Trial results comparing tirzepatide to semaglutide in participants with obesity or overweight were posted on ClinicalTrials.gov on 2025-11-26. The study showed that participants treated with tirzepatide 15 mg achieved a least squares mean body weight reduction of -20.2%, compared to -13.7% for those on semaglutide 2.4 mg.
Background
The study (NCT05822830) evaluated the efficacy and safety of tirzepatide compared with semaglutide in adult participants who have obesity or are overweight with weight-related comorbidities, but without Type 2 Diabetes.
Trial design
The study (NCT05822830) was a Phase 3b, completed trial that enrolled 751 participants. It investigated tirzepatide compared to semaglutide in adult participants with obesity or who were overweight with weight-related comorbidities, excluding those with Type 2 Diabetes. The study duration was approximately 74 weeks.
Key results
The trial results demonstrated differences in weight reduction and other metrics between the tirzepatide and semaglutide groups:
- For "Percent Change From Baseline in Body Weight":
- Participants receiving tirzepatide 15 mg or MTD achieved a least squares mean reduction of -20.2% (Standard Error: 0.59).
- Participants receiving semaglutide 2.4 mg or MTD achieved a least squares mean reduction of -13.7% (Standard Error: 0.59).
- For "Change From Baseline in Waist Circumference in Centimeter":
- Participants receiving tirzepatide 15 mg or MTD achieved a least squares mean reduction of -18.4 centimeters (Standard Error: 0.61).
- Participants receiving semaglutide 2.4 mg or MTD achieved a least squares mean reduction of -13.0 centimeters (Standard Error: 0.66).
Regarding the percentage of participants achieving specific body weight reductions:
- For ≥10% Body Weight Reduction: 87.7% of participants on tirzepatide 15 mg or MTD achieved this, compared to 66.7% on semaglutide 2.4 mg or MTD.
- For ≥15% Body Weight Reduction: 71.7% of participants on tirzepatide 15 mg or MTD achieved this, compared to 45.0% on semaglutide 2.4 mg or MTD.
- For ≥20% Body Weight Reduction: 55.0% of participants on tirzepatide 15 mg or MTD achieved this, compared to 31.1% on semaglutide 2.4 mg or MTD.
- For ≥25% Body Weight Reduction: 36.5% of participants on tirzepatide 15 mg or MTD achieved this, compared to 18.6% on semaglutide 2.4 mg or MTD.
Key analyses reported least squares mean differences between the tirzepatide and semaglutide groups:
- For "Percent Change From Baseline in Body Weight", the least squares mean difference was -6.5 (95.0% CI: -8.1 to -4.9), indicating greater reduction with tirzepatide.
- Additional analyses reported least squares mean differences of -5.4 (95.0% CI: -7.1 to -3.6), -2.6 (95.0% CI: -3.2 to -1.9), and -6.4 (95.0% CI: -8.0 to -4.7).
What this means
The results of this Phase 3b trial indicate that tirzepatide demonstrated greater efficacy in reducing body weight and waist circumference compared to semaglutide in adults with obesity or overweight and weight-related comorbidities. A higher percentage of participants on tirzepatide achieved clinically significant weight loss thresholds (e.g., ≥10%, ≥15%, ≥20%, ≥25%). These findings provide important comparative data for clinicians and patients considering treatment options for weight management.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05822830, titled "A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight With Weight Related Comorbidities," were posted on 2025-11-26 on clinicaltrials.gov.