Abstract
Recent clinical trials suggest benefit of anti-hyperglycemic drugs on kidney outcomes. However, there is a paucity of information available on the real-world impact.We aimed to study the real-world impact of anti-hyperglycemic drugs (metformin, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1receptor (GLP-1R) agonists) using a cohort of patients with incident diabetes derived from the Alberta Tomorrow Project (ATP) database. A retrospective cohort was created from the ATP database using administrative data from October 1, 2000, to March 31, 2021. We examined the effect of anti-hyperglycemic medications including metformin (as a control), SGLT-2 inhibitors, DPP-4 inhibitors, and GLP-1R agonists on a composite kidney outcome including chronic kidney disease, kidney failure, dialysis, kidney transplant, and kidney-related death using a Cox-regression analysis. The study included 3001 patients with an incident diagnosis of diabetes. The average follow-up was 6.7 ± 4.6 years after diagnosis, and 628 (20.9%) patients reached the composite outcome with a mean of 5.6 ± 4.2 years to the first event. A total of 1749 (58.8%) patients were on metformin, 360 (12.0%) on SGLT-2 inhibitors, 313 (10.4%) on DPP-4 inhibitors, and 188 (6.3%) on GLP-1R agonists. Only the patients prescribed SGLT-2 inhibitors had a significant reduction in the composite outcome (hazard ratio (HR) 0.23, 95% CI 0.09-0.62, P-value = .003), and a dose-related effect was observed. Our study has shown that SGLT-2 inhibitors result in significant reduction of composite kidney outcomes, including chronic kidney disease, suggesting a renally protective effect over long term.