Abstract 15280: Does Weight Reduction Drive the Reduction in Blood Pressure in People Living With Obesity Treated With Tirzepatide?: Insights From SURMOUNT-1 Study

Background: Tirzepatide (TZP) is a GIP/GLP-1 receptor agonist indicated for the treatment of type 2 diabetes and in development for chronic weight management. In SURMOUNT-1, in participants with obesity or overweight, TZP 5, 10 and 15 mg reduced body weight (-15 to -20.9%), SBP (-7 to -8.2 mmHg) and DBP (-4.6 to -5.5 mmHg) after 72 weeks of intervention.

Aim: To assess the effects of TZP on SBP and DBP by baseline (BL) blood pressure (BP) levels and to evaluate the contribution of weight loss to the effect.

Methods: Adults with a BMI ≥30 kg/m2, or ≥27 kg/m2 and ≥ 1 diagnosed weight-related complication, excluding diabetes, received TZP (5, 10, or 15 mg) or placebo (PBO) for 72 weeks. Participants with a valid BL BP value and ≥1 post-BL value were included in the analysis using the efficacy analysis set (excluding off-treatment data). Changes from BL through 72 weeks in SBP and DBP were compared between pooled TZP doses and PBO with mixed models for repeated measures (MMRM) by BL BP levels. The proportion of participants reaching recommended BP thresholds was also evaluated. Post-hoc mediation analyses evaluated the weight-loss dependent, and independent, effects of TZP in SBP and DBP reduction.

Results: Regardless of BL BP values, pooled TZP showed consistent SBP and DBP reduction at 72 weeks from BL, relative to PBO (Figure 1a). At 72 weeks, a greater proportion of TZP treated participants achieved recommended SBP and DBP levels than participants treated with PBO (Figure 1b), nearly doubling the proportion of patients with normal BP values. Changes in body weight with SBP (r=0.24) and DBP (r=0.24) were moderately correlated. Mediation analysis indicated that SBP and DBP reductions were primarily mediated through weight loss (77% and 99% respectively).

Conclusions: Effects of TZP on blood pressure were consistent regardless of SBP or DBP values at BL, increasing the proportion of patients reaching normal BP levels. Reductions in SBP and DBP were substantially mediated by weight reduction.