Published: 2 June 2016

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Sulfonylureas – Associated with Cardiovascular Disease?

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Prescriber Update 37(2): 18-19
June 2016

Sulfonylureas increase insulin release from pancreatic beta cells and are used to manage type 2 diabetes¹. Glibenclamide, glipizide and gliclazide are approved and funded for use in New Zealand.

In general, sulfonylureas are used in addition to metformin in patients who have failed to reach target HbA1c levels. However, a sulfonylurea may also be used as monotherapy in patients intolerant of metformin^1,2.

The effect of different anti-diabetic medicines on cardiovascular outcomes is of significant interest. The Medicines Adverse Reactions Committee (MARC) recently reviewed the available scientific information on cardiovascular outcomes in patients managed with sulfonylureas (www.medsafe.govt.nz/profs/adverse/Minutes165.htm).

Information on cardiovascular outcomes in patients participating in randomised controlled trials of sulfonylureas is generally lacking. However, the SPREAD-DIMCAD study, which compared glipizide and metformin management in Chinese patients, did measure this outcome³. Patients in the metformin group had fewer adverse cardiovascular events than those taking glipizide.

The interpretation of published observational studies in which cardiovascular outcomes are examined is limited by several factors. For example, in many studies there was a lack of information on confounding factors such as smoking status. In addition, patients managed with metformin were different to those taking sulfonylureas, as evidenced by the difference in baseline characteristics.

The MARC concluded that the available data were sufficient to determine that glibenclamide is associated with a higher risk of adverse cardiovascular outcomes than glipizide or gliclazide. It was also noted that glibenclamide is associated with a higher risk of hypoglycaemia than glipizide or gliclazide, which are the preferred sulfonylureas².

References

1. Pfizer New Zealand Limited. 2008. Minidiab Data Sheet 20 June 2008. URL: www.medsafe.govt.nz/profs/Datasheet/m/Minidiabtab.pdf (accessed 8 April 2016).
2. Best Practice Advocacy Centre New Zealand. 2015. Managing patients with type 2 diabetes: from lifestyle to insulin. Best Practice Journal 72: 32-42. URL: www.bpac.org.nz/BPJ/2015/December/docs/BPJ72-diabetes.pdf (accessed 8 April 2016).
3. Hong J, Zhang Y, Lai S, et al. 2013. Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease. Diabetes Care 36: 1304-1311.