and non-high density lipoprotein cholesterol levels with orforglipron treatment versus placebo. In 5.3 to 10.3 percent of patients in the orforglipron groups and in 2.7 percent of patients in the placebo group, adverse events resulted in treatment discontinuation.
"This could mean an expansion of obesity interventions to groups who are currently excluded due to the cost of and lack of access to injectable medications," Wharton said in a statement.
Several authors disclosed ties to pharmaceutical companies, including Eli Lilly, which is developing orforglipron and funded the study.
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