Kristian B Filion1,2,3, Antonios Douros2,3,4,5, Laurent Azoulay2,3,6, Hui Yin2, Oriana H Yu2,7, Samy Suissa1,2,3. 1. Department of Medicine, McGill University, Montreal, Quebec, Canada. 2. Center 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. Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. 5. Berlin Institute of Health, Berlin, Germany. 6. Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada. 7. Division of Endocrinology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
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.
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.
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Authors: Kristian B Filion; Lisa M Lix; Oriana Hy Yu; Sophie Dell'Aniello; Antonios Douros; Baiju R Shah; Audray St-Jean; Anat Fisher; Eric Tremblay; Shawn C Bugden; Silvia Alessi-Severini; Paul E Ronksley; Nianping Hu; Colin R Dormuth; Pierre Ernst; Samy Suissa Journal: BMJ Date: 2020-09-23