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Sulfonylureas as second line drugs in type 2 diabetes and the risk of cardiovascular and hypoglycaemic events: population based cohort study.
BMJ. 2018 Jul 18; 362:k2693.BMJ

Abstract

OBJECTIVE

To assess whether adding or switching to sulfonylureas is associated with an increased risk of myocardial infarction, ischaemic stroke, cardiovascular death, all cause mortality, and severe hypoglycaemia, compared with remaining on metformin monotherapy in patients with type 2 diabetes.

DESIGN

Population based cohort study.

SETTING

General practices contributing data to the UK Clinical Practice Research Datalink.

PARTICIPANTS

Patients with type 2 diabetes initiating metformin monotherapy between 1998 and 2013.

MAIN OUTCOME MEASURES

Using the prevalent new-user cohort design we matched 1:1 patients adding or switching to sulfonylureas with those remaining on metformin monotherapy on high-dimensional propensity score, haemoglobin A1c, and number of previous metformin prescriptions. The two groups were compared using Cox proportional hazards models to estimate adjusted hazard ratios and 95% confidence intervals for the study outcomes.

RESULTS

Among 77 138 metformin initiators, 25 699 added or switched to sulfonylureas during the study period. During a mean follow-up of 1.1 years, sulfonylureas were associated with an increased risk of myocardial infarction (incidence rate 7.8 v 6.2 per 1000 person years, hazard ratio 1.26, 95% confidence interval 1.01 to 1.56), all cause mortality (27.3 v 21.5, 1.28, 1.15 to 1.44), and severe hypoglycaemia (5.5 v 0.7, 7.60, 4.64 to 12.44) compared with continuing metformin monotherapy. There was a trend towards increased risks of ischaemic stroke (6.7 v 5.5, 1.24, 0.99 to 1.56) and cardiovascular death (9.4 v 8.1, 1.18, 0.98 to 1.43). Compared with adding sulfonylureas, switching to sulfonylureas was associated with an increased risk of myocardial infarction (hazard ratio 1.51, 95% confidence interval, 1.03 to 2.24) and all-cause mortality (1.23, 1.00 to 1.50). No differences were observed for ischaemic stroke, cardiovascular death, or severe hypoglycaemia.

CONCLUSIONS

Sulfonylureas as second line drugs are associated with an increased risk of myocardial infarction, all cause mortality, and severe hypoglycaemia, compared with remaining on metformin monotherapy. Continuing metformin when introducing sulfonylureas appears to be safer than switching.

Authors+Show Affiliations

Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Ste-Catherine, H-461 Montréal, QC H3T 1E2, Canada. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montréal, QC, Canada. Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Ste-Catherine, H-461 Montréal, QC H3T 1E2, Canada.Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Ste-Catherine, H-461 Montréal, QC H3T 1E2, Canada. Division of Endocrinology, Jewish General Hospital, Montréal, QC, Canada.Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Ste-Catherine, H-461 Montréal, QC H3T 1E2, Canada. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montréal, QC, Canada. Division of Clinical Epidemiology, Department of Medicine, McGill University, Montréal, QC, Canada.Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Ste-Catherine, H-461 Montréal, QC H3T 1E2, Canada. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montréal, QC, Canada. Gerald Bronfman Department of Oncology, McGill University, Montréal, QC, Canada.Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Ste-Catherine, H-461 Montréal, QC H3T 1E2, Canada. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montréal, QC, Canada. Division of Clinical Epidemiology, Department of Medicine, McGill University, Montréal, QC, Canada.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30021781

