SGLT2 inhibitors improved outcomes in stage five chronic kidney disease
1. In this retrospective cohort study, among patients with type 2 diabetes (T2D) and stage five chronic kidney disease (CKD), the use of a sodium-glucose cotransporter-2 inhibitor (SGLT2i) was associated with a lower risk of dialysis, cardiovascular events, diabetic ketoacidosis (DKA), and acute kidney injury (AKI).
2. SGLT2i use was not associated with a difference in all-cause mortality.
Evidence Rating Level: 2 (Good)
Study Rundown: The incidence and prevalence of CKD have increased steadily worldwide, resulting in significant morbidity and mortality. Mainstay therapy includes antihypertensive and antidiabetic medications to reduce the risk of dialysis. SGLT2i has emerged as a novel class of medications to improve long-term renal outcomes in CKD with or without T2D. However, evidence of its use is lacking in patients with an estimated glomerular filtration rate (eGFR) less than 20mL/min/1.73m2. This retrospective cohort study, designed as a target trial emulation, assessed the impact of SGLT2i use on outcomes of patients with stage five CKD and T2D in Taiwan. Between 2016 and 2021, SGLT2i use was associated with a lower risk of dialysis, adverse cardiovascular events, DKA, and AKI. Initiation of an SGLT2i in stage five CKD was also associated with lower dialysis risk. However, all-cause mortality rates were similar between SGLT2i users and non-users. The study was limited by the lack of lifestyle information from the database and follow-up assessment of renal function. Nevertheless, it provided initial evidence demonstrating the benefits of using and initiating SGLT2is in patients with advanced CKD and concurrent T2D.
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In-Depth [randomized controlled trial]: This study was a sequential target-emulated trial utilizing retrospective health information from Taiwan’s National Health Insurance Research Database to assess the impact of SGLT2i use among patients with stage 5 CKD and T2D. The study included patients under 100 years of age who had T2D and stage 5 CKD (defined as eGFR less than 15mL/min/1.73m2) between May 2016, when SGLT2i was covered by insurance in Taiwan, and October 2021. Exclusion criteria included dialysis history, lack of oral antidiabetic medication use during the study period, and missing key demographic information. The study was carried out in sequential emulated weekly trials, cumulatively including 23,854 SGLT2i users and 23,892 non-users. The primary outcomes were the incidence of dialysis, hospitalization for heart failure, acute myocardial infarction, and all-cause mortality during the study period. Overall, in intention-to-treat model, compared to no SGLT2i use, SGLT2i use was associated with lower incidence rates of long-term dialysis (1.69/1000 person-years [PYs] vs. 4.76/1000 PYs) (adjusted hazard ratio [AHR] 0.34, 95% confidence interval [CI] 0.27-0.43), hospitalization for heart failure (21.07/1000 PYs vs. 21.14/1000 PYs) (AHR 0.80, 95% CI 0.73-0.86), and acute myocardial infarction (4.02/1000 PYs vs. 5.16/1000 PYs) (AHR 0.61, 95% CI 0.52-0.73). Notably, SGLT2i was also associated with lower incidence rates of DKA (AHR 0.78, 95% CI 0.71-0.85) and AKI (AHR 0.80, 95% CI 0.70-0.90), despite some previous evidence that SGLT2i may increase the risk for these complications. Kaplan-Meier analysis also demonstrated a lower cumulative incidence of long-term dialysis with SGLT2i use. SGLT2i use, however, was not associated with any difference in all-cause mortality compared to no SGLT2i use (AHR 1.11, 95% CI 0.99-1.24). In summary, these results provided the first initial evidence for the benefits of SGLT2is in patients with stage 5 CKD and concurrent T2D, prompting clinical trials to further substantiate these findings.
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