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| Metformin | |
|---|---|
| Brand Names | Glucophage®, Glucophage XR®, Riomet® |
| Drug Class | Biguanide |
| Primary Use | Type 2 Diabetes |
| A1c Reduction | ~1–1.5% |
| Hypoglycemia Risk | Low |
| Weight Effect | Neutral / ↓ |
| Elimination | Renal |
| Black Box | Lactic Acidosis |
| FDA Approval | 1994 |
Metformin (Glucophage®)
Overview
Metformin is a biguanide and first-line pharmacologic therapy for Type 2 Diabetes. It lowers plasma glucose primarily by reducing hepatic glucose production and improving insulin sensitivity without stimulating insulin secretion.
Mechanism of Action
Metformin activates AMP-activated protein kinase (AMPK).
This results in:
- Decreased hepatic gluconeogenesis
- Improved peripheral glucose uptake
- Reduced fasting plasma glucose
Because it does not increase insulin secretion, hypoglycemia is uncommon when used as monotherapy.
Clinical Use
- First-line therapy in most patients with Type 2 Diabetes
- Combination therapy with:
Preferred in overweight patients and in early disease.
Safety
Black Box Warning
Risk of lactic acidosis.
Increased risk in:
- eGFR < 30 mL/min/1.73m²
- Severe hepatic impairment
- Hypoxic states
- Acute illness or dehydration
Contraindications
- eGFR < 30
- Acute metabolic acidosis
Dosing
Initial: 500 mg daily Titrate weekly Typical: 1500–2000 mg/day Reduce dose if eGFR 30–45 Avoid if eGFR < 30
Pharmacokinetics
Absorption: ~50–60% Metabolism: None Half-life: ~6 hours Elimination: Renal (unchanged)
Adverse Effects
Common:
- Gastrointestinal upset
- Diarrhea
- Metallic taste
Long-term:
- Vitamin B12 deficiency
Serious:
- Lactic acidosis (rare)
Comparison Within Class
Metformin is the only clinically used biguanide.
Compared with:
- Sulfonylureas → no hypoglycemia
- GLP-1 receptor agonists → less weight loss
- SGLT2 inhibitors → no heart failure or CKD benefit