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

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 m2) and stage G3b (eGFR 30 to <45 ml/min/1.73 m2). 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.