People With Lowest Physical Functioning Scores Showed Greatest Improvement After Tirzepatide Treatment.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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) 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: SURMOUNT-1, NCT04184622; SURMOUNT-3, NCT04657016; SURMOUNT-4, NCT04660643.