Christie Rampersad1, Eyal Kraut2, Reid H Whitlock3, Paul Komenda4, Vincent Woo2, Claudio Rigatto4, Navdeep Tangri4. 1. University of Manitoba, Rady Faculty of Health Sciences, Max Rady College of Medicine, Department of Internal Medicine. Electronic address: umrampec@myumanitoba.ca. 2. University of Manitoba, Rady Faculty of Health Sciences, Max Rady College of Medicine, Department of Endocrinology. 3. Seven Oaks Hospital, Chronic Disease Innovation Centre. 4. University of Manitoba, Rady Faculty of Health Sciences, Max Rady College of Medicine, Department of Internal Medicine; Seven Oaks Hospital, Chronic Disease Innovation Centre.
Abstract
RATIONALE & OBJECTIVE: Sodium glucose cotransporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease and prevent heart failure events. However, SGLT2 inhibitors may increase the risk of acute kidney injury (AKI). Our objective was to assess whether SGLT2 inhibitor use, compared to all other glucose lowering drugs (oGLD), is associated with increased rates of AKI. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults in Manitoba, Canada with type 2 diabetes mellitus (T2DM) followed from June 2014 until March 2017. EXPOSURES: Initial SGLT2 inhibitor or oGLD use ascertained through a province-wide outpatient prescription database. OUTCOME: The primary outcome was incident AKI, identified either by a rise in serum creatinine and/or hospital discharge codes for AKI while taking glucose lowering drugs (on-treatment approach). ANALYTICAL APPROACH: A propensity score analysis was used to assemble groups of incident users of SGLT2 inhibitors and a 1:1 matched set of users of oGLD. The rate of AKI was compared across matched groups using cause-specific hazards models. Sensitivity analyses considered exposure to be constant throughout follow-up after initiation of the drug (intention-to-treat approach) or incorporated recurrent exposures (new user design). RESULTS: Comparing 4,778 incident users of SGLT2 inhibitor to 4,778 incident users of oGLD, there were no differences observed in the primary outcome: (HR 0.64, 95% CI 0.40 - 1.03, p = 0.064) using an on-treatment approach. In neither set of sensitivity analyses were SGLT2 inhibitors associated with an increased risk of AKI. LIMITATIONS: Drug choice may have been related to AKI risk, laboratory data were obtained from clinical care, and changes in adverse event reporting may have followed the FDA warning. There were insufficient data to compare individual SGLT2 inhibitors. CONCLUSIONS: Compared to oGLD, SGLT2 inhibitors were not observed to be associated with an increased risk of AKI in a clinical population-based cohort.
RATIONALE & OBJECTIVE:Sodium glucose cotransporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease and prevent heart failure events. However, SGLT2 inhibitors may increase the risk of acute kidney injury (AKI). Our objective was to assess whether SGLT2 inhibitor use, compared to all other glucose lowering drugs (oGLD), is associated with increased rates of AKI. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults in Manitoba, Canada with type 2 diabetes mellitus (T2DM) followed from June 2014 until March 2017. EXPOSURES: Initial SGLT2 inhibitor or oGLD use ascertained through a province-wide outpatient prescription database. OUTCOME: The primary outcome was incident AKI, identified either by a rise in serum creatinine and/or hospital discharge codes for AKI while taking glucose lowering drugs (on-treatment approach). ANALYTICAL APPROACH: A propensity score analysis was used to assemble groups of incident users of SGLT2 inhibitors and a 1:1 matched set of users of oGLD. The rate of AKI was compared across matched groups using cause-specific hazards models. Sensitivity analyses considered exposure to be constant throughout follow-up after initiation of the drug (intention-to-treat approach) or incorporated recurrent exposures (new user design). RESULTS: Comparing 4,778 incident users of SGLT2 inhibitor to 4,778 incident users of oGLD, there were no differences observed in the primary outcome: (HR 0.64, 95% CI 0.40 - 1.03, p = 0.064) using an on-treatment approach. In neither set of sensitivity analyses were SGLT2 inhibitors associated with an increased risk of AKI. LIMITATIONS: Drug choice may have been related to AKI risk, laboratory data were obtained from clinical care, and changes in adverse event reporting may have followed the FDA warning. There were insufficient data to compare individual SGLT2 inhibitors. CONCLUSIONS: Compared to oGLD, SGLT2 inhibitors were not observed to be associated with an increased risk of AKI in a clinical population-based cohort.
Authors: Min Zhuo; Julie M Paik; Deborah J Wexler; Joseph V Bonventre; Seoyoung C Kim; Elisabetta Patorno Journal: Am J Kidney Dis Date: 2021-11-08 Impact factor: 11.072
Authors: Wajd Alkabbani; Arsene Zongo; Jasjeet K Minhas-Sandhu; Dean T Eurich; Baiju R Shah; Mhd Wasem Alsabbagh; John-Michael Gamble Journal: BMJ Open Diabetes Res Care Date: 2021-12