Sodium‐glucose cotransporter 2 inhibitors and the risk of venous thromboembolism: A population‐based cohort study

Author:

Aloe Stephanie12,Filliter Christopher2,Salmasi Shahrzad23,Igweokpala Samuel23,Yu Oriana H. Y.234,Tagalakis Vicky25,Filion Kristian B.236ORCID

Affiliation:

1. Department of Endocrinology & Metabolism McGill University Montreal Quebec Canada

2. Centre for Clinical Epidemiology, Lady Davis Institute Jewish General Hospital Montreal Quebec Canada

3. Department of Epidemiology, Biostatistics, and Occupational Health McGill University Montreal Quebec Canada

4. Division of Endocrinology and Metabolism Jewish General Hospital/McGill University Montreal Quebec Canada

5. Division of General Internal Medicine Jewish General Hospital/McGill University Montreal Quebec Canada

6. Department of Medicine McGill University Montreal Quebec Canada

Abstract

AimsThe cardiovascular benefits of sodium‐glucose cotransporter 2 inhibitors (SGLT2Is) result from their complex impact on coronary and arterial vessels. However, their effect on veins and the risk of venous thromboembolism (VTE) remains unclear. Meta‐analysis of trials has suggested no significant change in risk, but observational studies on the topic are scarce. Our objective was to determine if the use of SGLT2Is, compared to the use of dipeptidyl peptidase 4 inhibitors (DPP‐4Is), is associated with the risk of VTE among patients with type 2 diabetes.MethodsUsing the Clinical Practice Research Datalink linked to hospitalization and vital statistics databases, we conducted a retrospective cohort study using a prevalent new‐user design. SGLT2Is were matched to DPP‐4I users on calendar time, diabetes treatment intensity, duration of previous DPP‐4I use and time‐conditional high‐dimensional propensity score. Cox proportional hazard models estimated the hazard ratio (HR) for VTE with SGLT2Is versus DPP‐4Is.ResultsSGLT2I use was not associated with an increased risk of VTE (HR 0.65, 95% confidence interval [CI] 0.34 to 1.25). This finding was consistent among prevalent (HR 0.47, 95% CI 0.16 to 1.42) and incident (HR 0.75, 95% CI 0.33 to 1.72) new users.ConclusionsWe found that SGLT2Is were not associated with an increased risk of VTE compared to DPP‐4Is. Although we observed a numerically decreased risk of VTE with SGLT2Is, estimates were accompanied by wide 95% CIs. Nonetheless, given the morbidity associated with VTE, our results provide some reassurance regarding the safety of SGLT2Is with respect to VTE.

Publisher

Wiley

Subject

Pharmacology (medical),Pharmacology

Reference41 articles.

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2. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes

3. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes

4. Health Canada.SGLT2 inhibitors [INVOKANA (canagliflozin) FORXIGA (dapagliflozin) XIGDUO (dapagliflozin/metformin) JARDIANCE (empagliflozin)]—risk of diabetic ketoacidosis.2016. Accessed December 21 2018.http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2016/58404a-eng.php

5. US Food & Drug Administration.FDA Drug Safety Communication: FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections.2015.https://www.fda.gov/Drugs/DrugSafety/ucm475463.htm

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