Summary
In the largest series of patients with glibenclamide-associated hypoglycaemia reported so far, 51 cases reported to the Swedish Adverse Drug Reactions Advisory Committee and six additional cases are reviewed and related to sales and prescription data of glibenclamide. Median age of the patients with hypoglycaemia was 75 years and 21% were 85 years or above. For comparison, the median age of a random sample (1 in 288 of all patients prescribed glibenclamide) was 70 years and only 5% were 85 years or older. In eight out of 40 cases where duration of glibenclamide treatment was recorded, the hypoglycaemic event occurred during the first month of treatment. The median daily dose of glibenclamide prescribed was 10 mg both in the hypoglycaemic cases and in the prescription sample. Coma or disturbed consciousness was the most common clinical presentation in this series and the minimum blood glucose value was 1.3 mmol/l (median). Twenty-two patients responded immediately to treatment, 24 had protracted hypoglycaemia of 12–72 h duration and 10 died. Fatal outcome was observed even with small doses of glibenclamide (2.5–5 mg/day). Previous strokes and cardiac disorders were isolated as two independent determinants of a serious course of the hypoglycaemia. Other contributing factors included impaired renal function, low food intake, diarrhoea, alcohol intake and interaction with other drugs. Thus, it is not uncommon for glibenclamide, like the first-generation sulphonylureas, to cause serious, protracted and even fatal hypoglycaemic events.
Article PDF
Similar content being viewed by others
References
Shen S-W, Bressler R (1979) Clinical pharmacology of oral antidiabetic agents. N Engl J Med 296: 493–497 and 787–793
Seltzer HS (1972) Drug-induced hypoglycemia. A review based on 473 cases. Diabetes 21: 955–966
Balant L, Fabre J, Zahnd GR (1975) Comparison of the pharmacokinetics of glipizide and glibenclamide in man. Eur J Clin Pharmacol 8: 63–69
Sartor G, Melander A, Scherstén B, Wåhlin-Boll E (1980) Comparative single-dose kinetics and effects of four sulfonylureas in healthy volunteers. Acta Med Scand 208: 301–307
National Corporation of Swedish Pharmacies (1975–1980) Statistical reports of drug sales and prescriptions (annual publications). Läkemedelsstatistik AB, Stockholm
Lunde PKM, Baksaas I, Halse M, Halvorsen T, Strømnes B, Öyd vin K (1978) Methodology in drug utilization studies. The need for a uniform drug classification and a comparable unit of measurements. In: Bergman U, Grimsson A, Wahba AHW, Westerholm B (eds). Drug utilization studies — Methods and applications, European Series No.8. WHO Regional Publications, Copenhagen pp 17–28
Kristoferson K, Wessling A (1977) Tre års receptundersökningar. Svensk Farmaceutisk Tidskrift 81: 309–316
Böttiger LE, Westerholm B (1973) Drug-induced blood dyscrasias in Sweden. Br Med J 3: 339–342
Arneborn P, Palmblad J (1978) Drug-induced neutropenia in the Stockholm region 1973–75: Frequency and causes. Acta Med Scand 204: 283–286
Seltzer HS (1979) Severe drug-induced hypoglycemia: a review. Compr Therapy 5: 21–29
Hasslacher C, Wahl P (1971) Häufigkeit und Schwere therapiebedingter Hypoglykämien bei Diabetikern. Deutsch Med Wochenschr 96: 1787–1791
Raymond JP, Chimènes H, Klotz HP (1971) Les dangers d'hypoglycémies sévères au Glibenclamide (Daonil ou Euglucan). A propos de 10 comas survenus en 6 mois. Diabète 19: 31–32
Codaccioni J-L, Rubin P, Mattel A, Vague P (1971) Quatre hypoglycémies graves dont une mortelle au cours du traitement par Glibenclamides. Diabète 19: 37–41
Frerichs H, Deuticke U, Creutzfeldt W (1973) Nebenwirkungen der oralen Antidiabetika: Hypoglykämie. Med Klin 68: 363–370
De Vigan C, Delporte MP, Thomas M, Perrault M (1976) Les accidents hypoglycémiques des thérapeutiques orales du diabète. Nouv Presse Med 5: 906–910
