SGLTi Therapy Decreases Long-Term CVD and End-Stage Kidney Disease Risk in Type 1 Diabetes

Among patients with type 1 diabetes, sodium-glucose cotransporter inhibitor (SGLTi) therapy reduced risk for cardiovascular disease (CVD) and end-stage kidney disease (ESKD), especially among patients with albuminuria. These findings were published in the Journal of Diabetes and Its Complications.

Patients (N=3660) with type 1 diabetes (T1D) treated at the Steno Diabetes Center Copenhagen in Denmark between 2001 and 2016 were evaluated for 5- and 10-year risk rates for CVD and ESKD on the basis of clinical features. Risk rates were simulated using a Steno Type 1 Risk Engine approach.

The mean age of the study population is 48.3±11.4 years, 55.9% are men, they had been diagnosed with T1D at a median age of 27.2 (IQR, 15.3-37.9) years, mean hemoglobin A_1C (HbA_1C) is 8.4%±1.4%, 80.8% have normal to mildly elevated albuminuria, median estimated glomerular filtration rate (eGFR) was 94.7 (IQR, 82.0-106.0) mL/min/1.73m², and average total cholesterol was 5±1.0 mmol/L.

Five-year CVD estimated risk is 7.7% (95% CI, 3.9%-13.7%) without use of SGLTis. There is a 6.1% (95% CI, 5.9%-6.3%) reduction in CVD risk with SGLTi therapy (P <.001). SGLTi use decreases risk for CVD at 5 years by 11.1% among patients with albuminuria (P <.001), 6.2% among patients with HbA_1C of 7.7%-11% (P <.001), and 5.9% among patients with a BMI of 27 or higher (P <.001).

A similar trend is observed for the protective effect of SGLTi therapy on 10-year CVD risk. At 10 years, use of SGLTis reduces risk from 14.8% by 5.8% (P <.001) among all patients and by 10.2% among the albuminuria subgroup (P <.001), 5.8% among the elevated HbA_1C (P <.001) subgroup, and by 5.6% among the subgroup with elevated BMI (P <.001).

Five-year ESKD estimated risk is 0.7% (95% CI, 0.5%-1.1%) without SGLTi use with a 5.3% (95% CI, 5.1%-5.4%) reduction in risk with SGLTi therapy (P <.001). SGLTi therapy decreases risk for ESKD at 5 years by 7.6% among patients with albuminuria (P <.001), 5.3% among patients with HbA_1C of 7.7%-11% (P <.001), and 5.1% among patients with a BMI of 27 or higher (P <.001).

Similar trends are observed in a secondary analysis which assumes that patients with albuminuria had an eGFR change of 3.27 mL/min/1.73m² after SGLT2i therapy.

The major limitation of this study was not confirming risk reduction using an independent cohort.

“Our model thereby provides an estimate of benefit that needs to be interpreted in the context of known [diabetic ketoacidosis] associated with use of SGLTi in type 1 diabetes,” the study authors wrote. “Prospective randomized controlled trials in high risk patients with type 1 diabetes are needed to better elucidate the potential role of these therapies in patients at the highest risk of cardiorenal complications.”

Reference

Stougaard EB, Rossing P, Cherney D, Vistisen D, Persson F. Sodium–glucose cotransporter 2 inhibitors as adjunct therapy for type 1 diabetes and the benefit on cardiovascular and renal disease evaluated by Steno risk engines. J Diabetes Complications. Published online July 9, 2022. doi:10.1016/j.jdiacomp.2022.108257