#VisualAbstract:Oral semaglutide effectively reduces bodyweight in non-diabetic adults with obesity

1. The semaglutide 50 mg group saw a 15.1% reduction in body weight at 68 weeks compared to 2.4% in the placebo group.

2. Any-grade adverse events were more common among the semaglutide group with the most common being mild-to-moderate severity gastrointestinal symptoms.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Patients with overweight or obese body-mass-indices (BMIs) often struggle with weight management on conservative therapy. In such patients, glucagon-like peptide-1 (GLP-1) agonists, such as semaglutide, may be helpful in lowering body weight while also reducing blood glucose. Although the role of semaglutide in patients with type 2 diabetes is well-established, its use among adults without type 2 diabetes mellitus remains unclear. This randomized controlled trial aimed to assess the safety and efficacy of semaglutide versus placebo for treating overweight or obesity in non-diabetic adults. The primary outcome of this study was percentage change in body weight from baseline to 68 weeks, while the key secondary outcome was the proportion of patients achieving a body weight reduction ≥ 5%. According to study results, oral semaglutide led to a significant reduction in body weight compared to placebo. Although this study was well done, it was limited by a high occurrence of medication-related adverse events.

Click to read the study in The Lancet

Relevant Reading: Once-Weekly Semaglutide in Adults with Overweight or Obesity

In-depth [randomized-controlled trial]: Between Sept 13 and Nov 22, 2021, 709 patients were screened for eligibility across 50 outpatient clinics in 9 countries. Included were patients with a BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with complications, and no type 2 diabetes. Altogether, 667 patients (334 in semaglutide 50 mg and 333 in placebo) were included in the final analysis. The primary outcome of mean change in body weight was significantly greater in the semaglutide 50 mg group (-15.1%, standard error [SE] 0.5) versus placebo (-2.4%, SE 0.5, p<0.0001). This was also the case for the proportion of patients who reached bodyweight reduction ≥ 5% (85% semaglutide 50 mg vs. 26% placebo, odds ratio [OR] 12.6, 95% confidence interval [CI] 8.5-18.7, p<0.0001). Adverse events, primarily gastrointestinal, were more common in the semaglutide group (80%) than placebo (46%). Overall, findings from this study suggest that semaglutide 50 mg leads to a clinically significant decrease in body weight among adults with overweight or obese BMIs and no type 2 diabetes.

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