Kidney Parameters with Tirzepatide in Obesity with or without Type 2 Diabetes

Key Points People with obesity and/or type 2 diabetes are at higher risk of progressive kidney function loss. We assessed the association of tirzepatide use with kidney function parameters in people with overweight/obesity with or without type 2 diabetes. Tirzepatide treatment was associated with urine albumin-to-creatinine reduction after 24 weeks, which was sustained through week 72, and no change in eGFR. Background Tirzepatide, a once-weekly, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, showed kidney-protective effects in people with type 2 diabetes at high cardiovascular disease risk. In this post hoc analysis of the SURMOUNT-1 and SURMOUNT-2 trials, we assessed the association of tirzepatide use with kidney function parameters in people with overweight/obesity with or without type 2 diabetes. Methods In SURMOUNT-1, participants with overweight or obesity without type 2 diabetes were randomized to tirzepatide 5, 10, and 15 mg or placebo. In SURMOUNT-2, participants with type 2 diabetes were randomized to tirzepatide 10 and 15 mg or placebo. For this analysis, all tirzepatide groups were pooled in each trial. Assessments included change from baseline to week 72 for urine albumin-to-creatinine ratio (UACR) and eGFR. eGFR was assessed using creatinine-based eGFR, cystatin-C–based eGFR, and creatinine-cystatin-C–based eGFR (Cr-Cys-C-eGFR). Results In SURMOUNT-1 ( N =2539) and SURMOUNT-2 ( N =938), the median (25th–75th percentile) baseline UACR was 6.0 (4.0–11.0) mg/g and 13.0 (6.0–35.1) mg/g, respectively. UACR estimated difference for tirzepatide versus placebo, at week 72 was−8.4% (95% confidence interval [CI], −14.7 to −1.6) for SURMOUNT-1 and −31.1% (95% CI, −40.9 to −19.7) for SURMOUNT-2. The UACR change was more pronounced among participants with baseline UACR ≥30 mg/g with placebo-corrected changes from baseline at week 72 of −42.3% (95% CI, −60.8 to −15.0) in SURMOUNT-1 and −55.2% (95% CI, −68.5 to −36.4) in SURMOUNT-2, respectively. In SURMOUNT-1, tirzepatide was associated with increased eGFR based on cystatin-C–based eGFR or Cr-Cys-C-eGFR estimation equations, with mean differences versus placebo at week 72 of 3.2 ml/min per 1.73 m 2 (95% CI, 2.1 to 4.3) and 1.9 ml/min per 1.73 m 2 (95% CI, 0.9 to 2.9), respectively. In SURMOUNT-2 at week 72, increases in both tirzepatide and placebo groups were observed for Cys-C or Cr-Cys-C-eGFR, with no between-group differences. Conclusions In participants with obesity/overweight with or without type 2 diabetes, tirzepatide was associated with reduced albuminuria without adverse changes in eGFR. Clinical Trial registry name and registration number: SURMOUNT-1: NCT04184622; SURMOUNT-2: NCT04657003.