Diabetes, obesity & metabolismSep 13, 2017

Risk of leg amputations in people with type 2 diabetes treated with SGLT2 inhibitors in the USA

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Apr 5, 2026

Abstract

The incidence rate of below-knee lower extremity amputation was 1.18 events per 1000 person-years for new users of canagliflozin.

Among 118,018 new users of SGLT2 inhibitors, including 73,024 on canagliflozin, the incidence rates of BKLE amputation were 1.22 for SGLT2 inhibitors, 1.26 for canagliflozin, and 1.87 for non-SGLT2 inhibitor antihyperglycaemic agents.
In a matched comparison of 63,845 users each of canagliflozin and non-SGLT2 inhibitor AHAs, the incidence rates of BKLE amputation were 1.18 and 1.12 events per 1000 person-years, respectively.
The hazard ratio for BKLE amputation between canagliflozin and non-SGLT2 inhibitor AHAs was 0.98, indicating no significant difference in risk.
P values and calibrated P values showed no evidence of increased risk of BKLE amputation associated with canagliflozin use compared to non-SGLT2 inhibitor AHAs.

Simplified

AIMS: To examine the incidence of amputation in patients with type 2 diabetes mellitus (T2DM) treated with sodium glucose co-transporter 2 (SGLT2) inhibitors overall, and canagliflozin specifically, compared with non-SGLT2 inhibitor antihyperglycaemic agents (AHAs).

MATERIALS AND METHODS: Patients with T2DM newly exposed to SGLT2 inhibitors or non-SGLT2 inhibitor AHAs were identified using the Truven MarketScan database. The incidence of below-knee lower extremity (BKLE) amputation was calculated for patients treated with SGLT2 inhibitors, canagliflozin, or non-SGLT2 inhibitor AHAs. Patients newly exposed to canagliflozin and non-SGLT2 inhibitor AHAs were matched 1:1 on propensity scores, and a Cox proportional hazards model was used for comparative analysis. Negative controls (outcomes not believed to be associated with any AHA) were used to calibrate P values.

RESULTS: Between April 1, 2013 and October 31, 2016, 118 018 new users of SGLT2 inhibitors, including 73 024 of canagliflozin, and 226 623 new users of non-SGLT2 inhibitor AHAs were identified. The crude incidence rates of BKLE amputation were 1.22, 1.26 and 1.87 events per 1000 person-years with SGLT2 inhibitors, canagliflozin and non-SGLT2 inhibitor AHAs, respectively. For the comparative analysis, 63 845 new users of canagliflozin were matched with 63 845 new users of non-SGLT2 inhibitor AHAs, resulting in well-balanced baseline covariates. The incidence rates of BKLE amputation were 1.18 and 1.12 events per 1000 person-years with canagliflozin and non-SGLT2 inhibitor AHAs, respectively; the hazard ratio was 0.98 (95% confidence interval 0.68-1.41; P = .92, calibrated P = .95).

CONCLUSIONS: This real-world study observed no evidence of increased risk of BKLE amputation for new users of canagliflozin compared with non-SGLT2 inhibitor AHAs in a broad population of patients with T2DM.

Key numbers

1.22 per 1000 person-years

Crude Incidence Rate of BKLE Amputation (SGLT2 inhibitors)

Incidence rate for patients using SGLT2 inhibitors.

1.26 per 1000 person-years

Crude Incidence Rate of BKLE Amputation (Canagliflozin)

Incidence rate for patients using canagliflozin.

0.98

Hazard Ratio for BKLE Amputation (Canagliflozin vs. Non-SGLT2 AHAs)

Comparative analysis of amputation risk between canagliflozin and non-SGLT2 inhibitors.

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Competing interests

Z. Y., F. J. D., P. B. R., M. J. S., P. E. S., M. D. and N. R. are full‐time employees of Janssen Research & Development, LLC. J. A. B. is a full‐time employee of Johnson & Johnson, LLC.

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Risk of leg amputations in people with type 2 diabetes treated with SGLT2 inhibitors in the USA

Abstract

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