Skip to main content

Advertisement

SpringerLink
Log in

Characteristics and time course of severe glimepiride- versus glibenclamide-induced hypoglycaemia

  • Pharmacodynamics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

To compare the clinical characteristics and time course of severe hypoglycaemia (SH) on glimepiride and the reference drug glibenclamide.

Methods

SH was defined as a symptomatic event requiring administration of i.v. glucose or of glucagon. Four hundred doctors working in acute care hospitals were randomly selected from the membership directory of the German Diabetes Association and sent a standardised questionnaire about sulphonylurea-induced SH that occurred between June 2001 and August 2002. Detailed data on history, medication, laboratory parameters, treatment and time course of the SH were analysed.

Results

Altogether, 93 episodes of SH were registered, 37 on glimepiride and 56 on glibenclamide. The characteristics of the glimepiride- versus glibenclamide-induced SH were as follows: initial blood glucose 1.9±0.66 mmol/l versus 1.8±0.89 mmol/l, P=0.17; age 77±11.2 years versus 78±9.6 years, P=0.35; HbA1c 5.4±0.7% versus 5.2±0.9%, P=0.18; creatinine clearance 38±23 ml/min versus 54±32 ml/min, P=0.005; co-medication 6.2.±3 versus 3.6±3 preparations, P< 0.0001. Even very low doses of glimepiride (0.5 mg) and glibenclamide (0.88 mg) were associated with SH. Prolonged hypoglycaemia requiring more than 12 h i.v. glucose administration occurred in 8 of 37 of the glimepiride-treated subjects and 5 of 56 of those on glibenclamide. Prolonged hypoglycaemia necessitated infusion of 308±256 g (104–862 g) i.v. glucose over 43±16 h (24–64 h) in glimepiride-treated patients compared with 168±98 g (66–300 g) over 33±28 h (14–80 h) in glibenclamide-treated patients. Impaired renal function was present in 11 of 13 of all patients with prolonged hypoglycaemia and impaired liver function in 1 of 13.

Conclusion

In glimepiride- and glibenclamide-treated individuals with SH, no essential differences in the clinical characteristics or time course were shown; prolonged courses also occurred on glimepiride. Even in patients with only mild renal failure both preparations should be used with caution.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.

Similar content being viewed by others

References

  1. Asplund K, Wiholm B-E, Lithner F (1983) Glibenclamide-associated hypoglycaemia: a report on 57 cases. Diabetologia 24:412–417

    CAS  PubMed  Google Scholar 

  2. Holstein A, Plaschke A, Egberts E-H (2001) Lower incidence of severe hypoglycaemia in Type 2 diabetic patients treated with glimepiride versus glibenclamide. Diabetes Metab Res Rev 17:467–473

    Article  CAS  PubMed  Google Scholar 

  3. Ben-Ami H, Nagachandran P, Mendelson A, Edoute Y (1999) Drug-induced hypoglycemic coma in 102 diabetic patients. Arch Intern Med 159:281–284

    Article  CAS  PubMed  Google Scholar 

  4. Stahl M, Berger W (1999) Higher incidence of severe hypoglycaemia leading to hospital admission in type 2 diabetic patients treated with long-acting versus short-acting sulphonylureas. Diabetes Med 16:586–590

    Article  CAS  Google Scholar 

  5. Sugarman JR (1991) Hypoglycemia associated hospitalizations in a population with a high prevalence of non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 14:139–148

    CAS  PubMed  Google Scholar 

  6. Bachmann W, Löbe A, Lacher F (1995) Medikamentös bedingte Hypoglykämien bei Typ-II-Diabetes. Diabetes und Stoffwechsel 4:83–89

    Google Scholar 

  7. Rydberg T, Wählin-Boll E, Melander A (1991) Determination of glibenclamide and its two major metabolites in human serum and urine by column liquid chromatography. J Chromatogr 564:223–233

    CAS  PubMed  Google Scholar 

  8. Balant L, Zahnd GR, Weber F, Fabre J (1977) Behaviour of glibenclamide on repeated administration to diabetic patients. Eur J Clin Pharmacol 11:19–25

