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Glibenclamide

AEMPS

Oral hypoglycemic agents. Sulfonylureas

ATC code: A10BB01

Brand names: Glynase, DiaBeta, Micronase

Updated · Methodology

Indications

A

Neonatal diabetes (monogenic forms)

First line

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.

Sources

  1. Pediatr Diabetes: ISPAD Clinical Practice Consensus Guidelines 2022: The diagnosis and management of monogenic diabetes in children and adolescents. (2022)
  2. ADA: Standards of Care in Diabetes 2024 – pharmacologic approaches to glycemic treatment (2024)
  3. N Engl J Med: Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. (2006)
  4. Lancet Diabetes Endocrinol: Effectiveness and safety of long-term treatment with sulfonylureas in patients with neonatal diabetes due to KCNJ11 mutations: an international cohort study. (2018)
  5. Diabetes Care: 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes—2024 (2023)

ICD-10: P70.2 · ICD-11: KB60.2

B

Type 2 diabetes mellitus

Second line

Glibenclamide is a long-experienced sulfonylurea oral hypoglycemic agent. Reduces by 1.0–1.5% as monotherapy. 2024 and ADA/ 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.

Sources

  1. ADA: Standards of Care in Diabetes 2024 – pharmacologic approaches to glycemic treatment (2024)
  2. ADA/EASD: Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association and the European Association for the Study of Diabetes (2022)
  3. Минздрав РФ: Сахарный диабет 2 типа у взрослых. Клинические рекомендации (ID 290) (2022)
  4. ГРЛС: Глибенкламид – Государственный реестр лекарственных средств (2024)

ICD-10: E11 · ICD-11: 5A11

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

F

Gestational diabetes mellitus

Not recommended

Glibenclamide is not first-line for gestational diabetes. 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.

Sources

  1. ADA: Standards of Care in Diabetes 2024 – pharmacologic approaches to glycemic treatment (2024)

ICD-10: O24.4 · ICD-11: JA63.2

F

Type 2 diabetes in elderly patients

Not recommended

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.

Sources

  1. AGS: American Geriatrics Society 2023 Updated AGS Beers Criteria (2023)
  2. ADA: Standards of Care in Diabetes 2024 – pharmacologic approaches to glycemic treatment (2024)

ICD-10: E11 · ICD-11: 5A11

How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

Stimulates insulin secretion by pancreatic beta cells via blockade of membrane ATP-sensitive potassium channels. This causes cell depolarization, calcium influx and exocytosis of insulin granules. The effect is glucose-independent and increases hypoglycemia risk. A long-acting drug with active metabolites that accumulate in renal impairment.

Safety

Contraindications

  • Type 1 diabetes
  • Diabetic ketoacidosis, precoma, coma
  • Severe renal impairment (eGFR < 30 mL/min/1.73 m²)
  • Severe hepatic impairment
  • Pregnancy, lactation
  • Glucose-6-phosphate dehydrogenase deficiency
  • Hypersensitivity to sulfonylureas and sulfonamides

Serious adverse effects

  • Severe prolonged hypoglycemia with coma and neurological sequelae
  • Hemolytic anemia in G6PD deficiency
  • Hyponatremia, SIADH
  • Severe cutaneous reactions (Stevens-Johnson syndrome)

Common adverse effects

  • Hypoglycemia
  • Weight gain of 2–4 kg in the first months of therapy
  • Nausea, dyspepsia
  • Rash, pruritus

Uncommon adverse effects

  • Leukopenia, thrombocytopenia
  • Cholestatic jaundice
  • Photosensitivity

Pregnancy: can you take Glibenclamide?

AEMPS summary of product characteristics (section 4.6): glibenclamide should not be taken during pregnancy. Patients switch to insulin for the duration of pregnancy, and those planning a pregnancy switch to insulin beforehand.

Breastfeeding: can you take Glibenclamide?

Passes into breast milk in small amounts, but a risk of neonatal hypoglycemia exists. Not used during breastfeeding; replaced with insulin or metformin.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

Taken 15–30 minutes before breakfast. Doses above 5 mg daily are split between breakfast and dinner. Skipping a meal after dosing causes hypoglycemia.

Monitoring

is checked every 3 months until target is met, then every 6 months. Self-monitoring of blood glucose is mandatory, especially with changes in exercise, diet or intercurrent illness. eGFR is assessed at least annually. With declining renal function, switch to an agent less dependent on renal excretion (gliclazide MR) or to a different class.

