Tirzepatide Slows Renal Decline in T2D Patients with CKD in First Analysis of Dual Agent on Kidney Function

_{Hiddo Lambers Heerspink, PhD, PharmD}

In a cohort of older adults with type 2 diabetes (T2D) and at elevated cardiovascular (CV) risk, the novel once-weekly drug tirzepatide significantly slowed progression of chronic kidney disease including rates of new onset macroalbuminuria.

The findings come from a prespecified exploratory analysis of the SURPASS-4 clinical trial presented at the 82nd Scientific Sessions of the American Diabetes Association.

Tirzepatide is a first-in-class, once-weekly injectable dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) mimetic approved in the US in May 2022 as an adjunct to diet and exercise to reduce hyperglycemia in adults with T2D. The new analysis is the first to explore the impact of the dual agent on kidney function in patients with T2D.

In the SURPASS-4 trial, part of the phase 3 SURPASS clinical trial program, tirzepatide led to superior reductions in A1c levels compared to titrated daily insulin glargine in patients with T2D and high CV risk who were inadequately controlled on oral antidiabetes treatments (median study duration 85 weeks).

The current analysis compared the effects on progression to prespecified kidney endpoints of tirzepatide and insulin glargine. The composite kidney outcome of interest was decline in estimated glomerular filtration rate (eGFR) ≥40% from baseline, renal death, progression to end-stage renal disease (ESRD), analyzed with and without new-onset macroalbuminuria.

Investigators analyzed data within the entire study population, and in subgroups defined by baseline SGLT2 inhibitor use, urine albumin-to-creatinine ratio (UACR) ≥30 mg/g, eGFR <60 mL/min/1.73m² and in those at high risk for kidney-related outcomes (eGFR <75 mL/min per 1.73 m² and macroalbuminuria, or eGFR <45 mL/min per 1.73 m²).

Total enrollment in SURPASS-4 was 1995 patients, with a mean age of 63.6 years. Mean measures at baseline for the group were HbA1c, 8.5%; eGFR, 81.3 mL/min per 1.73 m². Within the total group, 17% had eGFR <60 mL/min per 1.73 m², 28% had microalbuminuria (UACR 30-300 mg/g) and 8% had macroalbuminuria (UACR >300 mg/g).

WATCH: Dr Heerspink discusses the SURPASS-4 renal outcomes with Patient Care Online.

During follow-up of 104 weeks, tirzepatide-treated patients experienced significantly fewer renal outcomes versus insulin glargine with a hazard ratio of 0.59 (95% CI 0.43-0.80, P<.05) for the composite renal endpoint (eGFR decline ≥40%, baseline, renal death, progression to ESRD, new onset macroalbuminuria). Notably those treated with tirzepatide overall had significantly lower rates of new onset macroalbuminuria (HR 0.41, 95% CI 0.26-0.66, P<.05). In subgroup analysis, investigators found lower incidence of the composite renal outcome among tirzepatide-treated patients vs those on glargine regardless of background SLGT2 inhibitor treatment, over a range of albuminuria severity, and for those with moderately or severely reduced kidney function and at high risk for poor renal outcomes.

“With these exploratory findings of SURPASS-4, we are seeing the results of combined GIP/GLP-1 receptor agonists on the kidney function of patients with type 2 diabetes for the very first time,” said Hiddo L Heerspink, PhD, PharmD, University Medical Center Groningen, Netherlands. “The findings will be of interest to physicians treating people with diabetes who may have chronic kidney disease.”

Abstract: Heerspink HjL, Sattar N, Pavo I, et al. Effects of tirzepatide vs insuline glargine 100 U/mL on kidney outcomes in participants with type 2 diabetes in SURPASS-4. Poster presented at the 82ndScientific Sessions of the American Diabetes Association; June 3-7, 2022; New Orleans, LA.