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OBJECTIVE: To assess the safety of empagliflozin in patients with type 2 diabetes and moderate to severe chronic kidney disease (CKD) (category G3-4) enrolled in clinical trials.
RESEARCH DESIGN AND METHODS: This analysis pooled data from 19 randomized, placebo-controlled, phase 1-4 clinical trials and 1 randomized, placebo-controlled extension study in which patients received empagliflozin 10 mg or 25 mg daily. Time to first occurrence of adverse events (AEs) was evaluated using Kaplan-Meier analysis and multivariable Cox regression models.
RESULTS: Among a total of 15,081 patients who received at least one study drug dose, 1,522, 722, and 123 were classified as having G3A, G3B, and G4 CKD, respectively, at baseline. Demographic and clinical characteristics were similar between treatment groups across CKD categories. Rates of serious AEs, AEs leading to discontinuation, and events of special interest (including lower limb amputations and acute renal failure [ARF]) were also similar between empagliflozin and placebo across CKD subgroups. In adjusted Cox regression analyses, risks for volume depletion and ARF were similar for empagliflozin and placebo in the combined group with CKD categories G3B and G4 and the G3A group. Notably lower risks were observed in both groups for hyperkalemia (hazard ratio 0.59 [95% CI 0.37-0.96, P = 0.0323] and 0.48 [0.26-0.91, P = 0.0243], respectively) and edema (0.47 [0.33-0.68, P < 0.0001] and 0.44 [0.28-0.68, P = 0.0002], respectively).
CONCLUSIONS: Use of empagliflozin in patients with type 2 diabetes and advanced CKD raised no new safety concerns and may have beneficial effects on the development of hyperkalemia and edema.
|Family Medicine (FM)/General Practice (GP)|
|General Internal Medicine-Primary Care(US)|
This analysis of > 15000 patients from empagliflozin randomized controlled trials included approximately 2400 patients with advanced chronic disease (eGFR: 45 to <60 mL/min/1.73 m2, G3B, 30 to <45 mL/min/1.73 m2 ; G4, 15 to <30 mL/min/1.73 m2) to due to diabetes. Despite FDA black box warnings, empagliflozin was not shown in this analysis to be associated with acute kidney injury or lower limb amputation.
The lower risk for hyperkalemia in the patients receiving an SGLT2 inhibitor may provide a potential additional benefit, but clinical relevance of this finding needs to be confirmed.
The compelling finding of a reduced risk for hyperkalemia may not be as commonly known as empagliflozin's (and presumably all SGLT2 inhibitors) benefits in CKD.