Comparative effectiveness of sodium‐glucose cotransporter‐2 inhibitors versus glucagon‐like peptide‐1 receptor agonists in patients with type 2 diabetes and mild/moderate chronic kidney disease

Abstract Aim To determine the comparative effectiveness regarding major cardiovascular events of glucagon‐like peptide‐1 (GLP‐1) receptor agonists and sodium‐glucose cotransporter‐2 (SGLT‐2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Materials and Methods We assembled a cohort of commercially insured adult patients with T2DM in the United States (derived from Optum Clinformatics DataMart 2003‐2021) who were new users of GLP‐1 receptor agonists or SGLT‐2 inhibitors. We compared risks of non‐fatal myocardial infarction or stroke in patients with and without CKD, and further categorized by CKD stage: stages G1 or G2 [estimated glomerular filtration rate (eGFR) ≥60 ml/min] and A2 (urine albumin to creatinine ratio 30 to <300 mg/g) or A3 (urine albumin to creatinine ratio ≥300 mg/g), stage G3a (eGFR 45 to <60 ml/min/1.73 m 2 ) and stage G3b (eGFR 30 to <45 ml/min/1.73 m 2 ). We used proportional hazards regression after inverse probability of treatment weighting to compute hazard ratios and 95% confidence intervals. Results After accounting for the probability of treatment, patients with T2DM and CKD treated with SGLT‐2 inhibitors experienced a 14% lower risk of non‐fatal myocardial infarction or stroke (hazard ratio 0.86, 95% confidence interval 0.78‐0.94) relative to those treated with GLP‐1 receptor agonists. Conclusions Recognizing the potential for residual confounding, selection bias and immortal time bias, commercially insured patients in the United States with T2DM and CKD treated with SGLT‐2 inhibitors experienced significantly lower risks of non‐fatal myocardial infarction or stroke relative to those treated with GLP‐1 receptor agonists.