A post hoc analysis of the SURPASS clinical trials has revealed significant renal protective effects of tirzepatide in adults with type 2 diabetes, particularly among those with existing chronic kidney disease (CKD).
The analysis, published in Diabetes Care, demonstrated that patients receiving tirzepatide (Mounjaro, Eli Lilly) across three dose levels - 5mg, 10mg, and 15mg - experienced substantial reductions in urine albumin-to-creatinine ratio (UACR) at approximately 40 weeks of treatment.
Dose-Dependent Renal Benefits
The study showed a clear dose-response relationship, with the 15mg dose achieving the most substantial benefits. Compared to control groups, UACR reductions were:
- 19.3% greater with 5mg tirzepatide
- 22% greater with 10mg tirzepatide
- 26.3% greater with 15mg tirzepatide All results achieved statistical significance (P < .001).
Enhanced Effects in CKD Patients
The renal benefits were particularly pronounced in patients with pre-existing kidney dysfunction. For patients with baseline UACR ≥30 mg/g, the reductions compared to controls reached:
- 31.3% with 5mg tirzepatide
- 42.2% with 10mg tirzepatide
- 47.3% with 15mg tirzepatide
In patients with estimated glomerular filtration rate below 60 mL/min/1.73 m2, the 15mg dose achieved an impressive 49.2% greater reduction in UACR compared to the control group.
Mechanism of Action
The analysis revealed tirzepatide's dual mechanism in improving kidney function. According to the researchers, 45.9% of the UACR reduction was mediated through improvements in HbA1c and body weight, while 54.1% was attributed to direct effects of the medication and other variables.
"Tirzepatide will likely slow the decline in kidney function and reduce the risk of kidney failure in patients with type 2 diabetes," stated Hiddo J. L. Heerspink, PhD, professor at the University Medical Center Groningen. He emphasized that previous meta-analyses have shown that therapies reducing UACR by at least 25% typically confer clinical benefit.
Study Context and Limitations
The analysis pooled data from five SURPASS trials, comparing tirzepatide against various controls including placebo, semaglutide, insulin degludec, and insulin glargine. The strongest effects were observed in trials comparing tirzepatide to placebo.
However, Dr. Heerspink noted that most participants in the SURPASS trials had preserved kidney function. He emphasized the need for additional studies specifically focusing on type 2 diabetes patients with CKD and incorporating longer follow-up periods to fully understand the medication's long-term renal benefits.
