13 Jul 2023 • For both diabetes and obesity, semaglutide was more effective at higher doses. The oral formulation of the glucagon-like peptide-1 (GLP-1) inhibitor semaglutide is approved by the U.S. FDA at doses as high as 14 mg daily for treating patients with type 2 diabetes. In two recent trials, researchers examined higher doses of oral semaglutide for diabetes and obesity.

• In one study, researchers randomized 1600 patients with HbA1c of 8.0% to 10.5% and BMI ≥25 kg/m2 to receive oral semaglutide — 14 mg, 25 mg, or 50 mg daily — in addition to their previous oral antidiabetic medications.

• After 52 weeks, mean changes in HbA1c in the three groups were −1.5%, −1.8%, and −2.0%, respectively.

• Mean percentage changes in body weight were −4.7%, −7.3%, and −8.5%, respectively.

• The other study involved only patients without diabetes.

• Researchers randomized 600 patients with BMI ≥30 kg/m2, or BMI ≥27 kg/m2 plus weight-related complications other than diabetes, to receive oral semaglutide (escalated to 50 mg daily) or placebo, in addition to lifestyle intervention.

• After 68 weeks, mean changes in body weight were −15% and −2% with semaglutide and placebo, respectively; 54% of patients who took semaglutide, compared with 6% of those who took placebo, lost ≥15% of their baseline body weight.

In both studies, the most frequent adverse effects were mild-to-moderate nausea, vomiting, and diarrhea, primarily during dose escalation. Doses of oral semaglutide higher than those currently approved appear to be tolerated reasonably well and to be increasingly effective for short-term management of both diabetes and obesity as dosages increase. Notably, weight loss was substantially greater in patients without diabetes than in those with diabetes.

Source: NEJM | Read full story