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Semaglutide vs. Tirzepatide for Weight Loss in Adults
Quick Takes
- 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 semaglutide.
- Furthermore, consistent treatment effect estimates were observed in subgroups with and without T2D.
- Additional prospective studies are indicated to compare the effect of tirzepatide and semaglutide on hard clinical endpoints (i.e., reduction in MACE).
Study Questions:
What is the on-treatment weight change and what are the rates of gastrointestinal adverse events (AEs) among adults with overweight or obesity receiving tirzepatide or semaglutide for type 2 diabetes (T2D) in a clinical setting?
Methods:
The investigators conducted a cohort study of adults with overweight or obesity receiving semaglutide or tirzepatide identified using electronic health record data linked to dispensing information from a collective of US health care systems. On-treatment weight outcomes were assessed. Adults with overweight or obesity and regular care in the year before initiation, no prior glucagon-like peptide 1 receptor agonist use, a prescription within 60 days prior to initiation, and an available baseline weight were identified. The main outcomes and measures were on-treatment weight change in a propensity score-matched population, assessed as hazard of achieving ≥5%, ≥10%, and ≥15% weight loss, and percentage change in weight at 3, 6, and 12 months. Hazards of gastrointestinal AEs were compared.
Results:
Among 41,222 adults meeting the study criteria (semaglutide, 32,029; tirzepatide, 9,193), 18,386 remained after propensity-score matching. The mean [standard deviation (SD)] age was 52.0 (12.9) years, 12,970 were female (70.5%), 14,182 were White (77.1%), 2,171 Black (11.8%), 354 Asian (1.9%), 1,679 were of other or unknown race, and 9,563 (52.0%) had T2D. The mean (SD) baseline weight was 110 (25.8) kg. Follow-up was ended by discontinuation for 5,140 patients (55.9%) receiving tirzepatide and 4,823 (52.5%) receiving semaglutide. Patients receiving tirzepatide were significantly more likely to achieve weight loss (≥5%: hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.68-1.84; ≥10%: HR, 2.54; 95% CI, 2.37-2.73; and ≥15%: HR, 3.24; 95% CI, 2.91-3.61). On-treatment changes in weight were larger for patients receiving tirzepatide at 3 months (difference, -2.4%; 95% CI, -2.5% to -2.2%), 6 months (difference, -4.3%; 95% CI, -4.7% to -4.0%), and 12 months (difference, -6.9%; 95% CI, -7.9% to -5.8%). Rates of gastrointestinal AEs were similar between groups.
Conclusions:
The authors report that use of tirzepatide was associated with significantly greater weight loss than semaglutide.
Perspective:
This cohort study reports 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 semaglutide. Furthermore, consistent treatment effect estimates were observed in subgroups with and without T2D. No significant differences in the incidence of gastrointestinal AEs were observed. Additional prospective studies are indicated to compare the effect of tirzepatide and semaglutide on hard clinical endpoints (i.e., reduction in major adverse cardiovascular events [MACE]). The ongoing SURMOUNT-5 (Study of Tirzepatide in Participants With Obesity or Overweight With Weight Related Comorbidities) trial comparing tirzepatide to semaglutide in patients with overweight or obesity but without T2D will provide additional insight.
Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention
Keywords: Diabetes Mellitus, Obesity, Overweight
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