Once-daily oral semaglutide 50 mg induces 15.1% weight loss in adults with overweight or obesity without type 2 diabetes (T2D) compared to placebo when used alongside diet and exercise, according to results from the phase 3 OASIS-1 randomized controlled trial.
Findings were presented at the 83rd Scientific Sessions of the American Diabetes Association® (ADA) in San Diego, CA, and were simultaneously published in The Lancet.
“To our knowledge, this was the first trial to assess the body weight-lowering effect of an oral GLP-1 analogue (semaglutide 50 mg taken once per day) in adults with overweight or obesity, without type 2 diabetes,” wrote authors. “The study showed that, in this population, oral semaglutide 50 mg induced clinically meaningful reductions in body weight, with accompanying improvements in cardiometabolic risk factors.”
In 2019, the US Food and Drug Administration approved oral semaglutide (Rybelsus, Novo Nordisk) as the first oral GLP-1 receptor agonist for adults with T2D. In clinical trials leading to that approval, accompanying body weight reductions were observed. The approval was for a dose of up to 14 mg.
Researchers conducted the OASIS 1 trial to evaluate the efficacy and safety of a much higher daily dose of the oral agent, 50 mg, plus lifestyle intervention compared with placebo for the treatment of overweight or obesity in adults without T2D.
Adults aged ≥18 years with a body mass index (BMI) of at least 30 kg/m2 or a BMI of at least 27 kg/m2 with at least 1 body weight-related comorbidity and 1 self-reported dietary weight-loss effort were randomly assigned, 1:1, to receive oral semaglutide 50 mg or placebo once per day for 68 weeks as an adjunct to lifestyle intervention.
The coprimary endpoints 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 compared with placebo, according to the study. Investigators assessed these endpoints regardless of treatment discontinuation or the use of other weight-lowering therapies (an intention-to-treat analysis).
Researchers also analyzed how many participants achieved a 10%, 15%, and 20% body weight reduction and changes in absolute body weight, BMI, waist circumference, cardiometabolic parameters, and fasting lipids. The Impact of Weight on Quality of Life–Lite Clinical Trials Version (IWQOL-Lite-CT) and the Short Form-36v2 Health Survey acute version were used to measure physical function.
A total of 667 adults (mean age, 67 years; 74% White; 73% women) from 50 outpatient clinics across Asia, Europe, and North America were enrolled in the study and assigned to oral semaglutide 50 mg (n=334) or placebo (n=333).
OASIS investigators found that in the treatment-policy estimand, adults who received oral semaglutide lost 15.1% of their body weight at 68 weeks compared with a 2.4% weight loss for placebo (estimated treatment difference -12.7 percentage points, 95% CI -14.2 to -11.3; P<.001).
Further, more participants reached body weight reductions of at least 5% (85% vs 26%), 10% (69% vs 12%), 15% (54% vs 6%), and 20% (34% vs 3%) at week 68 with oral semaglutide 50 mg compared to placebo.
“These findings were accompanied by substantial improvements in physical functioning scores and cardiometabolic risk factors compared with placebo,” wrote study authors.
Adverse events were reported by 92% of the oral semaglutide group and 86% of the placebo group. Serious adverse events occurred in 10% of those receiving semaglutide and 9% receiving placebo. Gastrointestinal adverse events, mostly mild-to-moderate, were observed in 80% of adults who received oral semaglutide and in 46% of those who received placebo, according to the study.
“Having an oral formulation of semaglutide in addition to the subcutaneous, or injectable, formula available will allow people who struggle to lose weight with diet and physical activity alone to take this effective medication in a way that best suits them,” said first author Filip Knop MD, PhD, professor of endocrinology and director of the Center for Clinical Metabolic Research at Gentofte Hospital, University of Copenhagen in Denmark, in an ADA press release. “The weight loss also led to improvements in physical functioning, allowing participants to have an improved quality of life for everyday activities.”
Reference: Knop FK, Aroda VR, Garvey WT, et al. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. Published online June 25, 2023. doi:10.1016/S0140-6736(23)01185-6.