Lower-limb amputations in patients treated with SGLT2 inhibitors versus DPP-4 inhibitors: A meta-analysis of observational studies

Scheen, André

doi:10.1016/j.deman.2022.100054

Article (Scientific journals)

Lower-limb amputations in patients treated with SGLT2 inhibitors versus DPP-4 inhibitors: A meta-analysis of observational studies

Scheen, André

2022 • In Diabetes Epidemiology and Management, 6, p. 100054

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/312598

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10.1016/j.deman.2022.100054

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Keywords :

Amputation; Gliflozin; Meta-analysis; Real-life; Safety; SGLT2 inhibitor

Abstract :

[en] Background: An increased risk of lower limb amputations (LLA) has been suspected with the use of sodiumglucose cotransporter type 2 inhibitors (SGLT2is) in the CANVAS programme with canagliflozin and in pharmacovigilance reports with all SGLT2is. Even if reassuring observations were reported in several large prospective placebo-controlled cardiovascular outcome trials, real-life conditions in more frailty patients might be associated with a higher risk. Methods: This work analyses the incidence of LLA events in retrospective observational studies that compared SGLT2i users with patients treated with dipeptidyl peptidase-4 inhibitors (DPP-4is), a pharmacological class with an excellent safety profile. A meta-analysis of 12 comparative cohort studies (9 of them using a propensity score matching) worldwide has been performed. Results: The relative risk of LLA tended to be slightly lower in SGLT2i users (1228 LLA events/711159 patients) versus DPP-4i users: 2167 LLA events/1121914 patients, with a hazard ratio 0.91, 95% CI 0.85-0.98, p=0.01). However, a high between-study heterogeneity was observed (I2 = 79%, P<0.00001), which could not be explained by differences across countries, between studies with/without propensity score matching, between cohorts treated with/without canagliflozin or between patients with/without peripheral artery disease. The incidence rate expressed as a number of LLA events per 1000 patient.years was almost similar among SGLT2i users and DPP-4i users (2.48§1.45 versus 2.67§3.09, p=0.849). Conclusion: Physicians should not fear an increased risk of LLA with SGLT2is compared with DPP-4is in daily clinical practice, even if caution may be advised in some patients exposed to special conditions.

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 in patients treated with SGLT2 inhibitors versus DPP-4 inhibitors: A meta-analysis of observational studies

Publication date :

2022

Journal title :

Diabetes Epidemiology and Management

eISSN :

2666-9706

Volume :

Pages :

100054

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://www.sciencedirect.com/science/article/pii/S2666970622000051

Available on ORBi :

since 01 February 2024

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