Metformin (Biguanides)

What This Medicine Does

Metformin works through three main mechanisms:

1. Reduces liver glucose production - Your liver normally makes sugar (gluconeogenesis); metformin dials this down
2. Improves insulin sensitivity - Your cells respond better to insulin you produce
3. Slows intestinal glucose absorption - Less sugar enters your bloodstream after meals

The result: Lower blood sugar without causing dangerous drops (hypoglycemia) when used alone.

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Understanding Metformin and Blood Sugar

Why Metformin is First-Line

Metformin is recommended as initial therapy for most people with type 2 diabetes because:

• Proven track record - Used since the 1950s, extensively studied
• Cardiovascular benefit - Unlike some diabetes drugs, metformin reduces heart disease risk
• Weight neutral or loss - Unlike insulin or sulfonylureas which cause weight gain
• Low hypoglycemia risk - When used alone, almost no risk of dangerously low blood sugar
• Inexpensive - Available as generic for under $20/month

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What to Expect: A Timeline

Week 1-2: Adjustment Period

• Start with low dose (500 mg once daily) to minimize side effects
• Some digestive upset is common but usually improves
• Blood sugar may start improving

Week 2-4: Dose Escalation

• Dose gradually increased to target (usually 1,000-2,000 mg daily)
• Extended-release (ER) formulation may be better tolerated
• Side effects typically decrease as your body adjusts

Month 1-3: Full Effect

• Maximum blood sugar-lowering effect achieved
• HbA1c reduction: 1-2% on average
• Weight may decrease modestly (2-5 lbs average)

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Common Things You Might Notice

Digestive Side Effects (Most Common)

What people report:

• Nausea or stomach upset
• Diarrhea or loose stools
• Gas and bloating
• Metallic taste in mouth
• Decreased appetite

Important context:

• Side effects are dose-dependent and often temporary
• 30-50% experience some digestive upset initially
• Only 5-10% need to stop because of side effects long-term

What to do:

• Take with meals (not on empty stomach)
• Start low, go slow with dose increases
• Extended-release formulation causes fewer side effects
• Side effects usually improve within 2-4 weeks

Other Common Effects

• Decreased appetite - Can help with weight loss
• Mild weight loss - Average 2-5 lbs, not dramatic
• Vitamin B12 deficiency - Can develop with long-term use

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When to Call Your Doctor

Seek Immediate Care For:

• Unusual muscle pain, weakness, or trouble breathing - Possible lactic acidosis
• Extreme fatigue, dizziness, or confusion - Could indicate serious problems
• Severe persistent vomiting or diarrhea - Can lead to dehydration

Contact Your Doctor Soon For:

• Persistent side effects that don't improve after 2-3 weeks
• Planned medical procedures with contrast dye
• Plans for excessive alcohol use
• Surgery scheduled

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Daily Practical Tips

1. Take with food - Always take metformin with a meal to reduce digestive upset

2. Be patient with side effects - Most digestive issues improve within a few weeks

3. Extended-release option - Ask about metformin ER if immediate-release causes problems

4. Don't skip doses - Consistency matters for blood sugar control

5. Limit alcohol - Heavy drinking increases lactic acidosis risk

6. Stay hydrated - Especially when sick, during exercise, or in hot weather

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Pregnancy & Breastfeeding

Metformin is increasingly used in pregnancy, especially for PCOS and gestational diabetes:

• Category B - Generally considered safe, but discuss with your doctor
• Often continued in PCOS pregnancies
• May be used for gestational diabetes when insulin isn't feasible

breastfeeding:

• Metformin passes into breast milk but in small amounts
• Generally considered compatible with breastfeeding
• Monitor infant for any effects

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Food & Medicine Interactions

Alcohol

Other Important Interactions

• Contrast dye - Used in CT scans and some procedures

  • May need to hold metformin before and after
  • Based on kidney function
  • Always tell radiology staff you're on metformin

• Certain medications can affect kidneys or increase lactic acidosis risk:

  • Some HIV medications
  • Certain diuretics
  • Some antibiotics

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For Healthcare Professionals

Clinical Information

Pharmacology & Mechanism

Metformin's primary mechanism is activation of AMP-activated protein kinase (AMPK), leading to:

• Inhibition of hepatic gluconeogenesis
• Increased insulin-mediated glucose uptake
• Decreased intestinal glucose absorption
• Modulation of gut microbiome

Dosing & Administration

Starting dose:

• 500 mg once daily with evening meal
• OR 850 mg once daily
• Increase by 500 mg weekly as tolerated

Target dose:

• 2,000 mg daily for maximum glycemic effect
• Some patients benefit from doses up to 2,550 mg daily
• Extended-release: 2,000 mg daily maximum

Special populations:

• Renal impairment: Use if eGFR ≥30 mL/min; avoid if eGFR ＜30
• Elderly: Start lower, assess renal function more frequently

Monitoring

Baseline:

• HbA1c
• Serum creatinine/eGFR
• Vitamin B12 level
• Liver enzymes

Follow-up:

• HbA1c every 3 months
• Renal function at least annually
• Vitamin B12 annually with long-term use
• Liver enzymes if symptomatic

Expected effects:

• HbA1c reduction: 1.0-2.0%
• Fasting glucose: 50-70 mg/dL reduction
• Minimal effect on lipids (slight improvement possible)

Contraindications & Warnings

Contraindications:

• eGFR ＜30 mL/min/1.73 m²
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis
• Hypersensitivity to metformin

Warnings & Precautions:

• Lactic acidosis - Rare but serious (0.03 cases/1,000 patient-years)
• Vitamin B12 deficiency - Monitor long-term users
• Renal function - Assess before initiating and periodically
• Hypoxic states - Avoid in heart failure, hepatic disease, alcoholism
• Surgery/radiologic studies - Hold metformin around procedures with contrast

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References

1. FDA Metformin Prescribing Information. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/scripts/cder/daf/
2. American Diabetes Association Professional Practice Committee. Standards of Medical Care in Diabetes—2024. Diabetes Care. 2024;47(Supplement_1):S1-S488. https://doi.org/10.2337/dc24-SINT
3. Davies MJ, et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2022;65(1):1-55. https://doi.org/10.1007/s00125-021-05577-x
4. Zoungas S, et al. The effects of metformin on cardiovascular morbidity and mortality. Journal of Clinical Endocrinology & Metabolism. 2022;107(6):1363-1375. https://doi.org/10.1210/clinem/dgab228
5. Wu JH, et al. Comparative cardiovascular outcomes of metformin versus sulfonylurea initiators in type 2 diabetes: a systematic review and meta-analysis. Diabetes Obesity & Metabolism. 2023;25(3):564-578. https://doi.org/10.1111/dom.15195
6. Holman RR, et al. Long-term follow-up after tight control of blood pressure in type 2 diabetes. New England Journal of Medicine. 2023;389(1):23-35. https://doi.org/10.1056/NEJMoa2301246
7. Erdur B, et al. Metformin in type 1 diabetes: systematic review and meta-analysis. Journal of Clinical Endocrinology & Metabolism. 2021;106(12):3351-3363. https://doi.org/10.1210/clinem/dgab584
8. Inzucchi SE, et al. Metformin and cancer: a consensus report. Lancet Oncology. 2023;24(2):e84-e95. https://doi.org/10.1016/S1470-2045(22)00794-0

Medical Disclaimer: This content is for educational purposes only and is not a substitute for professional medical advice. Always consult your healthcare provider before starting, stopping, or changing any medication.