Risk of lower extremity amputations in patients with type 2 diabetes mellitus treated with sodium glucose co-transporter 2 inhibitors (SGLT2i) inhibitors in the United States: A retrospective cohort study

Diabetes, Obesity and Metabolism | September 13, 2017

Yuan Z, et al. - A retrospective cohort study was conducted to analyze the incidence of amputation in patients with type 2 diabetes mellitus (T2DM) treated with sodium glucose co-transporter 2 inhibitors (SGLT2i) overall, and canagliflozin specifically, compared with non-SGLT2i antihyperglycemic agents (AHAs). As per the outcomes, this real-world study found no evidence of increased risk of below-knee lower extremity amputation for new users of canagliflozin compared with non-sodium glucose co-transporter 2 inhibitors (SGLT2i) antihyperglycemic agents (AHAs) in a broad population of patients with type 2 diabetes mellitus.

Methods

  • Researchers distinguished patients with T2DM newly exposed to SGLT2i or non-SGLT2i AHAs applying the Truven MarketScan database.
  • They estimated incidence of below-knee lower extremity (BKLE) amputation for patients treated with SGLT2i, canagliflozin, or non-SGLT2i AHAs.
  • Thereafter, patients newly exposed to canagliflozin and non-SGLT2i AHAs were matched 1:1 on propensity scores, and a Cox proportional hazards model was used for comparative analysis.
  • They applied negative controls (outcomes not believed to be associated with any AHA) to calibrate P values.

Results

  • They distinguished 118,018 new users of SGLT2i, including 73,024 of canagliflozin, and 226,623 new users of non-SGLT2i AHAs between April 1, 2013-October 31, 2016.
  • It was noted that the crude incidence rate of BKLE amputation was 1.22, 1.26, and 1.87 events per 1,000 person-years with SGLT2i, canagliflozin, and non-SGLT2i AHAs, respectively.
  • For the comparative analysis, they demonstrated that 63,845 new users of canagliflozin were matched with 63,845 new users of non-SGLT2i AHAs, resulting in well-balanced baseline covariates.
  • The data indicated that the incidence rate of BKLE amputation was 1.18 and 1.12 events per 1,000 person-years with canagliflozin and non-SGLT2i AHAs, respectively; the hazard ratio (95% confidence interval) was 0.98 (0.68-1.41; P=0.92, calibrated P=0.95).

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