(NEJM Journal Watch)-For both diabetes and obesity, semaglutide was more effective at higher doses.

The oral formulation of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide is approved by the U.S. FDA at doses as high as 14 mg daily for treating patients with type 2 diabetes. But unlike the subcutaneous form, the oral form is not approved for treating obesity in patients without diabetes. In two recent manufacturer-sponsored trials, researchers examined higher doses of oral semaglutide for diabetes and obesity.

In one study, researchers randomized 1600 patients with glycosylated hemoglobin (HbAic) of 8.0% to 10.5% and body-mass index (BMI) ≥25 kg/m2 (mean BMI, 34 kg/m?) to receive oral semaglutide – 14 mg, 25 mg, or 50 mg daily – in addition to their previous oral antidiabetic medications; patients who used insulin were excluded. After 52 weeks, mean changes in HbA1c c 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. At baseline, mean BMI was 38 kg/m2. 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.