Special situations

The patient is taught to recognize hypoglycemia symptoms (sweating, tremor, hunger, palpitations, confusion) and to treat them with fast carbohydrates. In severe hypoglycemia – injectable glucagon and emergency medical care. On glibenclamide, hypoglycemia may be prolonged and recurrent, requiring multi-hour observation and glucose infusion.

Drug interactions

Enhance effect and hypoglycemia risk: beta blockers (mask symptoms), ACE inhibitors, fibrates, fluconazole, co-trimoxazole, warfarin. Reduce effect: glucocorticoids, thiazide diuretics, thyroid hormones, sympathomimetics. Alcohol increases hypoglycemia risk and may produce a disulfiram-like reaction.

Common myths

Myth: «glibenclamide is the most effective glucose-lowering drug because it has been used the longest». Fact: efficacy is comparable to other sulfonylureas and metformin, but risk and tolerability are worse.

Myth: «if you skip a meal, just skip the pill». Fact: glibenclamide is long-acting; skipping a meal after a morning dose carries hypoglycemia risk at 12–14 h.

Myth: «if it does not work, just increase the dose». Fact: with inadequate response, add a different class (metformin, SGLT2 inhibitors). Escalating sulfonylurea dose gives little benefit but increases hypoglycemia risk.

Drug–drug interactions

6 pairs found. Sorted from critical to minor.

MajorCiprofloxacinFluoroquinolone antibacterials

Mechanism

Ciprofloxacin disrupts insulin secretion from pancreatic β-cells and concurrently inhibits CYP2C9 – the glibenclamide metabolic route. Glibenclamide plasma levels rise, intensifying its hypoglycaemic effect. warning was issued in 2018.

Symptoms

Severe hypoglycaemia: sweating, tremor, hunger, tachycardia, confusion; severe cases progress to seizures and coma. Symptoms appear within 1–7 days, especially in older patients and chronic kidney disease.

Management

Avoid the combination. Alternative antibiotics: a cephalosporin or fosfomycin (no CYP2C9 effect and no β-cell impact). If ciprofloxacin is needed, monitor glucose 4 times daily and warn the patient about hypoglycaemia signs.

Sources

Pair details →Ciprofloxacin →

MajorFluconazoleAntifungals, triazole derivatives

Mechanism

Fluconazole at 200 mg/day or above blocks CYP2C9 – the main glibenclamide metabolic route. Glibenclamide plasma levels rise 2- to 3-fold; hypoglycaemic effect intensifies.

Symptoms

Severe hypoglycaemia: sweating, tremor, hunger, tachycardia, confusion; severe cases progress to seizures and coma. Symptoms appear within 1–7 days, especially in older patients and chronic kidney disease.

Management

For short fluconazole courses, monitor glucose 4 times daily; if needed, halve glibenclamide. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses.

Sources

Pair details →Fluconazole →

ModerateAcetylsalicylic acidAntiplatelet agents (low dose) / NSAIDs (analgesic dose)

Mechanism

High aspirin doses displace glibenclamide from albumin binding and suppress hepatic gluconeogenesis. Hypoglycaemia risk at aspirin doses above 3 g/day.

Symptoms

Sweating, tremor, hunger, tachycardia, confusion. Severe cases: seizures and coma. Symptoms appear 1–2 days after starting high aspirin doses.

Management

Cardioprotective aspirin doses (75–100 mg) are acceptable without adjustment. At high doses, monitor glucose 4 times daily in the first week; reduce glibenclamide if needed.

Sources

Pair details →Acetylsalicylic acid →

ModerateAmitriptylineTricyclic antidepressants (TCA)

Mechanism

TCAs may mask hypoglycaemia symptoms (tremor, tachycardia) via anticholinergic effect. No direct pharmacokinetic interaction.

Symptoms

Sudden confusion, weakness, ataxia without preceding tachycardia or sweating. Older patients: risk of severe hypoglycaemia without warning symptoms.

Management

Warn the patient that the TCA masks hypoglycaemia warning signs. Check glucose more often (4 times daily in the first week, then by self-monitoring). In older patients, prefer gliclazide (less hypoglycaemia) or metformin/DPP-4 inhibitor over glibenclamide.

Sources

Pair details →Amitriptyline →

ModerateBisoprololSelective beta-adrenergic blockers

Mechanism

Beta-blockers can mask the adrenergic warning signs of hypoglycaemia: fast pulse, palpitations, sweating (bisoprolol and glibenclamide SmPCs). The bisoprolol SmPC warns that with sulfonylureas, glibenclamide among them, the risk of severe hypoglycaemia may rise. Glibenclamide is long-acting and so causes severe hypoglycaemia more often than short-acting sulfonylureas, and in older people hypoglycaemia is harder to recognise (glibenclamide SmPC).

