Generic Name

Metformin

Mechanism

• Metformin (Glucophage) primarily lowers fasting glucose by inhibiting hepatic gluconeogenesis.
• Enhances peripheral insulin sensitivity through activation of adenosine monophosphate‑activated protein kinase (AMPK), leading to increased glucose uptake and reduced lipid synthesis.
• Reduces intestinal glucose absorption (≈10 % effect).
• *Overall:* improves glycemic control with minimal risk of hypoglycemia when used alone.

Pharmacokinetics

• Absorption: Oral bioavailability ~ 50 %; peak plasma concentrations 1–2 h after dosing.
• Distribution: Widely distributed; low plasma protein binding (< 5 %).
• Elimination: Primarily renal unchanged (≈ 70 %); half‑life ≈ 5 h.
• Excretion: Requires functional renal filtration; not metabolized, making dose adjustments straightforward in renal impairment.

Indications

• Type 2 diabetes mellitus as monotherapy or in combination with other agents.
• Prediabetes and impaired glucose tolerance (to delay progression).
• Polycystic ovary syndrome (PCOS) with insulin resistance (improves ovulatory function).
• Adjunct to lifestyle modification for weight‑neutral or weight‑losing effect.

Contraindications

• Renal impairment: eGFR < 30 mL/min/1.73 m² (use with caution up to 30–60 mL/min).
• Acute or chronic metabolic acidosis (e.g., diabetic ketoacidosis).
• Severe hepatic disease or cirrhosis (risk of lactic acidosis).
• Recent gastrointestinal surgery affecting absorption.
• Pregnancy: Category B—use only if benefits outweigh risks; avoid in lactation due to insufficient safety data.
• Liver transplantation recipients: caution until stable.

Warnings:
• Lactic acidosis: rare but life‑threatening; symptoms include myalgia, abdominal pain, tachypnea.
• Vitamin B12 deficiency: chronic use can impair absorption.
• Hypoglycemia: unlikely alone; increased risk with sulfonylureas or insulin.

Dosing

• Key tip: Start low, slow titration; stop temporarily if dehydration/renal compromise occurs.

Adverse Effects

• Common (GI): nausea, vomiting, diarrhea, abdominal discomfort, metallic taste.
• Serious:
• Lactic acidosis (rare, < 10 cases/100,000 patient‑years).
• Severe B12 deficiency (requires monitoring).
• Other:
• Weight loss (beneficial).
• Hypotension rare (especially with dehydration).
• Rash, itching sometimes.

Monitoring

• Baseline & periodic labs:
• Serum creatinine/eGFR (baseline, then 3–6 months, or earlier if clinically indicated).
• Hemoglobin A1c (baseline, 3 months, then every 6 months).
• Fasting glucose.
• B12 levels after 12 months of therapy.
• Clinical assessment:
• Electrolytes, liver function tests (baseline).
• Watch for signs of lactic acidosis (dyspnea, malaise).

Clinical Pearls

1. “Take it with food” mantra: Improves GI tolerance without compromising efficacy.
2. Renal function check is non‑negotiable: Each dose above 850 mg/day mandates an eGFR > 45 mL/min/1.73 m².
3. Metformin is not a hypoglycemic agent alone – you can safely titrate higher doses without the same risk seen with sulfonylureas.
4. PCOS benefit: A 12‑week regimen improves ovulation rates by ~ 40 % and can reduce androgen levels.
5. B12 monitoring: An easy, inexpensive blood test (measured by serum B12 or methylmalonic acid) can pre‑empt neuropathy before it sets in.
6. ER vs IR: ER offers better GI tolerability but still requires careful titration; consider patient adherence patterns when choosing.
7. Safety in pregnancy: If a patient becomes pregnant while on metformin, discuss discontinuation or switching to insulin, noting that no definitive teratogenic data exist.

*(These pearls distilled from key clinical trials and guidelines to aid rapid recall for students and providers.)*