Physicians' Academy for Cardiovascular Education

Pooled analysis shows no new safety concerns of SGLT2i in T2DM patients with CKD

Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials

Literature - Tuttle KR, Levin A, Nangaku M, et al. - Diabetes Care. 2022 Apr 26;dc212034. doi: 10.2337/dc21-2034

Introduction and methods


Several clinical guidelines recommend the use of an SGLT2i in patients with T2DM and CKD [1,2]. However , recommendation for eGFR levels at which SGLT2i can be initiated or should be discontinued vary between agents, and labeling for agents may vary between countries and regions. Knowing that approximately 40% of T2DM patients will eventually develop CKD [3,4], it is interesting that the SGLT2i empagliflozin has been shown to reduce the onset and progression of CKD in T2DM [5]. But what are the safety risks of empagliflozin use if T2DM patients already have CKD?

Aim of the study

The study aim was to assess the safety of empagliflozin in T2DM patients with moderate to severe CKD (category G3-4) who were enrolled in earlier RCTs on the effect of empagliflozin versus placebo.


The authors pooled data from 19 randomized, placebo-controlled, phase 1–4 clinical trials and 1 randomized, placebo-controlled extension study in which T2DM patients received 10 or 25 mg empagliflozin or placebo daily. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (2009).


The outcome was the time to the first occurrence of investigator-reported adverse events (AEs).

Main results

T2DM patients with CKD

Adverse events


In a comprehensive safety analysis, treatment with empagliflozin did not result in an overall increased risk of serious AEs, AEs leading to discontinuation, or events of special interest compared with placebo in T2DM patients with moderate to severe CKD, irrespective of baseline eGFR. In addition, empagliflozin may have beneficial effects on the development of hyperkalemia and edema in these patients.


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