Citation

Douros, Antonios, et al. "Sulfonylureas as Second Line Drugs in Type 2 Diabetes and the Risk of Cardiovascular and Hypoglycaemic Events: Population Based Cohort Study." BMJ (Clinical Research Ed.), vol. 362, 2018, pp. k2693.
Douros A, Dell'Aniello S, Yu OHY, et al. Sulfonylureas as second line drugs in type 2 diabetes and the risk of cardiovascular and hypoglycaemic events: population based cohort study. BMJ. 2018;362:k2693.
Douros, A., Dell'Aniello, S., Yu, O. H. Y., Filion, K. B., Azoulay, L., & Suissa, S. (2018). Sulfonylureas as second line drugs in type 2 diabetes and the risk of cardiovascular and hypoglycaemic events: population based cohort study. BMJ (Clinical Research Ed.), 362, k2693. https://doi.org/10.1136/bmj.k2693
Douros A, et al. Sulfonylureas as Second Line Drugs in Type 2 Diabetes and the Risk of Cardiovascular and Hypoglycaemic Events: Population Based Cohort Study. BMJ. 2018 Jul 18;362:k2693. PubMed PMID: 30021781.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sulfonylureas as second line drugs in type 2 diabetes and the risk of cardiovascular and hypoglycaemic events: population based cohort study. AU - Douros,Antonios, AU - Dell'Aniello,Sophie, AU - Yu,Oriana Hoi Yun, AU - Filion,Kristian B, AU - Azoulay,Laurent, AU - Suissa,Samy, Y1 - 2018/07/18/ PY - 2018/7/20/entrez PY - 2018/7/20/pubmed PY - 2019/3/5/medline SP - k2693 EP - k2693 JF - BMJ (Clinical research ed.) JO - BMJ VL - 362 N2 - OBJECTIVE: To assess whether adding or switching to sulfonylureas is associated with an increased risk of myocardial infarction, ischaemic stroke, cardiovascular death, all cause mortality, and severe hypoglycaemia, compared with remaining on metformin monotherapy in patients with type 2 diabetes. DESIGN: Population based cohort study. SETTING: General practices contributing data to the UK Clinical Practice Research Datalink. PARTICIPANTS: Patients with type 2 diabetes initiating metformin monotherapy between 1998 and 2013. MAIN OUTCOME MEASURES: Using the prevalent new-user cohort design we matched 1:1 patients adding or switching to sulfonylureas with those remaining on metformin monotherapy on high-dimensional propensity score, haemoglobin A1c, and number of previous metformin prescriptions. The two groups were compared using Cox proportional hazards models to estimate adjusted hazard ratios and 95% confidence intervals for the study outcomes. RESULTS: Among 77 138 metformin initiators, 25 699 added or switched to sulfonylureas during the study period. During a mean follow-up of 1.1 years, sulfonylureas were associated with an increased risk of myocardial infarction (incidence rate 7.8 v 6.2 per 1000 person years, hazard ratio 1.26, 95% confidence interval 1.01 to 1.56), all cause mortality (27.3 v 21.5, 1.28, 1.15 to 1.44), and severe hypoglycaemia (5.5 v 0.7, 7.60, 4.64 to 12.44) compared with continuing metformin monotherapy. There was a trend towards increased risks of ischaemic stroke (6.7 v 5.5, 1.24, 0.99 to 1.56) and cardiovascular death (9.4 v 8.1, 1.18, 0.98 to 1.43). Compared with adding sulfonylureas, switching to sulfonylureas was associated with an increased risk of myocardial infarction (hazard ratio 1.51, 95% confidence interval, 1.03 to 2.24) and all-cause mortality (1.23, 1.00 to 1.50). No differences were observed for ischaemic stroke, cardiovascular death, or severe hypoglycaemia. CONCLUSIONS: Sulfonylureas as second line drugs are associated with an increased risk of myocardial infarction, all cause mortality, and severe hypoglycaemia, compared with remaining on metformin monotherapy. Continuing metformin when introducing sulfonylureas appears to be safer than switching. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/30021781/Sulfonylureas_as_second_line_drugs_in_type_2_diabetes_and_the_risk_of_cardiovascular_and_hypoglycaemic_events:_population_based_cohort_study_ L2 - https://www.bmj.com/lookup/pmidlookup?view=long&pmid=30021781 DB - PRIME DP - Unbound Medicine ER -