Kidney Parameters with Tirzepatide in Obesity with or without Type 2 Diabetes.
In a post hoc analysis of the SURMOUNT-1 and SURMOUNT-2 trials, tirzepatide was associated with reduced albuminuria at week 72 in people with overweight or obesity, with or without type 2 diabetes, and with no adverse change in eGFR.
Background
Tirzepatide is a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist that had previously shown kidney-protective effects in people with type 2 diabetes at high cardiovascular disease risk. This analysis asked whether a similar signal is present in people treated for overweight or obesity, with or without type 2 diabetes, by examining kidney function parameters in the SURMOUNT weight-management programme.
Study design
This was a post hoc analysis of two randomised trials. In SURMOUNT-1, participants with overweight or obesity without type 2 diabetes were randomised to tirzepatide 5 mg, 10 mg or 15 mg, or placebo. In SURMOUNT-2, participants with type 2 diabetes were randomised to tirzepatide 10 mg or 15 mg, or placebo. All tirzepatide dose groups were pooled within each trial. The assessments were change from baseline to week 72 in urine albumin-to-creatinine ratio (UACR) and in eGFR, with eGFR estimated three ways: creatinine-based, cystatin-C-based and creatinine-cystatin-C-based.
Key findings
SURMOUNT-1 included 2539 participants and SURMOUNT-2 included 938. Median baseline UACR was 6.0 mg/g (25th-75th percentile 4.0-11.0) in SURMOUNT-1 and 13.0 mg/g (6.0-35.1) in SURMOUNT-2. At week 72 the estimated UACR difference for tirzepatide versus placebo was -8.4% (95% CI -14.7 to -1.6) in SURMOUNT-1 and -31.1% (95% CI -40.9 to -19.7) in SURMOUNT-2. The effect was larger among participants with baseline UACR of at least 30 mg/g, where placebo-corrected changes at week 72 were -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. For eGFR in SURMOUNT-1, tirzepatide was associated with increases using cystatin-C-based and creatinine-cystatin-C-based equations, with mean differences versus placebo at week 72 of 3.2 ml/min per 1.73 m2 (95% CI 2.1-4.3) and 1.9 ml/min per 1.73 m2 (95% CI 0.9-2.9). In SURMOUNT-2 both tirzepatide and placebo groups showed increases in cystatin-C-based and creatinine-cystatin-C-based eGFR, with no between-group difference.
Clinical implications
In participants with overweight or obesity, with or without type 2 diabetes, tirzepatide was associated with reduced albuminuria and no adverse change in eGFR. The albuminuria signal was substantially larger in the diabetes cohort and in those who already had albuminuria at baseline, while the non-diabetes cohort showed only a modest overall reduction. Because this is a post hoc analysis of trials designed for weight outcomes, the findings describe an association rather than establishing a kidney-outcome benefit, and dedicated kidney endpoint trials remain the basis for any change in practice.
Category
Research
Source
J Am Soc Nephrol
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