ADA: Once-Daily Orforglipron Linked to Significant Weight Reduction

Weight reduction of at least 10 percent occurred in 46 to 75 percent receiving orforglipron by week 36
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Medically Reviewed By:
Mark Arredondo, M.D.

MONDAY, June 26, 2023 (HealthDay News) -- The nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist orforglipron as a once-daily oral therapy is associated with clinically significant weight reduction, according to a study published online June 23 in the New England Journal of Medicine to coincide with the annual meeting of the American Diabetes Association, held from June 23 to 26 in San Diego.

Sean Wharton, M.D., from McMaster University in Toronto, and colleagues conducted a randomized trial enrolling adults with obesity or with overweight plus at least one weight-related coexisting condition, without diabetes. A total of 272 participants were randomly assigned to 36 weeks of orforglipron at 12, 24, 36, or 45 mg or placebo once daily.

The researchers found that the mean body weight was 108.7 kg at baseline and mean body mass index was 37.9 kg/m2. The mean change from baseline in body weight ranked from −8.6 to −12.6 percent across the orforglipron dose cohorts at week 26, and was −2.0 percent with placebo. The mean change ranged from −9.4 to −14.7 percent with orforglipron and was −2.3 percent with placebo at 36 weeks. By week 36, a weight reduction of at least 10 percent occurred in 46 to 75 percent receiving orforglipron and 9 percent receiving placebo; a weight reduction of at least 15 percent occurred in 48 and 1 percent of those receiving orforglipron 45 mg and placebo, respectively. The safety profile was consistent with that of the GLP-1 receptor agonist class.

"Further studies are needed to establish whether the health benefits seen with injectable GLP-1 receptor agonists are shared by orforglipron," the authors write.

Several authors disclosed ties to pharmaceutical companies, including Eli Lilly, which manufactures orforglipron and funded the study.

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