Introduction: In SURMOUNT-1, treatment with once weekly GIP and GLP-1 receptor agonist tirzepatide resulted in substantial body weight reductions in people living with obesity. Hypothesis: This post hoc analysis assessed whether participants with obesity (body mass index [BMI] ≥30 kg/m 2 ) or overweight (BMI ≥27 kg/m 2 with at least one weight-related comorbid condition) who shifted to a lower BMI category had improved cardiometabolic factors. Methods: Change in BMI category (<25 kg/m 2 , 25 to <30 kg/m 2 , 30 to <35 kg/m 2 , 35 to <40 kg/m 2 , and ≥40 kg/m 2 ) from baseline to week 72 was assessed in participants from SURMOUNT-1 (N=2539) treated with tirzepatide or placebo. BMI shifts were grouped into “improved” (shift to at least one lower BMI category) or “stable” (no change) or “worse” (shift to a higher BMI category). Cardiometabolic parameters included waist circumference, fasting insulin, fasting glucose, HbA1c, blood pressure, and lipid profile. Results: In SURMOUNT-1, most participants demonstrated improved BMI with tirzepatide treatment (N=1457, 76.8%) while some had stable BMI (N=422, 22.3%) or worsened BMI (N=5, 0.3%) (Table). Furthermore, 38.1% improved by ≥2 BMI categories. Most placebo-treated participants had stable BMI. Compared to those with stable or worsened BMI, participants with improved BMI demonstrated greater improvement in cardiometabolic risk factors, including decreases from baseline in waist circumference, fasting insulin, fasting glucose, HbA1c, systolic and diastolic blood pressure, triglycerides, and cholesterol (non-HDL-c, and LDL-c) and increases from baseline in HDL-c. Conclusions: Substantial shifts to lower BMI categories were observed among tirzepatide-treated people living with obesity or overweight in SURMOUNT-1. Improved BMI and accompanying cardiometabolic risk factors with tirzepatide may lower further cardiovascular outcomes. Relevant outcomes trials are ongoing.
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