Summary:
In adults with obesity or overweight without type 2 diabetes from SURMOUNT-5, tirzepatide at maximum tolerated dose for 72 weeks showed similar physical health improvements with greater General Health domain improvement (5.45 vs 4.20, p=0.003) compared to semaglutide, though neither treatment significantly improved Mental Component Summary scores.
| PICO | Description |
|---|---|
| Population | Adults with obesity or overweight without type 2 diabetes from the SURMOUNT-5 trial who received ≥1 dose of tirzepatide or semaglutide at maximum tolerated doses. |
| Intervention | Tirzepatide at maximum tolerated dose for 72 weeks. |
| Comparison | Semaglutide at maximum tolerated dose for 72 weeks. |
| Outcome | Both treatments improved Physical Component Summary (p<0.001). Tirzepatide showed greater General Health improvement (5.45 vs 4.20, p=0.003). In limited physical function subgroup, tirzepatide superior for PCS, PF, and GH (p≤0.025). No significant MCS improvement for either. Greater weight loss associated with better physical outcomes. |
Clinical Context
Obesity significantly impairs health-related quality of life (HRQoL), particularly physical functioning, mobility, and self-perception of health. While weight loss interventions aim to improve health outcomes, the impact on patient-reported quality of life is equally important for treatment success and adherence. Understanding how different anti-obesity medications affect HRQoL helps inform treatment selection.
SURMOUNT-5 was the first head-to-head trial comparing tirzepatide and semaglutide for obesity treatment. The primary results showed tirzepatide achieved significantly greater weight loss than semaglutide. This prespecified analysis examines whether the weight loss differential translates to differences in patient-reported HRQoL outcomes.
The SF-36v2 is a validated instrument measuring eight health domains and two summary scores (Physical Component Summary and Mental Component Summary). Understanding which specific domains improve—and whether improvements differ between treatments—provides clinically actionable information for patient counseling and treatment selection.
Clinical Pearls
1. Physical Health Improves with Both Treatments: Both tirzepatide and semaglutide significantly improved Physical Component Summary scores from baseline (p<0.001), confirming that effective weight loss improves physical functioning regardless of specific agent used.
2. General Health Advantage for Tirzepatide: Tirzepatide showed significantly greater improvement in General Health perception (5.45 vs 4.20 points, p=0.003). General Health captures patients’ overall assessment of their health status, suggesting tirzepatide’s greater weight loss translates to more noticeable subjective health improvement.
3. Greater Benefits in Functionally Limited Patients: Patients with limited baseline physical function showed significantly greater improvements in Physical Component Summary, Physical Functioning, and General Health with tirzepatide versus semaglutide. This suggests tirzepatide may be particularly beneficial for patients with more severe functional impairment from obesity.
4. Mental Health Not Significantly Improved: Neither treatment significantly improved Mental Component Summary scores from baseline. This important finding suggests that while physical health improves with weight loss, mental health domains (including mental health, social functioning, and emotional role limitations) may require additional interventions beyond pharmacotherapy.
Practical Application
When counseling patients about anti-obesity medication options, explain that both tirzepatide and semaglutide improve physical quality of life. For patients with significant baseline physical limitations or those prioritizing subjective health perception, tirzepatide may offer advantages aligned with its greater weight loss efficacy.
Set appropriate expectations for mental health outcomes—while physical functioning improves, depression, anxiety, and emotional well-being may not automatically improve with weight loss alone. Patients with mental health concerns should receive appropriate psychological support in conjunction with obesity treatment.
The dose-response relationship between weight loss and HRQoL improvement suggests that achieving maximal weight loss optimizes quality of life benefits. Support patients in reaching and maintaining maximum tolerated doses of whichever agent is selected.
Broader Evidence Context
This analysis extends SURMOUNT-5’s primary weight loss findings to patient-reported outcomes. Previous trials of both tirzepatide (SURMOUNT-1 through 4) and semaglutide (STEP trials) have shown HRQoL improvements, but this is the first head-to-head comparison in the same trial population.
The lack of mental health improvement aligns with other obesity treatment literature suggesting that psychological benefits of weight loss are complex and variable. Some patients experience improved mental health while others may face challenges including body image adjustment and weight regain anxiety.
Study Limitations
On-treatment analysis may introduce bias if treatment discontinuation differed between groups. SF-36v2 is generic and may miss obesity-specific quality of life concerns captured by disease-specific instruments. Post hoc subgroup analysis of limited physical function patients should be interpreted cautiously. 72-week duration may not capture long-term HRQoL trajectory. Sample size for some subgroups may be limited.
Bottom Line
Both tirzepatide and semaglutide improve physical health-related quality of life in adults with obesity, with tirzepatide showing significantly greater improvement in general health perception and more pronounced benefits in patients with limited baseline physical function, while neither treatment significantly improved mental health component scores.
Source: Shukla AP, et al. “Improved health-related quality of life with tirzepatide versus semaglutide in adults with obesity or overweight from the SURMOUNT-5 trial.” Diabetes Obes Metab. 2026;28(1):452-462. Read article
