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Cited by 63Diabetes Treatment and ManagementDiabetic Foot Ulcer Assessment and ManagementDiabetes Management and Research

Risk of amputation with canagliflozin across categories of age and cardiovascular risk in three US nationwide databases: cohort study

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Fralick, Michael, Kim, Seoyoung C, Schneeweiss, Sebastian, Everett, Brendan M, Glynn, Robert J, Patorno, Elisabetta·2020·BMJ
DOI 10.1136/bmj.m2812PMC PMC7445737
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Abstract

Objective: To estimate the rate of lower limb amputation among adults newly prescribed canagliflozin according to age and cardiovascular disease. Design: Population based, new user, cohort study. Data sources: Two commercial and Medicare claims databases, 2013-17. Participants: Patients newly prescribed canagliflozin were propensity score matched 1:1 with patients newly prescribed a glucagon-like peptide-1 (GLP-1) receptor agonist. Hazard ratios and rate differences per 1000 person years were computed for the rate of lower limb amputation in the following four groups: group 1, patients aged less than 65 years without baseline cardiovascular disease; group 2, patients aged less than 65 with baseline cardiovascular disease; group 3, patients aged 65 or older without baseline cardiovascular disease; group 4, patients aged 65 or older with baseline cardiovascular disease. Within each group, pooled hazard ratio and rate difference per 1000 person years were calculated by meta-analysis. Intervention: Canagliflozin versus a GLP-1 agonist. Main outcome measures: Lower limb amputation requiring surgery. Results: Across the three databases, 310 840 propensity score matched adults who started canagliflozin or a GLP-1 agonist were identified. The hazard ratio and rate difference per 1000 person years for amputation in adults receiving canagliflozin compared with a GLP-1 agonist for each group was: group 1, hazard ratio 1.09 (95% confidence interval 0.83 to 1.43), rate difference 0.12 (−0.31 to 0.55); group 2, hazard ratio 1.18 (0.86 to 1.62), rate difference 1.06 (−1.77 to 3.89); group 3, hazard ratio 1.30 (0.52 to 3.26), rate difference 0.47 (−0.73 to 1.67); and group 4, hazard ratio 1.73 (1.30 to 2.29), rate difference 3.66 (1.74 to 5.59). Conclusions: The increase in rate of amputation with canagliflozin was small and most apparent on an absolute scale for adults aged 65 or older with baseline cardiovascular disease, resulting in a number needed to treat for an additional harmful outcome of 556 patients at six months (that is, 18 more amputations per 10 000 people who received canagliflozin). These results help to contextualize the risk of amputation with canagliflozin in routine care.

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Authors
Fralick, M., Kim, S. C., Schneeweiss, S., Everett, B. M., Glynn, R. J., & Patorno, E.
Affiliations
Brigham and Women's Hospital (US)
Corresponding author
Fralick, Michael
ORCID
Venue
BMJ
Publisher
BMJ
Published
2020-08-25
Volume
370
Pages
m2812
ISSN
1756-1833 (ISSN-L)
DOI
10.1136/bmj.m2812
PMC
PMC7445737
OpenAlex
W3080635855
Cited by
63
References
45
Citations by year
2026: 3 · 2025: 8 · 2024: 6 · 2023: 16 · 2022: 11 · 2021: 15 · 2020: 4
FWCI
8.67
Type
journal article
Language
en
Open access
Licence
Locations
  • BMJ (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
National Institute on Aging (K08AG055670)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetic Foot Ulcer Assessment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
canagliflozin, lower limb amputation, cardiovascular risk, age, GLP-1 receptor agonists, SGLT2 inhibitors, adverse drug reactions, type 2 diabetes
MeSH terms
Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Aged, Amputation, Surgical, Cardiovascular Diseases, Cardiovascular System, Diabetes Mellitus, Type 2, Female, Humans, Longitudinal Studies, Male, Middle Aged, Risk Factors, United States, Case-Control Studies, Databases, Factual, Age Distribution, Glucagon-Like Peptide 1, Propensity Score

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