Metformin

# Metformin ## Overview - **Classification**: Biguanide, Antihyperglycemic Agent - **Mechanism**: Decreases hepatic glucose production, decreases intestinal glucose absorption, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. ## Primary Indications 1. **Type 2 Diabetes Mellitus (T2DM)** - First-line agent for glycemic control. 2. **Polycystic Ovary Syndrome (PCOS)** - Off-label use to improve insulin resistance, menstrual regularity, and ovulation. ## Adult Dosing ### Standard Dosing **Type 2 Diabetes Mellitus (T2DM)** - **Initial Dose**: **500 mg** - **Frequency**: Once or twice daily with meals (e.g., 500 mg BID or 850 mg once daily) - **Route**: Oral - **Titration**: Increase by **500 mg** weekly or **850 mg** every 2 weeks as tolerated - **Maximum Dose**: **2550 mg/day** (immediate-release) or **2000-2500 mg/day** (extended-release) **Polycystic Ovary Syndrome (PCOS)** (Off-label) - **Initial Dose**: **500 mg** - **Frequency**: Once daily with dinner - **Route**: Oral - **Titration**: Gradually increase to **500-1000 mg** twice daily - **Maximum Dose**: **2000 mg/day** ### Dose Adjustments - **Renal Impairment**: - **eGFR ≥60 mL/min/1.73 m²**: No dose adjustment needed. - **eGFR 45-59 mL/min/1.73 m²**: Max dose **1000-1700 mg/day**. Monitor eGFR every 3-6 months. - **eGFR 30-44 mL/min/1.73 m²**: Max dose **850 mg/day**. Consider reducing dose by 50%. Monitor eGFR every 3 months. - **eGFR <30 mL/min/1.73 m²**: **Contraindicated**. - **Hepatic Impairment**: Not recommended due to increased risk of lactic acidosis. - **Elderly Patients**: Use caution; monitor renal function closely. Start with lower initial doses. ## Pediatric Dosing ### Neonates (0-28 days) - **Dose**: Not indicated for T2DM. - **Special Notes**: No established role for Metformin in neonates. ### Infants (1-12 months) - **Dose**: Not indicated for T2DM. - **Special Notes**: No established role for Metformin in infants. ### Children (1-12 years) - **Indication**: Type 2 Diabetes Mellitus (ages 10-12 years) - **Initial Dose**: **500 mg** - **Frequency**: Once or twice daily with meals (e.g., 500 mg BID) - **Route**: Oral - **Titration**: Increase by **500 mg** weekly to **2000 mg/day** in divided doses - **Maximum**: **2000 mg/day** ### Adolescents (13-18 years) - **Indication**: Type 2 Diabetes Mellitus - **Initial Dose**: **500 mg** - **Frequency**: Once or twice daily with meals (e.g., 500 mg BID) - **Route**: Oral - **Titration**: Increase by **500 mg** weekly up to **2000 mg/day** in divided doses - **Maximum**: **2000 mg/day** (Extended-release max **2500 mg/day**) - **Special Notes**: Generally follows adult dosing guidelines with careful monitoring. ## Safety Information ### Contraindications - **Absolute**: Severe renal impairment (eGFR <30 mL/min/1.73 m²). - **Absolute**: Acute or chronic metabolic acidosis (including diabetic ketoacidosis), with or without coma. - **Absolute**: Hypersensitivity to metformin. - **Absolute**: Concurrent use with iodinated contrast media in patients with eGFR <60mL/min/1.73m² (temporarily discontinue). - **Relative**: Conditions associated with hypoxemia (e.g., heart failure, acute MI, severe infection). ### Common Adverse Effects - **Very Common (>10%)**: Diarrhea, Nausea/Vomiting, Flatulence, Abdominal discomfort. - **Common (1-10%)**: Headache, Dizziness, Fatigue, Lactic acidosis (rare but serious). - **Serious but Rare**: Lactic Acidosis (Black Box Warning), Vitamin B12 deficiency. ### Key Drug Interactions - **Iodinated Contrast Media**: Risk of acute renal failure and lactic acidosis. **Discontinue metformin** 48 hours prior to procedure, restart 48 hours after if renal function is stable. - **Carbonic Anhydrase Inhibitors (e.g., Topiramate, Acetazolamide)**: May increase risk of lactic acidosis. Monitor patient for symptoms. - **Cimetidine**: May increase metformin levels by reducing renal clearance. Monitor for side effects. - **Alcohol**: Potentiates metformin's effect on lactate metabolism, increasing lactic acidosis risk. Avoid excessive alcohol intake. ## Monitoring & Follow-up - **Before Treatment**: Baseline renal function (eGFR), HbA1c, Vitamin B12 (if clinically indicated). - **During Treatment**: - **HbA1c**: Every 3-6 months. - **Renal Function (eGFR)**: Annually, or more frequently if eGFR is borderline or risk factors for kidney impairment exist (e.g., CKD, elderly). - **Vitamin B12 levels**: Annually, or if symptoms of deficiency (e.g., anemia, neuropathy) develop. - **Clinical Signs**: Watch for signs of lactic acidosis (malaise, myalgia, somnolence, hyperventilation). ## Clinical Pearls - 💡 **Titration**: Start low and titrate slowly to minimize GI side effects. - 💡 **Administration**: Take with food (or immediately after) to reduce gastrointestinal upset. - 💡 **Extended-release (XR)**: Can be taken once daily with the evening meal. May improve GI tolerability. - 💡 **Vitamin B12**: Consider supplementation if deficiency is confirmed, especially with long-term use. - 💡 **Sick Day Management**: Advise patients to temporarily hold metformin during acute illness, dehydration, or before procedures requiring fasting. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.