Risks of diabetic foot syndrome and amputation associated with sodium glucose co-transporter 2 inhibitors: A Meta-analysis of Randomized Controlled Trials.

Abstract

BACKGROUND:

The U.S. Food and Drug Administration recently issued a safety communication requiring new warnings of increased leg and foot amputation risk be added to canagliflozin drug labelling. However, the risk associated with other sodium-glucose co-transporter 2 inhibitors (SGLT2i) remains uncertain.

AIM:

This meta-analysis aimed to evaluate the potential risks of diabetic foot syndrome (DFS) and amputation associated with SGLT2i.

METHODS:

Relevant databases were searched from inception to June 14, 2017 to identify randomized controlled trials (RCTs) that evaluated risks of DFS and amputation associated with SGLT2i use. A random effects model was performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs) using STATA 14.

RESULTS:

Fourteen RCTs involving 26,167 patients were eligible for this meta-analysis. SGLT2i were not significantly associated with increased risk of DFS compared with placebo (OR 1.05, 95% CI: 0.58-1.89). No significant association was observed in the subgroup and sensitivity analysis on DFS risk either. Although SGLT2i, as a class, were not significantly associated with amputation risk (OR 1.40, 95% CI: 0.81-2.41), subgroup analysis showed an increased incidence of amputation in participants using canagliflozin (OR 1.89, 95% CI: 1.37-2.60), compared with oral anti-diabetic drugs and placebo, but not in those using empagliflozin (OR 1.02, 95% CI: 0.71-1.48).

CONCLUSION:

Current evidence from RCTs suggests that canagliflozin may be positively associated with an increased risk of amputation. Due to limited data, large-scale studies are required to further clarify the association between amputation and individual SGLT2i drugs.

• Authors: D Li, J Yufeng Yang, T Wang, S Shen, H Tang
• Journal: Diabetes & metabolism (Diabetes Metab) Vol. 44 Issue 5 Pg. 410-414 (11 2018) ISSN: 1878-1780 [Electronic] France
• PMID: 29506779 (Publication Type: Journal Article, Meta-Analysis)
• Copyright: Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical References

• Hypoglycemic Agents
• Sodium-Glucose Transporter 2 Inhibitors

Topics

• Amputation, Surgical
• Diabetes Mellitus, Type 2 (drug therapy)
• Diabetic Foot (chemically induced, epidemiology)
• Humans
• Hypoglycemic Agents (adverse effects, therapeutic use)
• Incidence
• Randomized Controlled Trials as Topic
• Risk
• Sodium-Glucose Transporter 2 Inhibitors (adverse effects, therapeutic use)