    CAS  PubMed  Google Scholar 

  9. Hellman B, Schlin J, Täljedal IB (1984) Glibenclamide is exceptional among in hypoglycaemic sulphonylureas in accumulating progressively in β-cell-rich islets. Acta Endocrinol 105:385–390

    CAS  PubMed  Google Scholar 

  10. Rydberg T, Jönsson A, Roder M, Melander A (1994) Hypoglycemic activity of glyburide (glibenclamide) metabolites in humans. Diabetes Care 17:1026–1030

    CAS  PubMed  Google Scholar 

  11. Alexander RW (1966) Prolonged hypoglycemia following acetohexamide administration. Report on two cases with impaired renal function. Diabetes 15:362–364

    CAS  PubMed  Google Scholar 

  12. Sonnenblick M, Shilo S (1986) Glibenclamide induced prolonged hypoglycaemia. Age Ageing 15:185–189

    CAS  PubMed  Google Scholar 

  13. Sills MN, Ogu CC, Maxa J (1997) Prolonged hypoglycemic crisis associated with glyburide. Pharmacotherapy 17:1338–1340

    CAS  PubMed  Google Scholar 

  14. Krepinsky J, Ingram AJ, Clase CM (2000) Prolonged sulfonylurea-induced hypoglycemia in diabetic patients with end-stage renal disease. Am J Kidney Dis 35:500–505

    CAS  PubMed  Google Scholar 

  15. Müller G, Hartz D, Pünter J, Ökonomopulos R, Kramer W (1994) Differential interaction of glimepiride and glibenclamide with the β-cell-sulfonylurea receptor. I. Binding characteristics. Biochim Biophys Acta 1191:267–277

    PubMed  Google Scholar 

  16. Kramer W, Müller G, Geisen K (1996) Characterization of the molecular mode of action of the sulfonylurea, glimepiride, at β-cells. Horm Metab Res 28:464–468

    CAS  PubMed  Google Scholar 

  17. DCCT Research Group (1991) Epidemiology of severe hypoglycaemia in the Diabetic Control and Complication Trial. Am J Med 90:450–459

    PubMed  Google Scholar 

  18. Cockroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41

    CAS  PubMed  Google Scholar 

  19. Joost H-G, Mengel K (2002) Antidiabetika. In: Schwabe U, Paffrath D (eds) Arzneiverordnungs-Report 2001. Springer, Berlin Heidelberg New York, pp 163–177

  20. Song DK, Ashcroft FM (2001) Glimepiride block of cloned beta-cell, cardiac and smooth muscle K (ATP) channels. Br J Pharmacol 133:193–199

    CAS  PubMed  Google Scholar 

  21. Draeger KE, Wernicke-Panten K, Lomp, H-J, Schuler E, Roßkamp R (1996) Long-term treatment of type 2 diabetic patients with the new oral antidiabetic agent glimepiride (Amaryl): a double-blind comparison with glibenclamide. Horm Metab Res 28:419–425

    CAS  PubMed  Google Scholar 

  22. Dills DG, Schneider J, The Glimepiride/Glyburide Research Group (1996) Clinical evaluation of glimepiride versus glyburide in NIDDM in a double-blind comparative study. Horm Metab Res 28:426–429

    CAS  PubMed  Google Scholar 

  23. Raptis SA, Hatziagelaki E, Dimitriadis G, Draeger KE, Pfeiffer C, Raptis AE (1999) Comparative effects of glimepiride and glibenclamide on blood glucose, C-peptide and insulin concentrations in the fasting and postprandial state in normal man. Exp Clin Endocrinol Diabetes 107:350–355

    CAS  PubMed  Google Scholar 

  24. Müller G, Satoh Y, Geisen K (1995) Extrapancreatic effects of sulfonylureas—a comparison between glimepiride and conventional sulfonylureas. Diabetes Res Clin Pract 28[Suppl]:S115–S137

  25. Haupt A, Kausch C, Dahl D, Bachmann O, Stumvoll M, Häring H, Matthaei S (2002) Effect of glimepiride on insulin-stimulated glucogen synthesis in cultured human skeletal muscle cells: a comparison to glibenclamide. Diabetes Care 25:2129–2132

    CAS  PubMed  Google Scholar 

  26. Rosenkranz B, Profozic V, Metelko Z, Mrzljak V, Lange C, Malerczyk V (1996) Pharmacokinetics and safety of glimepiride at clinically doses in diabetic patients with renal impairment. Diabetologia 39:1617–1624

