People With Lowest Physical Functioning Scores Showed Greatest Improvement After Tirzepatide Treatment.
Li. Xuan X; Cao. Dachuang D; Sapin. Helene H; Wang. Fangyu F; Hunter Gibble. Theresa T; Raibulet. Nedina Kalezic NK; Denning. Max M; Kaplan. Lee M LM
Key Findings
- People with low baseline physical function had more obesity‑related health problems.
- Tirzepatide produced similar ~20% weight loss across all baseline fitness groups.
- Those with the worst starting physical function saw the biggest gains in physical function scores, beyond what weight loss alone would explain.
Practical Outcomes
- For biohackers aiming for both weight loss and better daily performance, tirzepatide appears effective regardless of starting fitness level. Using the trial‑based dosing schedule (up to 15 mg weekly) can yield substantial fat loss and notable functional gains, especially for those who feel sluggish or have limited mobility. The drug’s benefits may partly work independent of weight loss, so even modest weight drops can still improve strength and stamina.
Summary
The study shows that tirzepatide causes big weight loss (about 20% of body weight) in people with obesity, no matter how fit they start out, and it especially boosts physical function in those who were the least active or had the poorest health at the start. The improvement in function isn’t just from losing weight – there’s an extra benefit that seems to come directly from the drug.
Abstract
This post hoc analysis of SURMOUNT trials assessed the association of baseline physical function (PF) with obesity-related complications (ORCs), efficacy measures, and PF. The mechanism of tirzepatide-led improvements in PF was evaluated. Outcomes were assessed among participants (SURMOUNT-1 = 2539; SURMOUNT-3 = 579; SURMOUNT-4 = 670) grouped by baseline quartiles (Q) of SF-36v2 PF scores within study (higher scores = better PF). Least-squares mean changes from baseline in efficacy measures and PF were estimated using ANCOVA. Pearson's correlation between weight reduction and improvement in PF was calculated. In SURMOUNT-1, participants with lower baseline PF had more ORCs. Tirzepatide-treated participants showed similar reductions in weight (kg; -20.1% to -22.8%), waist circumference (-17.2 to -20.2 cm), and BMI (-7.2 to -9.0 kg/m<sup>2</sup>) across quartiles. Participants with lower baseline PF reported greater improvements in PF with tirzepatide (Q1 = 12.5; Q4 = -0.8). Results were similar in SURMOUNT-3 and SURMOUNT-4. A weak to mild correlation was noted between weight reduction and improved PF; the strength of correlation decreased from Q1 to Q4. Lower baseline PF was associated with a higher prevalence of ORCs. Patients taking tirzepatide experienced substantial weight loss, regardless of their baseline PF. Tirzepatide may improve PF through both weight loss-dependent and -independent mechanisms, especially in those with lower baseline PF. ClinicalTrials.gov identifiers: SURMOUNT-1, NCT04184622; SURMOUNT-3, NCT04657016; SURMOUNT-4, NCT04660643.
Study Information
pubmed
2025
2025-11-04T00:00:00.000Z
10.1002/oby.70067
33