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

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 +/- 19.6 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.