A comparison of the effects of tirzepatide and dulaglutide on major kidney events in people with type 2 diabetes: pre-specified exploratory analyses of the SURPASS-CVOT trial

Background In the SURPASS-CVOT trial, tirzepatide, a dual incretin agonist that targets the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, was shown to be non-inferior to dulaglutide for the primary composite cardiovascular outcome in people with type 2 diabetes and atherosclerotic cardiovascular disease. Here, we report the results of a pre-specified exploratory analysis of SURPASS-CVOT that aimed to assess major kidney events in the overall population, low-to-moderate-risk chronic kidney disease population, and high-risk chronic kidney disease population. Methods SURPASS-CVOT was a randomised, active comparator-controlled, double-blind trial that enrolled people with type 2 diabetes and atherosclerotic cardiovascular disease at 640 sites in 30 countries. Participants aged 40 years or older with type 2 diabetes and atherosclerotic cardiovascular disease, HbA 1c between 7% and 10·5%, and a BMI of 25 kg/m 2 or greater were randomly assigned 1:1 to once-weekly blinded subcutaneous injection of either tirzepatide up to 15 mg or dulaglutide 1·5 mg. Annual visits included assessment of serum creatinine, cystatin C, and urine albumin-to-creatinine ratio (UACR). High-risk chronic kidney disease was defined by an estimated glomerular filtration rate (eGFR) of 60 mL/min per 1·73 m 2 or greater and UACR greater than 300 mg/g; eGFR 45 mL/min per 1·73 m 2 to less than 60 mL/min per 1·73 m 2 and UACR greater than 30 mg/g; or eGFR less than 45 mL/min per 1·73 m 2 , with eGFR calculated with the CKD-Epidemiology Collaboration serum creatinine-cystatin C equation. The primary composite kidney outcome was time to first occurrence of persistent macroalbuminuria, persistent reduction in eGFR of 50% or greater, end-stage kidney disease (eGFR