Main Article Content

Pendar Farahani
Shahriar Khan
Mark Oatway
Alison Dziarmaga


Diabetes, pharmacotherapy, sulfonylurea, cardiovascular risk, Canadian population



A growing body of evidence generated from observational studies and meta-analyses has begun to illustrate the potential adverse cardiovascular (CV) risk profile associated with sulfonylurea (SU) use. Specifically, the use of an SU has been demonstrated to be associated with increased mortality and a higher risk of stroke with more CV events associated with SU use having been reported in subgroups of patients with a history of CV disease, elderly and a higher body mass index.


The objective of the current study was to explore the distribution of established atherosclerotic CV disease and CV risk factors amongst patients with diabetes on an SU using a Canadian primary care dataset for the 2013 calendar year.


The Canadian Primary Care Sentinel Surveillance Network (CPCSSN), which is a multi-disease surveillance system based on primary care electronic medical record data, was utilized for this research study. Patients with a diagnosis of diabetes and exposure to an SU were identified. Distribution/prevalence of CV risk profile amongst this sub- cohort was explored.


In analyzing the CPCSSN database for the 2013 calendar year, 6150 patients were identified as having diabetes, at least one visit with their family doctor, and on an SU. For this sub -cohort , demographic data was as follows: age [mean (SD)] 65.4(12.8) years -old; 56.4% male and mean BMI 31.3(10.0). Established atherosclerotic CV disease was observed in 16.8% of the patients with the following distribution: 13 .2% had ischemic heart disease/myocardial infarction or coronary artery disease; 2 .4% had stroke; and 2 .3% had peripheral vascular disease. Regarding the aggregation of CV risk factors, a large proportion (65%) of patients without established atherosclerotic CV disease presented with 2 or more CV risk factors including: hypertension (62%), dyslipidemia (33%), active smoking (13%), and obesity (43%). Almost half of the cohort (45%) were males older than 55 years of age or females older than 60 years of age with at least one of the following risk factors: dyslipidemia, hypertension or current smoking, but without established cardiovascular disease. A large proportion of patients (19.5%) had a diagnosis of cardiac-specific issues including ischemic heart disease /myocardial infarction/coronary artery disease, heart failure (not due to ischemic heart disease /myocardial infarction/coronary artery disease ), or arrhythmia. Almost 82% of patients had either established atherosclerotic CV disease or 2 or more CV risk factors without established atherosclerotic CV disease.


This study illustrated that in this dataset of Canadian patients with diabetes in a primary care setting, a substantial proportion of patients treated with an SU in 2013 had established CV disease and/or an aggregation of multiple CV risk factors. In light of recent data reporting on an association between SU utilization and CV events and increased mortality, pharmacovigilance programs should actively monitor SU utilization in patients with diabetes and a high risk CV profile in real world clinical settings.