Symptoms

Sudden confusion, weakness, ataxia without preceding tachycardia or sweating. Older patients: risk of severe hypoglycaemia without warning symptoms.

Management

The combination can be used with caution (bisoprolol SmPC). Advise the patient with diabetes to monitor blood glucose carefully (bisoprolol SmPC) and explain in advance that on a beta-blocker the fast pulse, palpitations and sweating of hypoglycaemia may weaken or disappear (bisoprolol and glibenclamide SmPCs). In older people the starting and maintenance glibenclamide doses are chosen conservatively, because hypoglycaemia is more frequent and harder to notice. The patient always carries at least 20 g of glucose or sugar to treat hypoglycaemia at once (glibenclamide SmPC). The US Food and Drug Administration () also requires warning patients on oral antidiabetic drugs that bisoprolol may mask signs of hypoglycaemia, particularly a fast pulse (bisoprolol FDA label).

Sources

Pair details →Bisoprolol →

ModeratePropranololNon-selective beta blocker

Mechanism

Beta-blockers mask adrenergic hypoglycaemia symptoms (tachycardia, tremor), leaving only sweating. Severe unrecognised hypoglycaemia risk rises in sulfonylurea-treated patients, especially older patients.

Symptoms

Sweating, confusion, vision changes, loss of contact. Adrenergic symptoms (tachycardia, tremor) are suppressed — the patient misses the hypoglycaemia.

Management

Do not prescribe propranolol in diabetes. Alternatives: cardioselective beta-blockers (metoprolol, bisoprolol, nebivolol) — minimally mask hypoglycaemia. Replace glibenclamide with modern glucose-lowering agents with lower hypoglycaemia risk: gliclazide MR, metformin, SGLT-2 inhibitors (dapagliflozin, empagliflozin), GLP-1 agonists (semaglutide, liraglutide). If the combination is unavoidable, teach the patient to recognise hypoglycaemia via sweating.

Sources

Pair details →Propranolol →

Label mentions18 mentions

Verbatim lines from the interaction sections, in the language of the label

From other drugs’ labels

  • MajorFluconazole
    «Sulfonilureas: Se ha demostrado que fluconazol prolonga la semivida sérica de las sulfonilureas orales (p.ej., clorpropamida, glibenclamida, glipizida y tolbutamida), cuando se administran de forma…»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateCiprofloxacin
    «Disglucemia: Al igual que con otras quinolonas, se han notificado alteraciones de la glucosa en sangre, incluyendo hipoglucemia e hiperglucemia (ver sección 4.8), generalmente en pacientes diabéticos…»

    AEMPS, section 4.4 · Open on CIMA

  • ModerateLevothyroxine sodium
    «Antidiabéticos: Levotiroxina puede reducir la eficacia hipoglicemiante de los antidiabéticos (tales como metformina, glimepirida, glibenclamida así como insulina) . Por tanto, en los pacientes…»

    AEMPS, section 4.5 · Open on CIMA

  • Candesartan
    «hidroclorotiazida, warfarina, digoxina, anticonceptivos orales, (etinilestradiol/levonorgestrel), glibenclamida, nifedipino y enalapril. No se han identificado interacciones farmacocinéticas…»

    AEMPS, section 4.5 · Open on CIMA

  • Celecoxib
    «Glibenclamida/tolbutamida: Celecoxib no afecta la farmacocinética de tolbutamida (sustrato del CYP2C9), o de g libenclamida de forma clínicamente relevante.»

    AEMPS, section 4.5 · Open on CIMA

  • Finasteride
    «No se han identificado interacciones de fármacos con importancia clínica. Finasterida presenta un metabolismo de primer paso, pero no afecta al sistema enzimático del metabolismo de fármacos ligados…»

    AEMPS, section 4.5 · Open on CIMA

  • Fluvastatin
    «Agentes antidiabéticos orales: En los pacientes que reciben sulfonilureas por vía oral (glibenclamida [gliburida], tolbutamida) para el tratamiento de la diabetes mellitus no insulinodependiente…»

    AEMPS, section 4.5 · Open on CIMA

  • Levofloxacin
    «Otra información relevante: Estudios de farmacología clínica han demostrado que la farmacocinética de levofloxacino no se vió afectada en ningún grado clínicamente relevante cuando se administraba…»

    AEMPS, section 4.5 · Open on CIMA

  • Lornoxicam
    «Sulfonilureas: (ej. glibenclamida) mayor riesgo de hipoglucemia.»

