The mode of action and clinical pharmacology of gliclazide: a review

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Abstract

Gliclazide is a sulphonylurea drug with an intermediate half-life of around 11 hours. It is extensively metabolised, and renal clearance accounts for only 4% of total drug clearance. The molecule contains an azabicyclo-octyl group which confers special properties on the basic sulphonylurea moiety. Gliclazide stimulates insulin secretion through the β cell sulphonylurea receptor, and possibly through a direct effect on intracellular calcium transport. It specifically improves the abnormal first phase insulin release in type 2 diabetes, and also has an effect on the second phase. This pattern of insulin release is thought to explain the lower incidence of hypoglycaemic episodes and weight gain compared with some other sulphonylureas. There is also a reduction in hepatic glucose production and improvement in glucose clearance, without changes in insulin receptors. This suggests a possible post-receptor effect on insulin action, perhaps by stimulation of hepatic fructose-2,6-bisphosphatase and muscle glycogen synthase. Gliclazide reduces platelet adhesion, aggregation and hyperactivity and increases fibrinolysis. These actions, thought to be independent of its hypoglycaemic activity, may make gliclazide useful in halting the progression of diabetic microangiopathy.

References (117)

  • M. Lagarde et al.

    Effects of gliclazide, a new antidiabetic agent, on the platelet release reaction, role of adenylate cyclase

    Thromb. Res.

    (1975)
  • M.M. Bern

    Platelet functions in diabetes mellitus

    Diabetes

    (1978)
  • B. Haitas et al.

    Abnormal endothelial release of fibrinolytic activity and fibronectin in diabetic microangiography

    Diabetologia

    (1984)
  • S.M. MacRury et al.

    Blood rheology in diabetes mellitus

    Diabetic Med.

    (1990)
  • L.G. Beregi

    Structural aspects of sulphonylureas

  • D.B. Campbell et al.

    Pharmacokinetics and metabolism of gliclazide: a review

  • A. Igaki et al.

    High-performance liquid chromatographic determination of gliclazide (oral hypoglycemic agent) in serum. Attempt at sensitive fluorometric determination

    Jpn. J. Clin. Path. (Rinsho Byori)

    (1986)
  • H. Kajinuma et al.

    Radioimmunoassay of gliclazide in serum. II. Changes in serum levels after oral administration

    J. Jpn. Diabetes Soc. (Tongobyo)

    (1982)
  • S. Yokoh et al.

    Study on the anti-diabetic effect of gliclazide

    J. Kyoto Prof., University Med.

    (1982)
  • K. Shima et al.

    Effect of dietary fibre, konjac mannan and guar gum, on absorption of sulphonylurea in man

    Nutr. Rep. Int.

    (1982)
  • F. Ishibashi et al.

    The effect of timing on gliclazide absorption and action

    Hiroshima J. Med. Sci.

    (1990)
  • J. Batch et al.

    The effects of ingestion time of gliclazide in relationship to meals on plasma glucose, insulin and C-peptide levels

    Eur. J. Clin. Pharmacol.

    (1990)
  • S. Nakano et al.

    Effects of dosing regimen of oral hypoglycemic drug, gliclazide, on blood glucose and insulin levels

    Eur. J. Clin. Pharmacol.

    (1989)
  • T. Fujii et al.

    Drug interactions of gliclazide and other sulphonylureas in protein binding in vitro and in hypoglycaemic effects in rats

    Arzneimittel-Forschung Drug Res.

    (1983)
  • A. Melander et al.

    Sulphonylurea antidiabetic drugs. An update of their clinical pharmacology and rational therapeutic use

    Drugs

    (1989)
  • F. Archambeaud-Monveroux et al.

    Interaction between gliclazide and cimetidine

    Eur. J. Clin. Pharmacol.

    (1987)
  • J. Feely et al.

    Enhanced sulphonylurea-induced hypoglycaemia with cimetidine

    Br. J. Clin. Pharmacol.

    (1983)
  • T. Oida et al.

    The metabolism of gliclazide in man

    Xenobiotica

    (1985)
  • J. Boutagy et al.

    Gliclazide metabolic clearance in debrisoquine phenotyped subjects: comparison with tolbutamide

    Clin. Exp. Pharmacol. Physiol.

    (1987)
  • B. Forret et al.

    Gliclazide pharmacokinetics in the elderly

  • K.M. Shaw et al.

    Home blood glucose monitoring in non-insulin-dependent diabetics: the effect of gliclazide on blood glucose and weight control

    Diabetic Med.

    (1985)
  • D.B. Campbell et al.

    The effects of renal disease on the pharmacokinetics of gliclazide in diabetic patients

    Br. J. Clin. Pharmacol.

    (1986)
  • D.B. Campbell et al.

    Biodisposition and pharmacodynamics of gliclazide in man

  • D.B. Campbell

    The use of kinetic-dynamic interactions in the evaluation of drugs

    Psychopharmacology

    (1990)
  • S.-E. Fagerberg et al.

    Paired observations between different sulphonylureas in antidiabetic treatment

  • K. Kobayashi et al.

    Influence of blood proteins on biomedical analysis. (II) Interaction of gliclazide with bovine serum albumin

    Chem. Pharm. Bull.

    (1981)
  • B.J. Martin et al.

    Dietary control of elderly diabetic patients — a case for review

    Pract. Diabetes

    (1986)
  • R.C. Paton et al.

    Effects of diet and gliclazide on the haemostatic system in maturity-onset diabetes

  • D.B. Campbell et al.

    Can plasma gliclazide concentrations explain its mode of action?

  • B. Holmes et al.

    A preliminary review of its pharmacodynamic properties and therapeutic efficacy in diabetes mellitus

    Drugs

    (1984)
  • J. Zurro-Hernandez et al.

    Is sulphonylurea therapy effective long term? A 3-year study with gliclazide

    Curr. Med. Res. Opin.

    (1986)
  • P.J. Guillausseau et al.

    HbA in long term evaluation of glycemic control

    Am. J. Med.

    (1991)
  • C. Kilo et al.

    Evaluation of safety and efficacy of gliclazide in non-insulin-dependent diabetic patients

    Bull. Int. Diabetes Fed.

    (1987)
  • G.H. Robb et al.

    Lack of weight gain with gliclazide treatment for 30 months in type II diabetes

    Curr. Med. Res. Opin.

    (1984)
  • A.D. Harrower

    Comparison of diabetic control in Type 2 (non-insulin) diabetic patients treated with different sulfonylureas

    Curr. Med. Res. Opin.

    (1985)
  • J.P. Donnet

    Evaluation métabolique et pondérale de l'efficacité à long terme du Diamicron dans le diabète non insulino-dépendant

    Vie Med.

    (1982)
  • J.M. Oli

    Treatment with gliclazide (Diamicron) in obese Nigerian diabetics

    Curr. Ther. Res.

    (1980)
  • J.L. Chiasson et al.

    Insulin regulation of glucogenesis in man

    Diabetes

    (1979)
  • A. Beck-Neilsen et al.

    Mechanism of action of sulphonylureas with special reference to the extrapancreatic effect: an overview

    Diabetic Med.

    (1988)
  • B.L. Wajchenberg et al.

    Effect of gliclazide treatment on red blood cell insulin receptors, hepatic glucose production and peripheral glucose utilisation in non-insulin-dependent diabetes mellitus

    Bull. Int. Diabetes Fed.

    (1987)
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