SGLT2 inhibitors reduce adverse kidney and cardiovascular events in patients with advanced diabetic kidney disease: A population-based propensity score-matched cohort study

Background: There were limited data on the efficacy and safety profile on use of sodium-glucose co-transporter 2 receptor (SGLT2) inhibitors in diabetic patients with advanced chronic kidney disease (CKD). We aimed to evaluate the efficacy, in terms of improvement in glycemic profile, kidney function, prevention of adverse kidney and cardiovascular events, and the safety profile of SGLT2 inhibitors in a group of diabetic patients at CKD stage 3B-5 from a real-world population-based cohort.Methods: We performed a retrospective observational cohort study of type 2 diabetic patients at CKD stage 3B-5 who received SGLT2 inhibitors as compared to control from 1 January 2015 through 31 December 2021. Pro-pensity score assignment by logistic regression and matching with control by the nearest score at 1:3 ratio was done. All patients were followed for 1 year. Outcomes were kidney-related adverse events and major adverse cardiovascular events (MACE), change in estimated glomerular filtration rate (eGFR), glycemic control, and side effects profiling.Results: We analyzed 1,450 SGLT2 inhibitor users. They had significantly lower rates of kidney-related adverse events (7.7 % versus 24.1 %, p < 0.001) and MACE (9.6 % versus 15.1 %, p < 0.001) as compared to control group. Their eGFR also significantly improved (0.4 +/- 9.3 versus-5.5 +/- 10.6 ml/min/1.73 m2, p < 0.001). These patients also had a greater reduction in HbA1c (-0.40 +/- 1.13 versus-0.04 +/- 1.47 %, p < 0.001), and insulin requirement (-8.8 +/- 35.2 versus 4.1 +/- 19.4 units/day, p < 0.001). After adjusting for confounders, SGLT2 in-hibitors protected against kidney-related adverse events (odds ratio [OR] 0.48, 95 % confidence interval [CI] 0.33 - 0.71, p < 0.001) and MACE (OR 0.47, 95 % CI 0.37 - 0.60, p < 0.001). Apart from a marginally higher rate of fungal urinary tract infection (0.08 +/- 0.66 versus 0.03 +/- 0.23 episodes per year, p < 0.001), SGLT2 inhibitor use was not associated with other side effects. Conclusions: SGLT2 inhibitor improved kidney function, glycemic profile, and reduced adverse kidney-related and cardiovascular events in diabetic patients with advanced CKD.