    Article  CAS  PubMed  Google Scholar 

  27. Badian M, Korn A, Lehr K-H, Malerczyk V, Waldhäusl W (1996) Pharmacokinetics and pharmacodynamics of the hydroxy-metabolite of glimepiride (Amaryl) after intravenous administration. Drug Metabol Drug Interact 13:69–85

    CAS  PubMed  Google Scholar 

  28. Krentz AJ, Ferner RE, Bailey CJ (1994) Comparative tolerability profiles of oral antidiabetic agents. Drug Saf 11:223–241

    CAS  PubMed  Google Scholar 

  29. Köhler GI, Bode-Böger SM, Busse R, Hoopmann M, Welte T, Böger RH (2000) Drug–drug interactions in elderly patients: relation to hospital admissions and multiple drug use. Int J Clin Pharmacol Ther 38:504–513

    PubMed  Google Scholar 

  30. Kirchheiner J, Brockmöller J, Meineke I, Bauer S, Rohde W, Meisel C, Roots I (2002) Impact of CYP2C9 amino acid polymorphisms on glyburide kinetics and on the insulin and glucose response in healthy volunteers. Clin Pharmacol Ther 71:286–296

    Google Scholar 

  31. Niemi M, Brackman JT, Neuvonen M, Laitila J, Neuvonen PJ, Kivisto KT (2001) Effects of fluconazole and fluvoxamine on the pharmacokinetics and pharmacodynamics of glimepiride. Clin Pharmacol Ther 69:194–200

    Article  CAS  PubMed  Google Scholar 

  32. Niemi M, Neuvonen PJ, Kivisto KT (2001) Effects of gemfibrozil on the pharmacokinetics and pharmacodynamics of glimepiride. Clin Pharmacol Ther 70:439–445

    Google Scholar 

  33. Lindblad U, Melander A (2000) Sulphonylurea dose-response relationships: relation to clinical practice. Diabetes Obes Metab 2:25–31

    Article  CAS  PubMed  Google Scholar 

  34. Girardin E, Vial T, Pham E, Evreux JC (1992) Hypoglycemia induced by oral hypoglycemic agents. Records of the French regional pharmacovigilance centers 1985–1990. Ann Med Interne 143:11–17

    CAS  Google Scholar 

Download references

Acknowledgements

We are indebted to the following physicians and centres for their participation in the investigation: Dr. B. Beckmann, Dessau; Dr. H. Berkermann, Eschwege; Caritas-Klinik Pankow / Berlin; Dr.-Herbert-Nieper Krankenhaus Goslar; Dr. F. Eich, Saarburg; Dr. A. Flegel, Passau; Dr. B. Jacobs, Osnabrück; Klinikum Kaiserslautern; Dr. M. Klofat, Krefeld; Krankenhaus Moabit Berlin; Kreisklinik Spaichingen; Kreiskrankenhaus Schramberg; Kreiskrankenhaus Winsen; Dr. Malcharzik, Springe; Dr. D. Markwardt, Eberswalde; Medizinische Hochschule Hannover; Dr. R. Pilgrim, Berlin; Dr. A. Plaschke, Detmold; Dr. H.-J. Pleuser, Wittgenstein; Ch. Potberg, Lemgo; Dr. A. Risse, Dortmund; PD Dr. Th. Schleiffer, Wilhelmshaven; Dr. H.-U. Seume, Zeitz; PD Dr. A. Widjaja, Oldenburg.

Author information

Authors and Affiliations

  1. 1st Department of Medicine, Klinikum Lippe-Detmold, Röntgenstrasse 18, 32756 , Detmold, Germany

    A. Holstein, A. Plaschke, C. Hammer & E.-H. Egberts

Authors
  1. A. Holstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Plaschke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Hammer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E.-H. Egberts
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Holstein.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Holstein, A., Plaschke, A., Hammer, C. et al. Characteristics and time course of severe glimepiride- versus glibenclamide-induced hypoglycaemia. Eur J Clin Pharmacol 59, 91–97 (2003). https://doi.org/10.1007/s00228-003-0592-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-003-0592-4

Keywords

Search

Navigation