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Lower limb amputations: protection with GLP-1 receptor agonists rather than increased risk with SGLT2 inhibitors?

SCHEEN, André

2022 • In Diabetes and Metabolism, 48 (2), p. 101325

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https://hdl.handle.net/2268/289517

DOI
10.1016/j.diabet.2022.101325

PubMed
35121148

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Keywords :

Amputation; GLP-1 receptor agonist; Meta-analysis; Real-life; SGLT2 inhibitor; Safety; Internal Medicine; Endocrinology, Diabetes and Metabolism; Endocrinology; General Medicine

Abstract :

[en] An increased risk of lower limb amputations (LLA) has been suspected with the use of sodium-glucose cotransporter type 2 inhibitors (SGLT2is) after the publication of CANVAS with canagliflozin compared with placebo. A more than twofold increase of the risk of LLA in SGLT2i users compared with patients treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs) has been reported in a Scandinavian cohort observational study, yet other observational studies gave less alarming findings. Our meta-analysis of 12 retrospective cohorts revealed significant increase in LLA with a HR 1.15 (95% CI 1.05-1.24, I² 69%) when comparing SGLT2i users versus GLP-1RA users. However, another meta-analysis of observational studies showed no increased risk when SGLT2is were compared to dipeptidyl peptidase-4 inhibitors (DPP-4is) and some data showed a lower incidence of LLA in patients treated with GLP-1RAs compared to those treated with DPP-4is. When summarizing all available data with direct and indirect comparisons, a conclusion emerges that SGLT2is do not increase the risk of LLA but rather that GLP-1RAs may reduce such a risk.

Disciplines :

Endocrinology, metabolism & nutrition
Pharmacy, pharmacology & toxicology

Author, co-author :

SCHEEN, André ; Centre Hospitalier Universitaire de Liège - CHU > > Service de diabétologie, nutrition, maladies métaboliques

Language :

English

Title :

Lower limb amputations: protection with GLP-1 receptor agonists rather than increased risk with SGLT2 inhibitors?

Publication date :

March 2022

Journal title :

Diabetes and Metabolism

ISSN :

1262-3636

eISSN :

1878-1780

Publisher :

Elsevier Masson s.r.l., France

Volume :

48

Issue :

2

Pages :

101325

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://api.elsevier.com/content/article/PII:S1262363622000088?httpAccept=text/xml

Funding text :

The author thanks Monique Marchand (M.M.) for her valuable help in the literature search and the subsequent statistical analyses

Available on ORBi :

since 08 April 2022

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