New Oral GLP-1 Agonist for Obesity, Type 2 Diabetes

26 Jun 2023 • Orforglipron, an investigational oral daily nonpeptide glucagon-like peptide-1 (GLP-1) agonist that can be taken with or without food, appears comparable with other injectable and oral agents in the class for treating obesity and type 2 diabetes, suggest two new phase 2 studies. The results of the phase 2 trial of orforglipron in the treatment of adults with overweight or obesity were presented June 23 at the American Diabetes Association (ADA) 83rd Scientific Sessions, and the findings simultaneously published in the New England Journal of Medicine.

  • The phase 2 double-blind trial included 272 adults with obesity or with overweight plus at least one weight-related complication, with or without diabetes.
  • They were randomized to receive orforglipron in doses of 12 mg, 24 mg, 36 mg, or 45 mg, or placebo once daily for 36 weeks.
  • The proportion of patients achieving weight loss of at least 10% by week 36 was 46% to 75% with orforglipron, compared to 9% with placebo.
  • As with other GLP-1 agonists, the most commonly reported adverse events were gastrointestinal, mostly mild to moderate, occurring primarily during dose escalation.

The study, "establishes this novel and highly effective small molecule GLP-1 receptor agonist [orforglipron] as a potentially competitive alternative to injectable GLP-1 receptor agonists and oral semaglutide, with the added advantage of requiring less burdensome precautions to achieve satisfactory bioavailability after oral administration," researchers conclude.

Source: NEJM | Read full story

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