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Comment & Response
March 2019

Sodium-Glucose Cotransporter 2 Inhibitors and Amputations

Author Affiliations
  • 1Department of Pharmacy Practice, Presbyterian College School of Pharmacy, Clinton, South Carolina
JAMA Intern Med. 2019;179(3):451-452. doi:10.1001/jamainternmed.2018.8134

To the Editor In their recently published Original Investigation involving a population-based cohort trial, Chang and colleagues1 found a statistically significant increase in the risk of amputation among new users of sodium-glucose cotransporter 2 (SGLT-2) inhibitors when compared with use of oral antihyperglycemic agents. A risk of amputations and other vascular outcomes was not seen when use of SGLT-2 inhibitors was compared with use of dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 agonists. The mechanism of SGLT-2 inhibitors can only be speculated as glucosuria and volume depletion, which leads to a higher risk of peripheral artery disease and, ultimately, amputations. Based on the evidence, canagliflozin use has resulted in more reports of amputations compared with dapagliflozin and empagliflozin use. It should be noted that use of dapagliflozin and empagliflozin have been associated with toe amputations.2

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