    AEMPS, section 4.5 · Open on CIMA

  • Moxifloxacin
    «Interacciones con otros medicamentos: En estudios con voluntarios diabéticos, la administración concomitante de moxifloxacino oral con glibenclamida resultó en una disminución de aproximadamente un…»

    AEMPS, section 4.5 · Open on CIMA

  • Pantoprazole
    «Otros estudios de interacciones: Los estudios de interacción con medicamentos que se metabolizan igualmente mediante estas rutas metabólicas, como carbamazepina, diazepam, glibenclamida, nifedipino y…»

    AEMPS, section 4.5 · Open on CIMA

  • Sertraline
    «Medicamentos metabolizados por el citocromo P450: Sertralina no actúa como inhibidor del CYP 3A4, CYP 2C9, CYP 2C19, y CYP 1A2 de manera clínicamente significativa. Este hecho se ha confirmado en…»

    AEMPS, section 4.5 · Open on CIMA

  • Sirolimus
    «No se han observado interacciones farmacocinéticas clínicamente significativas entre sirolimus y ninguna de las siguientes sustancias: aciclovir, atorvastatina, digoxina, glibenclamida…»

    AEMPS, section 4.5 · Open on CIMA

  • Tamsulosin
    «In vitro , la fracción libre de tamsulosina en plasma humano, no se ve modificada por diazepam, propranolol, triclormetiazida, clormadinona, amitriptilina, diclofenaco, glibenclamida, simvastatina ni…»

    AEMPS, section 4.5 · Open on CIMA

  • Topiramate
    «Glibenclamida: En un estudio de interacción fármaco-fármaco realizado en pacientes con diabetes tipo 2 se evaluó la farmacocinética en estado estacionario de glibenclamida (5 mg/día) sola y…»

    AEMPS, section 4.5 · Open on CIMA

  • Torasemide
    «Torasemida no afecta a la unión proteica de la glibenclamida ni de la warfarina ni al efecto anticoagulante de la fenprocumona (derivado cumarínico próximo) como tampoco a la farmacocinética de la…»

    AEMPS, section 4.5 · Open on CIMA

  • Valsartan
    «En estudios de interacción farmacológica con valsartán, no se han hallado interacciones clínicamente significativas entre valsartán y cualquiera de las siguientes sustancias : cimetidina, warfarina…»

    AEMPS, section 4.5 · Open on CIMA

  • Vardenafil
    «Estudios in vivo: La farmacocinética de vardenafilo (20 mg) no se vio afectada por la administración conjunta con el antagonista H 2 , ranitidina (150 mg dos veces al día), digoxina, warfarina…»

    AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Glibenclamide used for?

Glibenclamide is evaluated for the following indications with varying evidence strength: Neonatal diabetes (monogenic forms) (evidence tier A), Type 2 diabetes mellitus (evidence tier B), Gestational diabetes mellitus (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Glibenclamide?

Common side effects of Glibenclamide (≥ 1 in 100): Hypoglycemia, Weight gain of 2–4 kg in the first months of therapy, Nausea, dyspepsia, Rash, pruritus. See the Safety section for uncommon and serious reactions.

Is Glibenclamide safe during pregnancy?

AEMPS summary of product characteristics (section 4.6): glibenclamide should not be taken during pregnancy. Patients switch to insulin for the duration of pregnancy, and those planning a pregnancy switch to insulin beforehand.

Is Glibenclamide compatible with breastfeeding?

Passes into breast milk in small amounts, but a risk of neonatal hypoglycemia exists. Not used during breastfeeding; replaced with insulin or metformin.

Can you drink alcohol while taking Glibenclamide?

Alcohol increases hypoglycemia risk and may produce a disulfiram-like reaction.

Who should not take Glibenclamide?

Glibenclamide is contraindicated in: Type 1 diabetes; Diabetic ketoacidosis, precoma, coma; Severe renal impairment (eGFR < 30 mL/min/1.73 m²); Severe hepatic impairment; Pregnancy, lactation. Full list in the Safety section.

glibenclamide is the most effective glucose-lowering drug because it has been used the longest

HbA1c efficacy is comparable to other sulfonylureas and metformin, but risk and tolerability are worse.

if you skip a meal, just skip the pill

glibenclamide is long-acting; skipping a meal after a morning dose carries hypoglycemia risk at 12–14 h.

if it does not work, just increase the dose

with inadequate response, add a different class (metformin, SGLT2 inhibitors). Escalating sulfonylurea dose gives little benefit but increases hypoglycemia risk.

Official sources

Direct links to regulator labels. Open in a new tab.

Other drugs in this group

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