Tirzepatide may reduce major kidney events in T2D patients with CVD, CKD

The use of tirzepatide appears to reduce decline in kidney function, prevent albuminuria progression, and lower the risk of the composite kidney outcome compared with dulaglutide in patients with type 2 diabetes (T2D), atherosclerotic cardiovascular disease (ASCVD), and very high-risk chronic kidney disease (CKD), reports a study presented at Kidney Week 2025.

The composite kidney events outcome was as follows: onset of macroalbuminuria, a 50-percent or greater decline in estimated glomerular filtration rate (eGFR), end-stage kidney disease, or kidney-related death.

“In SURPASS-CVOT, among patients with T2D and ASCVD, tirzepatide reduced eGFR decline, albuminuria progression, and the risk of the composite major kidney outcome compared with dulaglutide,” said lead author Dr Sophia Zoungas, academic director of the Monash University Clinical Trials Centre and head of the School of Public Health and Preventive Medicine in Melbourne, Australia.

This study included a total of 1,241 patients with very high-risk CKD (mean age 68.5 years, mean BMI 33.0 kg/m2, mean HbA1c 8.6 percent, mean duration of diabetes 19.2 years), of whom 24.9 percent had been treated with SGLT2 inhibitors. [ASN 2025, abstract FR-OR087]

At 36 months, changes in eGFR were ‒3.0 for tirzepatide and ‒7.2 for dulaglutide, with a significant difference of 4.1 mL/min per 1.73 m². Moreover, the percent changes in urine albumin-creatinine ratio (UACR) were ‒45.6 and ‒28.0, respectively, with a significant difference of ‒24.6 g/kg.

Notably, treatment with tirzepatide led to a 33-percent lower risk of the four-component composite kidney outcome than dulaglutide (16.7 percent vs 23.0 percent; hazard ratio, 0.67, 95 percent confidence interval, 0.52‒0.87; p=0.002).

Safety profile

Treatment discontinuation was comparable between the tirzepatide and dulaglutide groups (30.0 percent vs 28.2 percent), as were the rates of any treatment-emergent adverse events (AEs; 95.7 percent vs 94.7 percent) and serious AEs (60.8 percent vs 63.5 percent). [https://www.renalandurologynews.com/reports/chronic-kidney-disease-ckd-tirzepatide-dulaglutide-reduce-major-kidney-events/]

However, the use of tirzepatide resulted in more gastrointestinal AEs (64.6 percent vs 58.5 percent) and severe gastrointestinal events (7.5 percent vs 5.3 percent). The most common AEs among users of tirzepatide were nausea, vomiting, and diarrhoea.

“We think that this data adds to the growing body of evidence that these agents are kidney protective and really should be part of the contemporary management and prevention of CKD,” Zoungas said. “Within that [GLP1-RA] class, dual agonists are likely to have greater effects.”

Methods

Using the KDIGO 2025 guideline, very high-risk CKD was defined as eGFR <30 mL/min/1.73 m² or eGFR ≥30 to <45 mL/min/1.73 m² and micro/macroalbuminuria or eGFR ≥45 to <60 mL/min/1.73 m² and macroalbuminuria.

Zoungas and her team assessed changes in eGFR and UACR from baseline to 36 months using analysis of covariance models, with treatment, SGLT2 inhibitor use at baseline, country, and baseline values as fixed covariables, with multiple imputation of missing data. They also used Cox proportional hazards models, stratified by SGLT2 inhibitor use at baseline, to analyse the composite kidney outcome.

“Tirzepatide has been shown to improve glycaemic control and weight loss compared with GLP-1 RAs,” Zoungas said. “Benefits have also been observed for atherogenic lipoproteins, improvements in blood pressure, highly sensitive C-reactive protein, albuminuria, and kidney function.” [https://www.renalandurologynews.com/reports/chronic-kidney-disease-ckd-tirzepatide-dulaglutide-reduce-major-kidney-events/]