GLYBURIDE AND METFORMIN HYDROCHLORIDE
Clinical safety rating: safe
Alcohol and contrast dye can increase risk of lactic acidosis Can cause lactic acidosis a rare but serious metabolic complication.
Glyburide stimulates insulin secretion from pancreatic beta cells by blocking ATP-sensitive potassium channels, leading to membrane depolarization and calcium influx. Metformin decreases hepatic glucose production, reduces intestinal glucose absorption, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
| Metabolism | Glyburide is extensively metabolized in the liver, primarily via CYP2C9, to hydroxylated metabolites. Metformin is not metabolized; it is excreted unchanged in urine. |
| Excretion | Glyburide: ~50% renal, ~50% biliary/fecal. Metformin: 90% renal unchanged, 10% fecal. |
| Half-life | Glyburide: 10 hours (range 7–20 h); Metformin: 6.2 hours (range 4–9 h). Combined effect supports twice-daily dosing. |
| Protein binding | Glyburide: >99% bound to albumin. Metformin: negligible (<5% bound). |
| Volume of Distribution | Glyburide: 0.3 L/kg; Metformin: 1–5 L/kg (large distribution into tissues). |
| Bioavailability | Glyburide: ~100% oral; Metformin: 50–60% oral, food decreases absorption slightly. |
| Onset of Action | Oral: Glyburide onset 30–60 min; Metformin onset 2–3 hours. Clinical effect on glucose seen within 1–2 weeks. |
| Duration of Action | Glyburide: 16–24 hours; Metformin: 8–12 hours. Combination duration supports BID dosing. |
Initial: 1.25 mg glyburide/250 mg metformin once daily with meals; titrate up to maximum 20 mg glyburide/2000 mg metformin per day in divided doses.
| Dosage form | TABLET |
| Renal impairment | eGFR ≥60 mL/min: no adjustment; eGFR 45-59 mL/min: reduce dose or consider discontinuation; eGFR <45 mL/min: contraindicated. |
| Liver impairment | Contraindicated in hepatic impairment (Child-Pugh class B or C); use with caution in mild hepatic impairment; consider alternative therapy. |
| Pediatric use | Not recommended for pediatric patients under 18 years due to lack of safety and efficacy data. |
| Geriatric use | Start with lowest dose (1.25 mg/250 mg once daily); avoid use if age >80 years unless normal renal function confirmed; monitor renal function closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Alcohol and contrast dye can increase risk of lactic acidosis Can cause lactic acidosis a rare but serious metabolic complication.
| FDA category | Human |
| Breastfeeding | Glyburide: Excretion into breast milk is low; M/P ratio 0.02-0.15, infant dose <0.5% maternal weight-adjusted dose. Metformin: Excreted into breast milk in low amounts; M/P ratio 0.16-0.21, infant dose <1% maternal weight-adjusted dose. Considered compatible with breastfeeding but monitor infant for hypoglycemia. |
| Teratogenic Risk |
■ FDA Black Box Warning
Lactic acidosis: Metformin accumulation can cause lactic acidosis, a rare but serious complication (mortality >50%). Risk increases with renal impairment, age, hypoxia, sepsis, or acute alcohol intoxication. Symptoms include malaise, myalgia, respiratory distress, abdominal pain, hypothermia, and altered consciousness. Prompt discontinuation and hemodialysis may be required.
| Common Effects | Diarrhea |
| Serious Effects |
["Renal impairment (eGFR <30 mL/min/1.73 m²)","Acute or chronic metabolic acidosis, including diabetic ketoacidosis","Hypersensitivity to glyburide, metformin, or any excipient","Concomitant use of bosentan (increased hepatotoxicity risk with glyburide)"]
| Precautions | ["Lactic acidosis risk: avoid in renal impairment (CrCl <30 mL/min), acute or chronic metabolic acidosis, or during intravascular iodinated contrast studies.","Hypoglycemia: glyburide component may cause severe hypoglycemia, especially in elderly, debilitated, or malnourished patients.","Cardiovascular risk: sulfonylureas may increase cardiovascular mortality (UKPDS warning).","Vitamin B12 deficiency: prolonged metformin use may reduce B12 levels; monitor annually.","Hepatic impairment: avoid in liver disease due to increased risk of lactic acidosis.","Acute alcohol intake: potentiates metformin effect on lactate metabolism."] |
Loading safety data…
| Glyburide: Pregnancy category B; minimal fetotoxicity noted but no clear teratogenicity. Metformin: Pregnancy category B; not associated with major malformations. First trimester: No increased risk of major birth defects. Second and third trimesters: Monitor for neonatal hypoglycemia with glyburide; metformin may reduce risk of gestational diabetes complications. |
| Fetal Monitoring | Maternal: Renal function, liver function, serum glucose, HbA1c, signs of lactic acidosis (rare). Fetal: Growth scans, amniotic fluid volume, non-stress tests, biophysical profiles in third trimester. Neonatal: Blood glucose monitoring for 24-48 hours after delivery. |
| Fertility Effects | No known negative effects on fertility in males or females. Metformin may improve ovulatory function in women with polycystic ovary syndrome (PCOS). Glyburide does not adversely affect reproduction. |