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Sulfonylureas as initial treatment for type 2 diabetes and the risk of adverse cardiovascular events: A population-based cohort study.
Br J Clin Pharmacol. 2019 10; 85(10):2378-2389.BJ

Abstract

AIMS

Sulfonylureas are recommended as second-line treatment in the management of type 2 diabetes. However, they are still commonly used also as first-line treatment instead of metformin. Given the controversial cardiovascular safety of sulfonylureas, we aimed to determine if their use as first-line treatment is associated with adverse cardiovascular events among patients with newly treated type 2 diabetes compared with metformin.

METHODS

We conducted a population-based cohort study of patients with newly treated type 2 diabetes using the UK's Clinical Practice Research Datalink. Initiators of metformin and sulfonylurea monotherapy were matched on high-dimensional propensity score, and Cox proportional hazards models were used to compare the rate of cardiovascular events (myocardial infarction, ischaemic stroke, cardiovascular death, and all-cause mortality) with sulfonylureas vs metformin.

RESULTS

Our cohort included 94 750 patients initiating treatment for type 2 diabetes, 17 612 on a sulfonylurea and 77 138 on metformin. After matching, sulfonylurea monotherapy, compared with metformin monotherapy, was not associated with an increased risk of myocardial infarction (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 0.85-1.25) but was associated with increased risks of ischaemic stroke (HR: 1.25, 95% CI: 1.002-1.56), cardiovascular death (HR: 1.25, 95% CI: 1.06-1.47), and all-cause mortality (HR: 1.60, 95% CI: 1.45-1.76). This represents an additional 2.0 ischaemic strokes, 3.5 cardiovascular deaths, and 21.4 all-cause deaths per 1,000 patients per year with sulfonylureas.

CONCLUSIONS

Initiating treatment of type 2 diabetes with a sulfonylurea rather than metformin is associated with higher rates of ischaemic stroke, cardiovascular death, and all-cause mortality.

Authors+Show Affiliations

Department of Medicine, McGill University, Montreal, Quebec, Canada. Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada.Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada. Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. Berlin Institute of Health, Berlin, Germany.Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada. Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada.Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada. Division of Endocrinology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.Department of Medicine, McGill University, Montreal, Quebec, Canada. Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31276600

Citation

Filion, Kristian B., et al. "Sulfonylureas as Initial Treatment for Type 2 Diabetes and the Risk of Adverse Cardiovascular Events: a Population-based Cohort Study." British Journal of Clinical Pharmacology, vol. 85, no. 10, 2019, pp. 2378-2389.
Filion KB, Douros A, Azoulay L, et al. Sulfonylureas as initial treatment for type 2 diabetes and the risk of adverse cardiovascular events: A population-based cohort study. Br J Clin Pharmacol. 2019;85(10):2378-2389.
Filion, K. B., Douros, A., Azoulay, L., Yin, H., Yu, O. H., & Suissa, S. (2019). Sulfonylureas as initial treatment for type 2 diabetes and the risk of adverse cardiovascular events: A population-based cohort study. British Journal of Clinical Pharmacology, 85(10), 2378-2389. https://doi.org/10.1111/bcp.14056
Filion KB, et al. Sulfonylureas as Initial Treatment for Type 2 Diabetes and the Risk of Adverse Cardiovascular Events: a Population-based Cohort Study. Br J Clin Pharmacol. 2019;85(10):2378-2389. PubMed PMID: 31276600.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sulfonylureas as initial treatment for type 2 diabetes and the risk of adverse cardiovascular events: A population-based cohort study. AU - Filion,Kristian B, AU - Douros,Antonios, AU - Azoulay,Laurent, AU - Yin,Hui, AU - Yu,Oriana H, AU - Suissa,Samy, Y1 - 2019/07/31/ PY - 2018/11/22/received PY - 2019/06/07/revised PY - 2019/06/17/accepted PY - 2019/7/6/pubmed PY - 2020/9/24/medline PY - 2019/7/6/entrez KW - myocardial infarction KW - pharmacoepidemiology KW - stroke KW - sulfonylureas KW - type 2 diabetes SP - 2378 EP - 2389 JF - British journal of clinical pharmacology JO - Br J Clin Pharmacol VL - 85 IS - 10 N2 - AIMS: Sulfonylureas are recommended as second-line treatment in the management of type 2 diabetes. However, they are still commonly used also as first-line treatment instead of metformin. Given the controversial cardiovascular safety of sulfonylureas, we aimed to determine if their use as first-line treatment is associated with adverse cardiovascular events among patients with newly treated type 2 diabetes compared with metformin. METHODS: We conducted a population-based cohort study of patients with newly treated type 2 diabetes using the UK's Clinical Practice Research Datalink. Initiators of metformin and sulfonylurea monotherapy were matched on high-dimensional propensity score, and Cox proportional hazards models were used to compare the rate of cardiovascular events (myocardial infarction, ischaemic stroke, cardiovascular death, and all-cause mortality) with sulfonylureas vs metformin. RESULTS: Our cohort included 94 750 patients initiating treatment for type 2 diabetes, 17 612 on a sulfonylurea and 77 138 on metformin. After matching, sulfonylurea monotherapy, compared with metformin monotherapy, was not associated with an increased risk of myocardial infarction (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 0.85-1.25) but was associated with increased risks of ischaemic stroke (HR: 1.25, 95% CI: 1.002-1.56), cardiovascular death (HR: 1.25, 95% CI: 1.06-1.47), and all-cause mortality (HR: 1.60, 95% CI: 1.45-1.76). This represents an additional 2.0 ischaemic strokes, 3.5 cardiovascular deaths, and 21.4 all-cause deaths per 1,000 patients per year with sulfonylureas. CONCLUSIONS: Initiating treatment of type 2 diabetes with a sulfonylurea rather than metformin is associated with higher rates of ischaemic stroke, cardiovascular death, and all-cause mortality. SN - 1365-2125 UR - https://www.unboundmedicine.com/medline/citation/31276600/Sulfonylureas_as_initial_treatment_for_type_2_diabetes_and_the_risk_of_adverse_cardiovascular_events:_A_population_based_cohort_study_ L2 - https://doi.org/10.1111/bcp.14056 DB - PRIME DP - Unbound Medicine ER -