136 © 2002 Diabetes UK. Diabetic Medicine, 19, 136 –143 Introduction Type 2 diabetes mellitus is an important cardiovascular risk factor [1,2], which is often treated with sulphonylurea derivat- ives [3]. These drugs close ATP-dependent potassium (K ATP ) channels in the β-cells of the pancreas with subsequent stimu- lation of insulin release [4]. As recently demonstrated, func- tional K ATP channels are also present in the vascular system [5,6]. Under physiological circumstances these channels are in a closed or inactive state [7], but during hypoxia and / or isch- aemia, the fall in intracellular ATP concentration triggers opening of K ATP channels. The resulting potassium efflux and hyperpolarization of the cell membrane induces shortening of the action potential in the myocardium and relaxation of the Correspondence to : P. Smits MD, PhD, Professor of Pharmacology, Department of Pharmacology—Toxicology 233, University Medical Centre Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail: P.Smits@farm.kun.nl Abstract Aims Glibenclamide attenuates the protective responses to opening of vascu- lar ATP-sensitive potassium (K ATP ) channels during ischaemia. Therefore, glibenclamide treatment of Type 2 diabetes mellitus may have hazardous cardio- vascular effects when used under conditions of ischaemia. Glimepiride and metformin seem to lack such characteristics. Based on these data, we hypothesized that, in contrast to glibenclamide, chronic treatment of Type 2 diabetic patients with glimepiride or metformin will not impair the vasodilator function of K ATP opening in vivo. Methods Two groups of 12 Type 2 diabetes mellitus patients participated in a double-blind randomized cross-over study consisting of two 8-week periods, in which treatment with orally administered glibenclamide (15 mg / day) was compared with either glimepiride or metformin (6 mg and 1500 mg / day, respect- ively). At the end of each treatment period, the increase in forearm blood flow (FBF, venous occlusion plethysmography) in response to intra-arterial admin- istered diazoxide (K ATP opener), acetylcholine (endothelium-dependent vaso- dilator) and dipyridamole (adenosine-uptake blocker) and to forearm ischaemia was measured. Results There were no significant differences in vasodilator responses to diazoxide, acetylcholine, dipyridamole and forearm ischaemia after glibenclamide compared with glimepiride and metformin. Conclusions Chronic treatment of Type 2 diabetes mellitus with glimepiride or metformin has similar effects on vascular K ATP channels compared with chronic glibenclamide treatment. Diabet. Med. 19, 136 –143 (2002) Keywords glibenclamide, glimepiride, metformin, K ATP channels, venous occlusion plethysmography Abbreviations FBF, forearm blood flow; K ATP channel, ATP-dependent potassium channel Blackwell Science Ltd Oxford, UK DME Diabetic Medicine 0742-3071 Blackwell Science Ltd, 2001 2002 19 1 000 Original Article Original article Vascular effects of glibenclamide vs. glimepiride and metformin E. J. Abbink et al. Vascular effects of glibenclamide vs. glimepiride and metformin in Type 2 diabetic patients E. J. Abbink*, P. Pickkers*, A. Jansen van Rosendaal*, J. A. Lutterman*, C. J. Tack*, F. G. M. Russel† and P. Smits*† *Division of General Internal Medicine, Department of Medicine, and †Department of Pharmacology — Toxicology, University Medical Centre Nijmegen, Nijmegen, The Netherlands Accepted 26 August 2001