Abstract 116 | PDF Downloads 65


1. Canadian Diabetes Association. Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Can J Diabetes 2013;37:S1- S212.
2. Inzucchi SE, Bergenstal RM, Buse JB , et al. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 2015;58:429- 42.
3. Genuth S. Should sulfonylureas remain an acceptable first-line add -on to metformin therapy in patients with type 2 diabetes? No, it's time to move on! Diabetes Care 2015;38:170- 5.
4. Abrahamson MJ. Should sulfonylureas remain an acceptable first-line add -on to metformin therapy in patients with type 2 diabetes? Yes, they continue to serve us well! Diabetes Care 2015;38:166 -9.
5. Panicker GK, Karnad DR, Salvi V, Kothari S. Cardiovascular risk of oral antidiabetic drugs: current evidence and regulatory requirements for new drugs. J Assoc Physicians India 2012;60:56- 61.
6. Singh S, Bhat J, Wang PH. Cardiovascular effects of anti-diabetic medications in type 2 diabetes mellitus. Curr Cardiol Rep 2013;15:327.
7. Simpson SH, Majumdar SR, Tsuyuki RT, Eurich DT, Johnson JA. Dose-response relation between sulfonylurea drugs and mortality in type 2 diabetes mellitus: a population-based cohort study. CMAJ 2006;174:169- 74.
8. Riveline JP, Danchin N, Ledru F, Varroud - Vial M, Charpentier G. Sulfonylureas and cardiovascular effects: from experimental data to clinical use. Available data in humans and clinical applications. Diabetes Metab 2003;29:207- 22.
9. Roumie CL, Hung AM, Greevy RA, et al. Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study. Ann Intern Med 2012;157:601- 10.
10. Monami M, Genovese S, Mannucci E. Cardiovascular safety of sulfonylureas: a meta-analysis of randomized clinical trials. Diabetes Obes Metab 2013;15:938- 53.
11. Engler RL, Yellon DM. Sulfonylurea KATP blockade in type II diabetes and preconditioning in cardiovascular disease. Time for reconsideration. Circulation 1996;94:2297- 301.
12. Standards of medical care in diabetes -2015 abridged for primary care providers. Clin Diabetes 2015;33:97- 111.
13. "Drug use in older people with diabetes." Diabetes in Ontario: an ICES practice atlas 2003; Chapter 3:3.51- 3.76.
14. Mashayekhi M, Prescod F, Shah B, Dong L, Keshavjee K, Guergachi A. Evaluating the performance of the Framingham Diabetes Risk Scoring Model in Canadian electronic medical records. Can J Diabetes 2015;39:152- 6.
15. Kadhim -Saleh A, Green M, Williamson T, Hunter D, Birtwhistle R. Validation of the diagnostic algorithms for 5 chronic conditions in the Canadian Primary Care Sentinel Surveillance Network (CPCSSN): a Kingston Practice-based Research Network (PBRN) report. J Am Board Fam Med 2013;26:159- 67.
16. Greiver M, Williamson T, Barber D, et al. Prevalence and epidemiology of diabetes in Canadian primary care practices: a report from the Canadian Primary Care Sentinel Surveillance Network. Can J Diabetes 2014;38:179- 85.
17. Williamson T, Green ME, Birtwhistle R, et al. Validating the 8 CPCSSN case definitions for chronic disease surveillance in a primary care database of electronic health records. Ann Fam Med 2014;12:367- 72.
18. Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013;369:1317- 26.
19. Hemmingsen B, Schroll JB, Wetterslev J, et al. Sulfonylurea versus metformin monotherapy in patients with type 2 diabetes: a Cochrane systematic review and meta-analysis of randomized clinical trials and trial sequential analysis. CMAJ Open 2014;2:E162- E175.
20. Forst T, Hanefeld M, Jacob S , et al. Association of sulphonylurea treatment with all-cause and cardiovascular mortality: a systematic review and meta-analysis of observational studies. Diab Vasc Dis Res 2013;10:302- 14.
21. Rados D, Ponto L, Remonti L. Sulfonylureas are not associated with increased mortality: Meta-analysis and trial sequential analysis of randomized clinical trials. Ameri can Diabetes Association 2015 Scientific Sessions; June 6, 2015; Boston, MA Abstract 16- OR 2015.
22. Bloomgarden ZT, Einhorn D. Hypoglycemia in type 2 diabetes: current controversies and changing practices. Front Endocrinol (Lausanne) 2012;3:66.
23. Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care 2013;36:1384- 95.
24. Alvarez GF, Tofe PS, Krishnarajah G, Lyu R, Mavros P, Yin D. Hypoglycaemic symptom s, treatment satisfaction, adherence and their associations with glycaemic goal in patients with type 2 diabetes mellitus: findings from the Real-Life Effectiveness and Care Patterns of Diabetes Management (RECAP -DM) Study. Diabetes Obes Metab 2008;10 Suppl 1:25- 32.
25. Alvarez GF, Mavros P, Nocea G, Alemao E, Alexander CM, Yin D. Glycaemic control among patients with type 2 diabetes mellitus in seven European countries: findings from the Real-Life Effectiveness and Care Patterns of Diabetes Management (RECAP -DM) study. Diabetes Obes Metab 2008;10 Suppl 1:8 -15.
26. Brod M, Christensen T, Bushnell DM. Impact of nocturnal hypoglycemic events on diabetes management, sleep quality, and next-day function: results from a four-country survey. J Med Econ 2012;15:77- 86.
27. Brod M, Pohlman B, Wolden M, Christensen T. Non -severe nocturnal hypoglycemic events: experience and impacts on patient functioning and well -being. Qual Life Res 2013;22:997- 1004.
28. Green AJ, Fox KM, Grandy S. Self -reported hypoglycemia and impact on quality of life and depression among adults with type 2 diabetes mellitus. Diabetes Res Clin Pract 2012;96:313- 8.
29. Farmer AJ, Brockbank KJ, Keech ML, England EJ, Deakin CD. Incidence and costs of severe hypoglycaemia requiring attendance by the emergency medical services in South Central England. Diabet Med 2012;29:1447- 50.
30. Inzucchi SE, Bergenstal RM, Buse JB , et al. Management of hyperglycemia in type 2 diabetes: a patient -centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012;35:1364- 79.
31. Gross JL, Kramer CK, Lei tao CB, et al. Effect of antihyperglycemic agents added to metformin and a sulfonylurea on glycemic control and weight gain in type 2 diabetes: a network meta-analysis. Ann Intern Med 2011;154:672- 9.
32. McIntosh B, Cameron C, Singh SR, Yu C, Dolovich L, Hould en R. Choice of therapy in patients with type 2 diabetes inadequately controlled with metformin and a sulphonylurea: a systematic review and mixed -treatment comparison meta- analysis. Open Med 2012;6:e62- e74.
33. Lau DC, Douketis JD, Morrison KM, Hramiak IM, Sh arma AM, Ur E. 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children [summary]. CMAJ 2007;176:S1- 13.
34. Anderson JW, Kendall CW, Jenkins DJ. Importance of weight management in type 2 diabetes: review wit h meta -analysis of clinical studies. J Am Coll Nutr 2003;22:331- 9.
35. Twells LK, Gregory DM, Reddigan J, Midodzi WK. Current and predicted prevalence of obesity in Canada: a tr end analysis. CMAJ Open 2014;2: e18- e26.

Most read articles by the same author(s)