A predictive model for estimating protection against CKD and CVD with SGLT2 inhibition in patients with diabetes

Abstract

Diabetes affects >450 million people worldwide. Elevated blood glucose caused by diabetes can lead to chronic kidney disease (CKD), which increases the risk of end‐stage kidney disease (ESKD) requiring dialysis or a kidney transplant. In type 2 diabetes (T2D), medications called sodium‐glucose cotransporter‐2 (SGLT2) inhibitors have become part of standard of the care for improving glycemic control by promoting urine glucose excretion. These drugs reduce urinary albumin excretion (quantified as urinary albumin‐to‐creatinine ratio, “UACR”, an effect linked with kidney protection), slow CKD progression and delay ESKD, with similar benefits in males and females. In people with T2D, SGLT2 inhibitors also reduce heart failure and cardiovascular events by 20‐40%. But in people with type 1 diabetes (T1D), there are no studies evaluating SGLT2 inhibitors in patients at the highest risk of ESKD or cardiovascular disease (CVD). Building on the benefits of SGLT2 inhibitors in people with T2D, we seek to evaluate the efficacy and mechanisms in people with T1D and CKD. We hypothesize that SGLT2 inhibition will slow loss of kidney function (glomerular filtration rate, or “GFR”) in people with T1D and CKD. To test that hypothesis, we analyze clinical data for a cohort of patients with diabetes and kidney disease, and identify key features that determine the rate of progression of CKD. We then develop personalized assessment tools that yield estimates for protection against CKD and CVD with SGLT2 inhibition in patients with T1D or T2D.