Tirzepatide kidney benefit holds in cystatin C analysis of SURPASS-4
A cystatin C analysis suggests tirzepatide's kidney benefit is not just an artifact of weight loss, but it remains an intermediate marker rather than proof of fewer kidney failure events [1].
An analysis of the SURPASS-4 trial found that tirzepatide's apparent kidney benefit was still present when kidney function was measured with cystatin C, a blood marker that is not affected by muscle mass, according to results published June 2, 2023, in Diabetes Care [1].
The concern was measurement. Large weight loss can reduce muscle mass, and creatinine-based estimates of glomerular filtration rate (eGFR-creatinine) depend partly on muscle. If a drug causes weight loss, eGFR-creatinine can improve simply because less creatinine is being produced, even if kidney filtration has not changed. Cystatin C–based eGFR (eGFR-cystatin C) does not have that problem, the authors note [1].
The analysis pooled tirzepatide doses of 5, 10, and 15 mg and compared them with titrated insulin glargine in adults with type 2 diabetes and high cardiovascular risk. The primary outcome was change in eGFR from baseline at 52 weeks [1].
At one year, eGFR-creatinine fell by 2.5 mL/min/1.73 m2 with tirzepatide and by 3.9 mL/min/1.73 m2 with insulin glargine. The between-group difference was 1.4 mL/min/1.73 m2 (95% confidence interval 0.3 to 2.4), favoring tirzepatide [1]. Using cystatin C, eGFR fell by 3.5 mL/min/1.73 m2 with tirzepatide and by 5.3 mL/min/1.73 m2 with insulin glargine. The between-group difference was 1.8 mL/min/1.73 m2 (95% confidence interval 0.8 to 2.8), also favoring tirzepatide [1].
Baseline, one-year, and one-year change values correlated between the two eGFR measures, the authors report. Changes in eGFR did not correlate with body weight changes [1].
The authors conclude that tirzepatide slows the rate of eGFR decline and that the finding supports a kidney-protective effect [1].
Why it matters for patients
Kidney decline is a common and serious complication of type 2 diabetes. The new analysis addresses a specific doubt: whether tirzepatide's kidney signal was a measurement illusion caused by weight loss. The cystatin C results suggest the signal is not explained by muscle loss [1].
That said, eGFR is an intermediate marker. Whether tirzepatide reduces hard kidney outcomes such as kidney failure, dialysis, or transplant has not been reported [1]. The participants were adults with type 2 diabetes and high cardiovascular risk; results in other groups have not been reported in this analysis [1].
Several authors list Eli Lilly as their affiliation [1]. The paper is a post hoc analysis of the SURPASS-4 trial [1].
What happens next
The paper does not describe new trials or regulatory steps. Longer-term data on whether tirzepatide prevents kidney failure, dialysis, or other hard kidney outcomes have not been reported in this analysis [1].
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