Glibenclamide

In patients with neonatal diabetes due to activating mutations in KCNJ11 or ABCC8, glibenclamide replaces insulin and restores physiologic glycemic regulation. The mechanism: sulfonylurea closes the mutant ATP-sensitive potassium channel of the β-cell and restores glucose-responsive insulin secretion. Switching from insulin to glibenclamide in these patients is supported by international expert groups (ISPAD 2022, Diabetologia 2006 Pearson) at doses higher than standard adult dosing, up to 1–2 mg/kg daily.

Used after genetic confirmation of the mutation in a specialist endocrinology center. Dose titration and insulin tapering are performed under glycemic and C-peptide monitoring in an inpatient setting.

Glibenclamide is a long-experienced sulfonylurea oral hypoglycemic agent. Reduces HbA1c by 1.0–1.5% as monotherapy. ADA 2024 and ADA/EASD 2022 do not recommend sulfonylureas as first choice in T2D due to increased hypoglycemia risk and lack of cardiovascular benefit. Metformin, SGLT2 inhibitors and GLP-1 RAs are preferred. Glibenclamide remains on the market as a low-cost alternative when modern drugs are not accessible.

Not used at eGFR < 60 mL/min/1.73 m² due to accumulation of active metabolites and risk of prolonged hypoglycemia. Patients at hypoglycemia risk (irregular meals, advanced age, exercise without dose adjustment) should not receive glibenclamide.

Glibenclamide is not first-line for gestational diabetes. ADA 2024 and Russian clinical guidelines specify insulin as the agent of choice. Metformin is a possible alternative in selected patients after discussion with the endocrinologist and obstetrician. Glibenclamide crosses the placenta in clinically significant amounts and is associated with higher rates of neonatal hypoglycemia and fetal macrosomia versus insulin (Cochrane 2017).

If a patient with prepregnancy type 2 diabetes was on glibenclamide, switch to insulin at the planning stage or when pregnancy is confirmed.

Glibenclamide is not used in patients over 65. The 2023 Beers Criteria classify the drug as «avoid in older adults» due to high risk of prolonged hypoglycemia. Active metabolites accumulate with age-related eGFR decline, thyroid disorders and dehydration, sharply increasing severe hypoglycemia risk – a leading cause of falls and hospitalizations in older diabetic patients.