Impact of tirzepatide on systemic arterial stiffness assessed by cardio-ankle vascular index in individuals with obesity complicated by type 2 diabetes: A retrospective cohort study in Japan.

BACKGROUND: Tirzepatide, a multi-agonist incretin agent that targets body weight and metabolic parameters, has stronger weight reduction and glycemic control effects than existing agents. This study aimed to elucidate the effects of tirzepatide on vascular function in individuals with obesity complicated by type 2 diabetes (T2D). METHODS: This retrospective observational cohort study evaluated the effects of weekly tirzepatide (5-15 mg, median treatment duration 12.7 months) on vascular function and body composition in 24 individuals [45.8% male, median 48.6 years, body mass index (BMI) 32.3 kg/m] with obesity and T2D. Sixteen individuals (66.7%) were switched from glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Vascular function was assessed using the cardio-ankle vascular index (CAVI), and body composition was evaluated using skeletal muscle index (SMI) and body fat index (BFI) measured by InBody720. RESULTS: Tirzepatide treatment significantly decreased CAVI (post-treatment to baseline: median 8.5 to 7.8) accompanied by significant reductions in BMI (mean 33.8 to 31.8 kg/m), SMI (median 11.4 to 10.7 kg/m), BFI (median 12.8 to 11.3 kg/m) and glycemic parameters (including HbA1c: median 6.6 to 5.6%). The urinary albumin/creatinine ratio (UACR) tended to decrease with tirzepatide (median 11.9 to 7.2 mg/gCr,  = 0.067), and change in (Δ)UACR showed a trend of positive correlation with ΔCAVI (  = 0.403,  = 0.057). BMI reduction was greater ( = 0.040) and CAVI reduction tended to be greater ( = 0.089) at higher tirzepatide doses (10 and 15 mg) than at lower doses (5 and 7.5 mg). Prior GLP-1 RA use did not affect tirzepatide efficacy. Baseline SMI, but not BFI, correlated significantly and negatively with ΔCAVI (  = -0.424). CONCLUSION: Tirzepatide may dose-dependently reduce body weight and CAVI, contributed by decreased UACR and relatively high baseline SMI. Although tirzepatide is expected to improve kidney and vascular dysfunction in individuals with obesity complicated by T2D, careful attention to body composition is warranted.