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Safety of sodium-glucose co-transporter-2 inhibitors on amputation across categories of baseline cardiovascular disease and diuretics use in patients with type 2 diabetes

Park, Sohee; Jeong, Han Eol; Bea, Sungho; Yu, Oriana; Cho, Young Min; You, Seng Chan; Man, Kenneth KC; (2023) Safety of sodium-glucose co-transporter-2 inhibitors on amputation across categories of baseline cardiovascular disease and diuretics use in patients with type 2 diabetes. Diabetes, Obesity and Metabolism , 25 (11) pp. 3248-3258. 10.1111/dom.15221. Green open access

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Abstract

Aim: To assess the risk of amputation associated with sodium-glucose co-transporter-2 inhibitors (SGLT2is) among patients with type 2 diabetes, across categories of baseline cardiovascular disease (CVD) and diuretic use (DU). / Materials and Methods: We conducted an active comparator, new-user cohort study using Korea's nationwide claims data (2015-2020). The study cohort consisted of patients with type 2 diabetes who initiated SGLT2is or dipeptidyl peptidase-4 inhibitors (DPP4is). Cohort entry was defined by first prescription date. We then classified patients into four discrete subcohorts based on their baseline status of CVD and DU as (1) CVD+/DU+, (2) CVD+/DU-, (3) CVD-/DU+ and (4) CVD-/DU-. We performed 1:1 propensity score (PS) matching within each cohort and estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of amputation with SGLT2is versus DPP4is using Cox models. / Results: We identified 219 900 PS-matched pairs of SGLT2is and DPP4is (CVD+/DU+, n = 11 719; CVD+/DU-, n = 26 092; CVD-/DU+, n = 26 894; and CVD-/DU-, n = 155 195), with well-balanced baseline covariates across all cohorts. Significantly lower risks of amputation with SGLT2is versus DPP4is were found in CVD+/DU+ (HR 0.36, 95% CI 0.14-0.90), CVD+/DU- (0.45, 0.21-0.99) and CVD-/DU- (0.48, 0.33-0.70), but not in CVD-/DU+ (0.54, 0.26-1.12). Consistent trends in estimates were found across various sensitivity analyses. / Conclusions: Initiating SGLT2is against DPP4is did not increase the risk of amputation across patient populations of varying vulnerability. These findings based on routine practice will reassure clinicians of the safety of SGLT2is with regard to amputation risk in selected high-risk patients with type 2 diabetes.

Type: Article
Title: Safety of sodium-glucose co-transporter-2 inhibitors on amputation across categories of baseline cardiovascular disease and diuretics use in patients with type 2 diabetes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/dom.15221
Publisher version: https://doi.org/10.1111/dom.15221
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: amputation, cardiovascular disease, diuretics, SGLT2 inhibitors, type 2 diabetes
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Practice and Policy
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10173317
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