Comparing Semaglutide vs Tirzepatide for Weight Loss in Adults with Obesity: JAMA Study

In a study published in the journal JAMA Internal Medicine, researchers analysed how weight loss differs between patients receiving tirzepatide compared with semaglutide among a clinical population of adults with overweight or obesity.

Overweight and obesity are common conditions linked to higher risks of various health issues and early death. Traditional weight loss medications have been few, poorly tolerated, and only mildly effective. However, newer drugs like semaglutide, a GLP-1 receptor agonist, and tirzepatide, a dual GLP-1/GIP agonist, have shown significant weight loss benefits in clinical trials for people with obesity, with or without type 2 diabetes (T2D). While tirzepatide has been found to cause more weight loss than semaglutide in T2D patients, direct comparisons of their effectiveness in people with overweight or obesity are still lacking.

In this cohort study, researchers used electronic health records (EHR) to assess weight outcomes for adults with overweight or obesity who received semaglutide or tirzepatide between May 2022 and September 2023. They included adults with no prior use of GLP-1 receptor agonists, who had regular care in the year before starting the medication, and an available baseline weight. Participants had a BMI of 27 or higher or a diagnosis code for overweight or obesity.

Patients were classified as having type 2 diabetes (T2D) if they had a T2D diagnosis, were prescribed insulin or DPP-4 inhibitors, or had an HbA1c level of 7.5% or higher within the past two years. The study also reviewed patient demographics, clinical comorbidities, use of other antidiabetic medications, anti-obesity medications, and history of bariatric surgery.

The results showed that patients on tirzepatide had significantly more weight loss. At 3 and 12 months, those on tirzepatide experienced greater weight reduction. Among the matched group, 81.8% on tirzepatide vs. 66.5% on semaglutide achieved at least 5% weight loss, 62.1% vs. 37.1% achieved at least 10% weight loss, and 42.3% vs. 18.1% achieved at least 15% weight loss within a year. The hazard ratios for tirzepatide compared to semaglutide were 1.76 for 5% weight loss, 2.54 for 10% weight loss, and 3.24 for 15% weight loss.

The findings revealed that individuals with overweight or obesity treated with tirzepatide were significantly more likely to achieve clinically meaningful weight loss and larger reductions in body weight compared with those treated with semaglutide. Consistent treatment effect estimates were observed in subgroups with and without T2D. Future work is needed to compare the effect of tirzepatide and semaglutide on other key end points.

Reference: Rodriguez PJ, Goodwin Cartwright BM, Gratzl S, et al. Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity. JAMA Intern Med. Published online July 08, 2024. doi:10.1001/jamainternmed.2024.2525