Risk of hypoglycaemia in users of sulphonylureas compared with metformin in relation to renal function and sulphonylurea metabolite group: population based cohort studyBMJ 2016; 354 doi: https://doi.org/10.1136/bmj.i3625 (Published 13 July 2016) Cite this as: BMJ 2016;354:i3625
All rapid responses
Any insulin secretagogue has the potential of hypoglycemia, particularly with irregular dietary intake and renal insufficiency, as rightfully analysed and highlighted in the study.1 Hypoglycemia is a serious issue as it has short-term and long-term adverse outcomes.2 It must be avoided at any cost. However, the severity and frequency of hypoglycemia varies. Use of glibenclamide reduced rapidly in view of severe hypoglycemia. In view of its potential for severe and prolonged hypoglycemia, few people misused it for suicidal purposes. Glibenclamide inhibits myocardial preconditioning (a strong protective mechanism), therefore is counterproductive in contemporary cardiology practice. Glimperide, initially marketed as having both pancreatic and extra-pancreatic antidiabetic effects with less potential for hypoglycemia, was later on shown to have significant hypoglycemia as its side-effect.
Modified-release gliclazide has much less potential for severe hypoglycemia. In the ADVANCE trial, the intensive-control group (target Hb A1C 6.5%) and standard-control group (target HbA1C 7.3% at the end of the trial) had severe hypoglycemia 2.7% and 1.7% respectively. 3 Importantly it has less of a negative effect (glimperide has no negative effect) on protective (highly desirable particularly in diabetics) myocardial preconditioning, 4 thus making it rather safer and a preferred sulphonylurea. However, like metformin and other sulphonylurea drugs, caution must be exercised with these drugs as well in patients with renal insufficiency.
1. BMJ 2016;354:i3625
2.McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care 2012;35:1897–1900
3. Simon R. Heller, and on behalf of the ADVANCE Collaborative Group. A summary of the ADVANCE trial. Diabetes Care. 2009 Nov; 32(Suppl 2): S357–S361.
4.Wu GT, Wang L, Li J, et al. Effects of glibenclamide, glimperide, and gliclazide on ischemic pre-conditioning in rat heart. Chin Med Sci J. 2007 Sep;22(3):162-8.
Competing interests: No competing interests