264-OR: Effect of Tirzepatide on Kidney Function in People with Excess Body Weight and Type 2 Diabetes—A Post-Hoc Analysis of the SURMOUNT-2 Trial

Tirzepatide (TZP), a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, has shown kidney protective effects in people with type 2 diabetes (T2D) at high risk for cardiovascular disease. In the SURMOUNT-2 (SM-2) trial in people with obesity or overweight with T2D, at 72 weeks TZP significantly reduced body weight by up to 15.7%, HbA1c by 2.22%, and systolic and diastolic blood pressure by 7.7mmHg and 2.9mmHg respectively. This post-hoc analysis assessed the potential impact of TZP vs PBO on kidney parameters in SM-2 trial participants. Data from all participants randomly assigned to treatment were included (pooled TZP [10 and 15 mg], N = 623; PBO, N = 315). Assessments included CKD-EPI creatinine-cystatin-C-based eGFR (Cr-Cys-C-eGFR), and urine albumin-to-creatinine ratio (UACR). The change from baseline to week 72 was analyzed using mixed models for repeated measures with on-treatment data. Baseline mean Cr-Cys-C-eGFR was 91.3±19.5 mL/min/1.73m². The estimated treatment difference (ETD) between pooled TZP groups and PBO on the change from baseline in Cr-Cys-C-eGFR was 0.0 mL/min/1.73m² (95% confidence interval [CI] -1.7, 1.7; p=0.993). TZP compared to placebo did not change Cr-Cys-C-eGFR at week 72 in participants with baseline Cr-Cys-C-eGFR <60 ml/min/1.73m2 (p=0.180) or ≥ 60 ml/min/1.73m2 (p=0.714). Baseline median UACR was 13.0 mg/g (interquartile range 6.0-35.0 mg/g). UACR significantly decreased with TZP vs. PBO (ETD -31.1 %, 95% CI -40.9, -19.7, p<0.001) and for those with baseline UACR ≥30 mg/g, the ETD was -55.2% (95% CI -68.5, -36.4; p<0.001). In this SM-2 trial population of participants with obesity or overweight with T2D and preserved eGFR at baseline, TZP reduced albuminuria without adversely affecting eGFR.