Esophagus to Small Intestine
Lancet. 2023;402(10403):705–19
Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): A randomized, double-blind, placebo-controlled, phase 3 trial
Background: The authors assessed the efficacy and safety of the oral glucagon-like peptide-1 analogue, semaglutide 50 mg, taken once per day versus placebo for the treatment of overweight or obesity in adults without type 2 diabetes.
Methods: This randomized, double-blind, placebo-controlled, phase 3, superiority trial enrolled adults with a body mass index (BMI) of at least 30 kg/m2, or at least 27 kg/m2 with body weight-related complications and comorbidities, without type 2 diabetes. The trial was done at 50 outpatient clinics in 9 countries across Asia, Europe, and North America. Participants were randomly allocated (1:1) via an interactive web-response system to oral semaglutide escalated to 50 mg, or visually matching placebo, once per day for 68 weeks, plus lifestyle intervention. Group assignment was masked for participants, investigators, and those assessing outcomes. Coprimary end points were the percentage change in body weight and whether participants reached a body weight reduction of at least 5% at week 68 for oral semaglutide 50 mg versus placebo, assessed regardless of treatment discontinuation or use of other body weight-lowering therapies (an intention-to-treat analysis). Safety was assessed in participants who received at least 1 dose of trial drug.
Findings: From September 13 to November 22, 2021, 709 participants were screened, of whom 667 were randomly assigned to oral semaglutide 50 mg (n = 334) or placebo (n = 333). The estimated mean body weight change from baseline to week 68 was -15.1% (SE 0.5) with oral semaglutide 50 mg versus -2.4% (SE 0.5) with placebo (estimated treatment difference -12.7 percentage points, 95% confidence interval [CI]: -14.2 to -11.3; p < 0.0001). More participants reached body weight reductions of at least 5% (269 of 317 [85%] vs. 76 of 295 [26%]; odds ratio [OR] = 12.6, 95% CI: 8.5–18.7; p < 0.0001), 10% (220 [69%] vs. 35 [12%]; OR = 14.7, 95% CI: 9.6–22.6), 15% (170 [54%] vs. 17 [6%]; OR = 17.9, 95% CI: 10.4–30.7), and 20% (107 [34%] vs. 8 [3%]; OR = 18.5, 95% CI: 8.8–38.9) at week 68 with oral semaglutide 50 mg versus placebo. Adverse events were more frequent with oral semaglutide 50 mg (307 of 334 [92%]) than with placebo (285 of 333 [86%]). Gastrointestinal adverse events (mostly mild to moderate) were reported in 268 participants (80%) with oral semaglutide 50 mg and 154 (46%) with placebo.
Interpretation: In adults with overweight or obesity without type 2 diabetes, oral semaglutide 50 mg once per day led to a superior and clinically meaningful decrease in body weight compared with placebo.