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Sodium-glucose cotransporter 2 (SGLT-2) inhibitors and microvascular outcomes in patients with type 2 diabetes: systematic review and meta-analysis

Abstract

Purpose

The effect of the sodium-glucose 2 (SGLT-2) inhibitors on microvascular complications remains uncertain. We performed a systematic review to determine the efficacy of the SGLT-2 inhibitors on microvascular outcomes in patients with type 2 diabetes.

Methods

A comprehensive search was performed using Ovid, MEDLINE, EMBASE, Web of Science, and Scopus from inception to May 2019. Randomized trials comparing SGLT-2 inhibitors with placebo or other medication for type 2 diabetes for ≥ 4 weeks were included. Diabetes-related microvascular complications such as nephropathy, retinopathy, neuropathy, and peripheral vascular disease were evaluated. A random-effect model using mean differences for continuous outcomes and risk ratio for dichotomous outcomes was used to synthesize data. PROSPERO (CRD 42017076460).

Results

A total of 40 RCTs with overall moderate quality of evidence were included. SGLT-2 inhibitors reduced the risk of renal-replacement therapy (0.65; 95% CI 0.54–0.79), renal death (0.57; 95% CI 0.49–0.65), and progression of albuminuria (0.69; 95% CI 0.66–0.73). Conversely, they appeared ineffective in maintaining eGFR (0.33; 95% CI − 0.74 to 1.41) or reducing serum creatinine (− 0.07; 95% CI − 0.26 to 0.11), whereas urine albumin–creatinine ratio (− 23.4; 95% CI − 44.6 to − 2.2) was reduced. Risk of amputation was non-significant (1.30; 95% CI 0.93–1.83). No available data were found regarding neuropathy and retinopathy to perform a quantitative analysis.

Conclusion

SGLT-2 inhibitors may reduce the risk of renal patient-important outcomes but fail to improve surrogate outcomes. Apparently, no increased risk of amputations was observed with these medications. No data were available regarding other microvascular complications.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank the Research Unit from the School of Medicine of the Universidad Autonoma de Nuevo Leon, Monterrey, Mexico and the Knowledge and Evaluation Research (KER) Unit from the Mayo Clinic, Rochester, MN for their support and guidance in the conduct of this systematic review.

Funding

No grant, funding source, or any other kind of financial support was received for the elaboration of this study.

Author information

EGD-T, ADG-C, and RR-G conceived the idea of the study. NA-V and AMF performed the search strategy. EGD-T, BMC-G, FJB-F, VG-N, ADG-C, and GR-T screened potentially eligible articles. EGD-T, BMC-G, and VG-N extracted the data and rated the quality of the evidence. EGDT and NA-V analyzed the data. EGD-T wrote the first manuscript with input of RR-G. RR-G, VMM, and JGG-G critically reviewed, revised, and provided significant contribution to the manuscript. All authors agreed on the final version of the manuscript.

Correspondence to R. Rodriguez-Gutierrez.

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Dorsey-Treviño, E.G., González-González, J.G., Alvarez-Villalobos, N. et al. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors and microvascular outcomes in patients with type 2 diabetes: systematic review and meta-analysis. J Endocrinol Invest 43, 289–304 (2020). https://doi.org/10.1007/s40618-019-01103-9

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Keywords

  • Sodium-glucose cotransporter 2 inhibitors
  • Microvascular complications
  • Type 2 diabetes mellitus
  • Systematic review
  • Meta-analysis