The association between sodium/glucose cotransporter-2 inhibitors and adverse clinical events in patients with chronic kidney disease: a systematic review and meta-analysis of randomised controlled trials

Abstract

Background

The purpose of this systematic review and meta-analysis was to evaluate the common clinical adverse events associated with sodium/glucose cotransporter-2 inhibitor (SGLT2i) use compared to placebo in patients with chronic kidney disease (CKD) with or without type 2 diabetes.

Methods

Twelve articles were chosen via a systematic search of the PubMed, Embase, and Cochrane Library databases. We screened for randomised placebo-controlled trials. The main clinical adverse events included diabetes ketoacidosis (DKA), amputation, and volume depletion. We performed heterogeneity testing and assessment of publication bias.

Results

In all, 65 600 patients were included in the analysis. Compared to placebo, SGLT2i may increase the risk of DKA and volume depletion in patients with CKD with or without type 2 diabetes. For DKA, compared with placebo, the combined effect of SGLT2i was OR 2.03 (95% CI: 1.28 to 3.23 I²: 2.3%, P: 0.420). For volume depletion, compared with placebo, the combined effect of SGLT2i was OR 1.24 (95% CI: 1.13 to 1.37 I²: 0.0%, P: 0.484). For the risk of amputation, despite low heterogeneity for amputation, the forest plot indicated no statistical significance, and thus it cannot be concluded that SGLT2i increases the risk of amputation. Compared with placebo, the combined effect of SGLT2i was OR 1.10 (95% CI: 0.94 to 1.29 I²: 0.0%, P: 0.642).

Conclusion

The use of SGLT2i may increase the risk of DKA and volume depletion in patients with chronic renal insufficiency with or without type 2 diabetes.

Keywords:

• SGLT2i
• chronic kidney disease
• diabetes ketoacidosis
• volume depletion

Acknowledgements

The authors would like to thank all the reviewers who participated in the review and MJ Editor (www.mjeditor.com) for its linguistic assistance during the preparation of this manuscript.

Patient and public involvement

Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Patient consent for publication

Not applicable.

Authors’ contributors

The FFW, TTY, and CL systems in our team searched all clinical randomised controlled trials (RCTs) involving SGLT2i in the PubMed, Embase and Cochrane Library databases in a standardised way. And TTY collected basic information of all patients who met the requirements. FRW provided ideas for the article and finally checked the article. YZ completed all the pictures and wrote the whole article and checked all the data.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (Grant Number 81874415).