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

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. Shifts in BMI categories (<25, 25 to <30, 30 to <35, 35 to <40, and ≥40 kg/m 2 ) 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. 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 2 ; SURMOUNT-4: -10.47 vs -5.20 kg/m 2 ). In the improved BMI category, tirzepatide treatment showed significant improvement in cardiometabolic parameters in both studies. 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.