Head-to-Head Diabetes Drugs for Weight Loss: Tirzepatide Outperforms Semaglutide in New Study

A recent cohort study of adults with overweight or obesity revealed that most adults with obesity or overweight experienced 5% or greater weight loss with treatment; the benefit was greater with tirzepatide. The findings were published online in JAMA Internal Medicine.

Semaglutide, developed originally for type 2 diabetes management, has garnered attention for its remarkable weight loss effects. On the other hand, tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist has shown promising results in its own right.

Although semaglutide and tirzepatide were shown to reduce weight in randomized clinical trials, data is not yet available from head-to-head comparisons in populations with overweight or obesity. To fill this knowledge gap, Patricia J. Rodriguez, Truveta Inc, Bellevue, Washington, and colleagues aimed to compare on-treatment weight loss and rates of gastrointestinal adverse events (AEs) among overweight/obese adults receiving tirzepatide or semaglutide labeled for type 2 diabetes (T2D) in a clinical setting.

For this purpose, the researchers identified overweight/obese receiving semaglutide or tirzepatide between 2022 and 2023 using electronic health record (EHR) data linked to dispensing information from a collective of US healthcare systems. They assessed on-treatment weight outcomes through November 3, 2023.

Adults who were overweight or obese and had received regular care the year before starting treatment had not previously used any glucagon-like peptide 1 receptor agonists, received a prescription within 60 days before starting treatment, and recorded baseline weight measurements were included in the study. The analysis was finalized on April 3, 2024.

Weight changes during treatment were evaluated in a group matched by propensity scores. The study assessed the likelihood of achieving weight loss of 5% or more, 10% or more, and 15% or more, as well as the percentage change in weight at 3, 6, and 12 months. Additionally, the study compared the risks of gastrointestinal adverse events.

The study led to the following findings:

• Among 41 222 adults meeting the study criteria (semaglutide, 32 029; tirzepatide, 9193), 18 386 remained after propensity score matching. The mean age was 52.0 years, 70.5% were females. The mean baseline weight was 110 kg.
• Follow-up ended with discontinuation for 55.9% of patients receiving tirzepatide and 52.5% receiving semaglutide.
• Patients receiving tirzepatide were significantly more likely to achieve weight loss (≥5%; hazard ratio [HR], 1.76; HR, 2.54; HR, 3.24).
• On-treatment changes in weight were larger for patients receiving tirzepatide at three months (difference, −2.4%), six months (difference, −4.3%), and 12 months (difference, −6.9%).
• Rates of gastrointestinal AEs were similar between groups.

In conclusion, overweight/obese individuals treated with tirzepatide were significantly more likely to achieve clinically meaningful weight loss and larger body weight reductions compared with those treated with semaglutide. The researchers observed consistent treatment effect estimates in subgroups with and without T2D.

"There is a need for future work to compare the effect of semaglutide and tirzepatide on other key endpoints (e.g., reduction in major adverse cardiovascular events)," the researchers wrote.

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