Sulfonylurea Prescribing

Sulphonylureas close pancreatic beta cell potassium channels and stimulate insulin secretion regardless of glucose, so they lower HbA1c effectively and cheaply but cause hypoglycaemia and weight gain. They are used where cost or supply limits other drugs, or as a second or third agent.

Short-acting agents are safer. Gliclazide, glimepiride and glipizide cause less severe hypoglycaemia than glibenclamide, which has active metabolites and long action.

Beta cell failure. Benefit fades as beta cell function declines.

Preferred. Gliclazide or glimepiride. Glipizide is an alternative where available.

Avoid. Glibenclamide in patients over 65 years, in chronic kidney disease, and in decompensated liver disease.

Contraindications. Type 1 diabetes, diabetic ketoacidosis, pregnancy, severe hepatic or renal impairment for most agents, and hypersensitivity to sulphonamide-type compounds in some patients.

G6PD deficiency. Sulphonylureas can cause haemolysis in G6PD deficiency. Test or use another agent where deficiency is possible.

Gliclazide. 40 to 80 mg orally once daily with breakfast, titrated every 2 to 4 weeks; immediate-release maximum 320 mg daily in 2 divided doses. Modified-release 30 mg once daily, increased to a maximum of 120 mg daily.

Glimepiride. 1 mg orally once daily with breakfast, increased every 1 to 2 weeks by 1 mg; usual maximum 6 mg daily (8 mg in some labels).

Glipizide. 2.5 to 5 mg orally once daily before breakfast, increased to a maximum of 20 mg for a single dose and 40 mg daily in divided doses.

Glibenclamide (where unavoidable). 2.5 mg orally once daily with breakfast, maximum 15 mg daily; not advised in the elderly or in kidney impairment.

Kidney function. Gliclazide and glimepiride may be used with caution to eGFR 30 with dose reduction; avoid under eGFR 30 if alternatives exist. Reduce the dose by 50% in older adults with reduced intake.

Combination with insulin. When starting basal insulin, reduce the sulphonylurea dose by 50% or stop it if hypoglycaemia occurs.

Interactions. Hypoglycaemia risk rises with co-trimoxazole, fluconazole, clarithromycin, fluoroquinolones, warfarin, and beta blockers that mask warning symptoms.

Special groups. - Liver disease: avoid glibenclamide; gliclazide only at low dose in compensated disease. - Pregnancy: stop before conception; insulin is used. - Breastfeeding: avoid long-acting agents. - Older adults: use the lowest dose, and consider stopping when HbA1c is under 58 mmol/mol (7.5%). - Fasting during Ramadan: review the regimen with the patient before the month begins, prefer gliclazide or glimepiride, and take the main dose with the evening meal.

Monitoring. Capillary glucose when starting, changing dose, or if symptoms occur. HbA1c every 3 months. Teach hypoglycaemia recognition and treatment.

Hypoglycaemia treatment. Give 15 to 20 g of fast-acting carbohydrate if the patient is conscious, repeat after 15 minutes if glucose remains under 4 mmol/L, then give a longer-acting snack. If unconscious, give glucagon 1 mg intramuscularly or 20% glucose 75 to 100 mL intravenously. Sulphonylurea hypoglycaemia can recur for 24 to 72 hours.

Stopping. Stop for severe hypoglycaemia, falling eGFR, or poor intake.

Referral and escalation. Admit for severe or recurrent hypoglycaemia on long-acting agents, or after overdose.