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 |
| Molecular Weight | 129.16 |
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 | Avoid; metformin is FDA Pregnancy Category B, but limited data in first trimester. Use only if clearly needed for type 2 diabetes. |
| 2nd trimester | Use with caution; monitor for fetal effects, though no evidence of major malformations. |
| 3rd trimester | Use with caution; may increase risk of neonatal hypoglycemia, but benefits may outweigh risks in diabetic mothers. |
Clinical note
Comprehensive clinical and safety monograph for GLUMETZA (GLUMETZA).
| Placental transfer | Metformin crosses the placenta with fetal concentrations similar to maternal concentrations. |
| Breastfeeding | Metformin is excreted in breast milk in low amounts. Limited data suggest no adverse effects on nursing infants. However, caution is advised, especially in premature or low-birth-weight infants. |
■ 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 |
Renal impairment (eGFR < 30 mL/min/1.73 m2)Acute metabolic acidosisHypersensitivity to metformin
| 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) |
| Food/Dietary |
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| Lactation Rating |
| L2 |
| 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. |
| 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. |
| Alcohol: may increase risk of lactic acidosis; limit intake. Dietary fiber: large changes in fiber intake may affect absorption; maintain consistent diet. High-fat meals: may affect absorption; take consistently with evening meal. |
| Clinical Pearls | GLUMETZA is a once-daily extended-release metformin formulation taken with the evening meal to reduce GI side effects and improve glycemic control. Contraindicated in eGFR <30 mL/min/1.73m2; hold for iodinated contrast studies. Check vitamin B12 levels annually due to risk of deficiency. Avoid in acute metabolic acidosis, including lactic acidosis. |
| Patient Advice | Take one tablet daily with the evening meal to minimize stomach upset. · Swallow whole; do not crush, chew, or split the tablet. · Monitor for symptoms of lactic acidosis (unusual tiredness, muscle pain, difficulty breathing, stomach discomfort with nausea/vomiting) and seek immediate medical attention. · Notify your healthcare provider if you become seriously ill, dehydrated, or have surgery or imaging with contrast dye. · Regular blood glucose monitoring and HbA1c testing are required. · You may need periodic vitamin B12 level checks. |