GLUMETZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GLUMETZA (GLUMETZA).
Metformin hydrochloride, a biguanide, improves glucose tolerance in type 2 diabetes mellitus by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and improving insulin sensitivity (increasing peripheral glucose uptake and utilization).
| Metabolism | Metformin is not metabolized; excreted unchanged in urine via renal tubular secretion. No hepatic metabolism or CYP450 involvement. |
| Excretion | Renal (90% as unchanged drug); fecal (minor, <5%) |
| Half-life | 6.2 hours (terminal) in healthy adults; prolonged in renal impairment (e.g., 18 hours in CrCl <30 mL/min) |
| Protein binding | Negligible (<5%); not significantly bound to plasma proteins |
| Volume of Distribution | 654 ± 358 L (approximately 9.3 L/kg for a 70 kg individual) indicating extensive tissue distribution |
| Bioavailability | 55–60% for extended-release tablets (GLUMETZA); 50–60% for immediate-release metformin |
| Onset of Action | Oral (extended-release): 2–4 hours for reduction in hepatic glucose output; peak effect at 6–8 weeks |
| Duration of Action | 24 hours (once-daily dosing) with sustained glycemic control; clinical effect persists for 1–2 days after discontinuation |
Initial: 500 mg orally once daily with evening meal; increase by 500 mg weekly based on tolerability. Maximum: 2000 mg once daily with evening meal. Extended-release formulation.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | eGFR 30-45 mL/min: maximum 1000 mg/day. eGFR <30 mL/min: contraindicated. Do not initiate if eGFR <45 mL/min. Monitor renal function annually. |
| Liver impairment | No specific guidelines for Child-Pugh; contraindicated in severe hepatic impairment. Use caution in mild-to-moderate impairment due to increased risk of lactic acidosis. |
| Pediatric use | Not approved for pediatric patients <18 years; safety and efficacy not established. |
| Geriatric use | Start at low dose (500 mg once daily); titrate slowly. Monitor renal function closely due to age-related decline. Avoid in eGFR <45 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GLUMETZA (GLUMETZA).
| Breastfeeding | Metformin is excreted into human milk with a milk-to-plasma ratio (M/P) of approximately 0.35. Breastfed infants receive about 0.5% of maternal weight-adjusted dose. Considered compatible with breastfeeding, especially if the infant is healthy and full-term. Monitor infant for signs of hypoglycemia and gastrointestinal effects. |
| Teratogenic Risk | Pregnancy Category B. No evidence of teratogenicity in animal studies. Limited human data; risk cannot be excluded. Insulin is preferred for gestational diabetes. Metformin may be associated with increased risk of preeclampsia and perinatal mortality in women with polycystic ovary syndrome, but data are conflicting. First trimester: no known major malformations. Second and third trimesters: limited data; use only if clearly needed. |
■ FDA Black Box Warning
Lactic acidosis: Rare but serious, fatal in 50% of cases. Risk increases with acute renal impairment, sepsis, dehydration, excessive alcohol intake, hepatic impairment, and use of IV iodinated contrast media. Discontinue metformin immediately if lactic acidosis is suspected.
| Serious Effects |
["Severe renal impairment (eGFR <30 mL/min/1.73 m²)","Acute or chronic metabolic acidosis (including diabetic ketoacidosis)","History of lactic acidosis with metformin","Hypersensitivity to metformin hydrochloride","Acute conditions that may alter renal function (e.g., dehydration, severe infection, shock)"]
| Precautions | ["Lactic acidosis (see black box warning)","Renal impairment: Monitor renal function; contraindicated if eGFR <30 mL/min/1.73 m²; not recommended if eGFR 30-45 mL/min/1.73 m² and initiating therapy","Cardiovascular collapse (e.g., from acute myocardial infarction, shock)","Hypoglycemia: Risk increased with caloric restriction, strenuous exercise, alcohol, or concomitant use of sulfonylureas/insulin","Vitamin B12 deficiency: Decreased absorption; monitor levels periodically","Acute alcohol intoxication: May increase risk of lactic acidosis","Surgery and radiographic studies: Temporarily discontinue metformin before procedures with restricted food/fluid intake or before IV iodinated contrast media (hold for 48 hours post-procedure and resume if renal function normal)"] |
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| Fetal Monitoring | Monitor maternal renal function and blood glucose levels closely. Assess fetal growth and well-being via ultrasound and nonstress testing in late pregnancy given potential for increased adverse outcomes. Monitor for signs of preeclampsia and gestational hypertension. |
| Fertility Effects | Metformin may improve ovulatory function and fertility in women with polycystic ovary syndrome (PCOS) by reducing insulin resistance and hyperinsulinemia. Weight loss and resumption of ovulation can occur. No known adverse effects on male fertility. |