Shifts in body mass index category with tirzepatide and associated changes in cardiometabolic risk factors in people with obesity: a post hoc analysis from the SURMOUNT-1 and SURMOUNT-4 trials.

OBJECTIVE: Obesity is a chronic disease that results in increased morbidity and mortality if left untreated. Tirzepatide is a glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist approved in the United States for the treatment of type 2 diabetes, obesity, and obstructive sleep apnea. These post hoc analyses assessed the cardiometabolic risk factors of participants with obesity or overweight treated with tirzepatide who shifted to a lower body mass index (BMI) category. METHODS: Shifts in BMI categories (<25, 25 to <30, 30 to <35, 35 to <40, and ≥40 kg/m) from baseline to Week 72 (SURMOUNT-1) and Week 88 (SURMOUNT-4) were assessed. BMI shifts were classified as improved (shift to ≥1 lower category) or not improved (no change/shift to a higher category). Changes from baseline in weight, waist circumference, fasting insulin, fasting glucose, glycated hemoglobin, vitals, blood pressure, and lipid profile were measured. RESULTS: Improvement in BMI category from baseline occurred in 81.8 % of participants treated with tirzepatide in SURMOUNT-1 and 91.6 % in SURMOUNT-4. Among these participants, mean BMI reductions were greater than in those without improvement (SURMOUNT-1: -8.90 vs -3.65 kg/m; SURMOUNT-4: -10.47 vs -5.20 kg/m). In the improved BMI category, tirzepatide treatment showed significant improvement in cardiometabolic parameters in both studies. CONCLUSION: In these post hoc analyses, the majority of tirzepatide-treated participants with obesity or overweight shifted to lower BMI categories. Tirzepatide treatment was associated with significantly improved cardiometabolic risk factors in participants who shifted to a lower BMI category, which may positively impact long-term cardiovascular outcomes.