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Association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and lower extremity amputation: A systematic

James Heyward1, Omar Mansour2, Lily Olson1

  • 1Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.

Plos One
|June 6, 2020
PubMed
Abstract

Insights

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) do not show a clear link to lower extremity amputations. While some studies suggest a potential increased risk, overall evidence remains inconsistent, warranting further investigation.

Area of Science:

  • Cardiology
  • Endocrinology
  • Pharmacology

Background:

  • The association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and lower extremity amputation risk is not well-established.
  • Type 2 diabetes mellitus (T2DM) patients are at increased risk for lower extremity complications.

Purpose of the Study:

  • To systematically review randomized controlled trials (RCTs) and observational studies.
  • To quantify the risk of lower extremity amputations associated with SGLT2i use in T2DM patients.

Main Methods:

  • Searched major databases (PubMed, EMBASE, Scopus, Cochrane) from January 2011 to February 2020.
  • Included RCTs and observational studies reporting lower extremity amputation outcomes.
  • Performed random and fixed effects meta-analyses for RCTs, assessed risk of bias.

Main Results:

  • Included 12 RCTs and 18 observational studies.
  • Random-effects meta-analysis of 7 RCTs showed no statistically significant association (RR 1.28, 95% CI 0.93-1.76), despite heterogeneity.
  • Fixed-effects analysis indicated an increased risk (RR 1.27, 95% CI 1.09-1.48). Subgroup analysis for canagliflozin showed a significant increase, while others did not. Observational data was too heterogeneous to pool.

Conclusions:

  • No consistent evidence links SGLT2i use to increased amputation risk.
  • The potential increased risk observed in the CANVAS trial for canagliflozin and some observational studies requires further research.

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