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Comparison of the risk of SGLT2is and NonSGLT2is in leading to amputation: A network meta-analysis

Mei Qiu1, Liang-Liang Ding2, Miao Zhang3

  • 1Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen 518110, China.

Journal of Diabetes and Its Complications
|December 9, 2020
PubMed
Abstract

Insights

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) show increased amputation risk compared to other diabetes drugs, particularly glucagon-like peptide 1 receptor agonists. However, SGLT2is do not significantly increase amputation risk when compared to placebo.

Area of Science:

  • Cardiovascular Medicine
  • Endocrinology
  • Pharmacology

Background:

  • The risk of amputation associated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) is a subject of ongoing debate.
  • Understanding comparative risks is crucial for patient safety and treatment guidelines.

Purpose of the Study:

  • To evaluate the relative risk of amputation among different SGLT2is and non-SGLT2i antihyperglycemic drugs (NonSGLT2is).
  • To conduct a network meta-analysis of large-scale studies to clarify these risks.

Main Methods:

  • A systematic search of Embase and PubMed databases was performed for large sample studies.
  • Bayesian network meta-analysis using a random-effects model was employed.
  • Hazard ratios (HR) and 95% confidence intervals (CI) were calculated to present effect sizes.

Main Results:

  • Seventeen studies involving over 4 million patients were analyzed.
  • SGLT2is significantly increased amputation risk compared to NonSGLT2is (HR: 1.38, 95% CI: 1.02-1.91).
  • Canagliflozin and overall SGLT2is showed increased risk versus glucagon-like peptide 1 receptor agonists (GLP1RAs), but empagliflozin and dapagliflozin did not show significant increases.

Conclusions:

  • While SGLT2is do not significantly elevate amputation risk against placebo, they do increase it when compared to NonSGLT2is, especially GLP1RAs.
  • Canagliflozin, in particular, demonstrated a significant increase in amputation risk compared to GLP1RAs.
Keywords:
AmputationCanagliflozinGLP1RAsNetwork meta-analysisSGLT2is

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