Long-Term Mortality and SGLT2 Inhibitors in Type 2 Diabetes with and without Renal Impairment: An Observational Cohort Study

Aim: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have emerged as a vital part of management of type 2 diabetes, as they have been shown to have both cardiovascular and renal benefits along with an improved survival rate in several randomized clinical trials. We designed a retrospective cohort study to investigate the impact of SGLT2 inhibitors on mortality among type 2 diabetes patients. Methods: Patients with type 2 diabetes who presented to the Dasman Diabetes Institute in Kuwait were followed from January 1st, 2015, until January 20th, 2023. To control for non-random allocation of SGLT2 inhibitors and measured confounders, we performed oneto-one propensity score matching and evaluated outcomes in the matched cohorts using a Cox proportional hazards model. The primary treatment variable was SGLT2 inhibitor use; time to mortality from any cause was used as the outcome of interest. Results: 1,551 patients were taking SGLT2 inhibitors, and 1,687 patients were not. After propensity score matching, 845 patients were on SGLT2 inhibitors, and 845 patients were not. In post-matching analysis, all-cause mortality was higher among patients who did not take SGLT2 inhibitors compared to patients taking SGLT2 inhibitors (5.2 vs. 2.1%, p = 0.0012). The hazard ratio of all-cause mortality in patients taking SGLT2 inhibitors was 0.42 (95% confidence interval [95% CI], 0.24 0.72). Additional adjustment of matching factors did not change the results. Conclusion: This observational study demonstrated substantial long-term reduction in mortality risk among patients with type 2 diabetes treated with SGLT2 inhibitors. This is irrespective of the stage of their renal diseases or GLP1 agonist.