Clarke BF, Campbell IW (1975) Long-term comparative trial of glibenclamide and chlorpropamide in diet-failed, maturity-onset diabetics. Lancet 1: 246–248
Gutsche H, Höpker W, Boenicke G (1969) Ursachen und Verhütung von Hypoglykämien unter Glibenclamide. Med Welt 20: 1876–1880
Gottesbüren H, Gerdes H, Littman KP (1970) Schwere Hypoglykämien nach Glibenclamide. Verh Dtsch Ges Inn Med 76: 433–435
Nistrup Madsen S, Persson I (1970) Behandling med et nyt antidiabetikum: glybenklamid. (Treatment with a new antidiabetic, Glybenclamide). Ugeskr Laeger 132: 143–147
Carlström S, Monti M (1973) Hypoglykämi vid behandling av diabetes med glibenklamid (Hypoglycemia in the treatment of diabetes with glibenclamide). Läkartidningen 70: 1020–1022
Hildick-Smith M (1974) Epilepsy in the elderly. Age Ageing 3: 203–208
Cuartero AR, Medina JV (1976) Coma hipoglucémico por antidiabéticos orales. Rev Clin Esp 140: 579–583
Ahmed A (1976) Hypoglycaemic coma with Daonil. Indian J Med Sci 30: 140
Talseth T, Eika C (1978) Langvarig glibenklamid-indusert hypoglykemi. Tidskr Nor Laegeforen 98: 949–950
Kalimo H, Olsson Y (1980) Effects of severe hypoglycemia on the human brain. Neuropathological case reports. Acta Neurol Scand 62: 345–356
Asplund K, Lithner F (1979) Svår hypoglykämi utlöst av glibenklamid (Severe hypoglycaemia induced by glibenclamide). Läkartidningen 76: 967–968
Balant L, Zahnd GR, Weber F, Fabrie J (1977) Behaviour of glibenclamide on repeated administration to diabetic patients. Euro J Clin Pharmacol 11: 19–25
Sartor G, Melander A, Schemen B, Wåhlin-Boll E (1980) Serum glibenclamide in diabetic patients, and influence of food on the kinetics and effects of glibenclamide. Diabetologia 18: 17–22
Melander A, Sartor G, Wåhlin E, Scherstén B, Bitzén P-O (1978) Serum tolbutamide and chlorpropamide concentrations in patients with diabetes mellitus. Br Med J 1: 142–144
Bergman U, Christenson I, Jansson B, Wiholm B-E, Östman J (1980) Wide variations in serum chlorpropamide concentrations among out-patients. Eur J Clin Pharmacol 18: 165–169
Eichelbaum M (1982) Defective oxidation of drugs: Kinetic and therapeutic implications. Clin Pharmacokin 7: 1–22
Berger W (1974) Hypoglykämien unter der Behandlung mit Sulfonylharnstoffen. In: Belser FG, Froesch ER (eds) Diabetische Enteropathie — Hypoglykämien. Hans Huber, Bern Stuttgart Wien, pp 48–65
Balant L, Fabre J, Loutan L, Samini H (1979) Does 4-transhydroxy-glibenclamide show hypoglycemic activity? Arzneim Forsch 29: 162–163
O'Brien JP, Sharpe AR (1967) The influence of renal disease on the insulin 1–131 disappearance curve in man. Metabolism 16: 76–83
Lowrie EG, Soeldner JS, Hampers CL, Merril JP (1970) Glucose metabolism and insulin secretion in uremie, prediabetic and normal subjects. J Lab Clin Med 76: 603–615
Hansen JM, Christensen LK (1977) Drug interactions with oral sulphonylurea drugs. Drugs 13: 24–34
Blass JP, Gibson GE (1978) Cholinergic systems and disorders of carbohydrate catabolism. Adv Behav Biol 24: 791–803
Gibson GE, Blass JP (1976) Impaired synthesis of acetylcholine in brain accompanying mild hypoxia and hypoglycemia. J Neurochem 27: 37–42
Coelingh Bennink HJT, Schreurs WHP (1975) Improvement of oral glucose tolerance in gestational diabetes by pyridoxine. Br Med J 3: 13–15
Jenkins DJA, Leeds AR, Gassull MA, Wolever IMS, Goff DV, Alberti KG, Hockaday TDR (1976) Unabsorbable carbohydrates and diabetes: Decreased post-prandial hyperglycaemia. Lancet 2: 172–174
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Asplund, K., Wiholm, BE. & Lithner, F. Glibenclamide-associated hypoglycaemia: A report on 57 cases. Diabetologia 24, 412–417 (1983). https://doi.org/10.1007/BF00257338
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00257338