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

  • E. G. Dorsey-Treviño
  • J. G. González-González
  • N. Alvarez-Villalobos
  • V. González-Nava
  • B. M. Contreras-Garza
  • A. Díaz González-Colmenero
  • G. Rodríguez-Tamez
  • F. J. Barrera-Flores
  • A. M. Farrell
  • V. M. Montori
  • R. Rodriguez-GutierrezEmail author
Original Article



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.


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).


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.


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.


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



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.

Author contributions

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.


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

Compliance with ethical standards

Conflict of interest

All authors declare having no conflicts of interests or financial disclosures.

Research involving human participants and/or animals

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

The study does not require an informed consent as no participants were recruited.

Supplementary material

40618_2019_1103_MOESM1_ESM.docx (1.7 mb)
Supplementary material 1 (DOCX 1700 kb)


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Copyright information

© Italian Society of Endocrinology (SIE) 2019

Authors and Affiliations

  • E. G. Dorsey-Treviño
    • 1
    • 2
  • J. G. González-González
    • 1
    • 2
    • 3
  • N. Alvarez-Villalobos
    • 2
    • 3
    • 4
  • V. González-Nava
    • 2
  • B. M. Contreras-Garza
    • 2
  • A. Díaz González-Colmenero
    • 1
    • 2
  • G. Rodríguez-Tamez
    • 2
  • F. J. Barrera-Flores
    • 1
    • 2
  • A. M. Farrell
    • 5
  • V. M. Montori
    • 4
    • 6
  • R. Rodriguez-Gutierrez
    • 1
    • 2
    • 4
    • 6
    Email author
  1. 1.Endocrinology Division, Department of Internal Medicine, University Hospital “Dr. José E. González”Universidad Autonoma de Nuevo LeonMonterreyMexico
  2. 2.Plataforma INVEST Medicina UANL—KER Unit Mayo Clinic (KER Unit México)Universidad Autonoma de Nuevo LeonMonterreyMexico
  3. 3.Research Unit, University Hospital “Dr. José E. González”Universidad Autonoma de Nuevo LeonMonterreyMexico
  4. 4.Knowledge and Evaluation Research Unit in EndocrinologyMayo ClinicRochesterUSA
  5. 5.Mayo Medical LibraryMayo ClinicRochesterUSA
  6. 6.Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of MedicineMayo ClinicRochesterUSA

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