Metformin
First-line pharmacotherapy for most individuals with Type 2 Diabetes Mellitus (T2DM), particularly those who are overweight or obese. Also used off-label in polycystic ovary syndrome (PCOS) and metabolic syndrome.
Efficacy
- Lowers HbA1c by 1.5–2.0% (approximately 15–22 mmol/mol)
- Improves fasting plasma glucose and postprandial glycaemic control
Clinical Benefits
- Extensive safety record: Over 50 years of use with well-established tolerability
- Cardiovascular benefit:
- UKPDS 34: Significant reduction in myocardial infarction and all-cause mortality in overweight T2DM patients
- Weight profile: Generally weight neutral or may produce modest weight loss
- Low hypoglycaemia risk:
- Safe as monotherapy since it does not stimulate insulin secretion
Mechanism of Action
- ↓ Hepatic glucose production via inhibition of gluconeogenesis
- ↑ Insulin sensitivity in peripheral tissues, particularly skeletal muscle
- ↓ Intestinal glucose absorption, contributing to improved postprandial glucose levels
Adverse Effects
A. Common (dose-related, often transient):
- Gastrointestinal:
- Nausea, anorexia, abdominal discomfort, diarrhoea
- Incidence: Up to 30%, typically resolves with gradual dose titration
- Mitigation strategies:
- Administer with meals
- Consider extended-release (XR) formulation
B. Rare but serious:
- Lactic Acidosis
- Incidence: ~3–10 cases per 100,000 patient-years
- Risk factors:
- Renal impairment (eGFR <30 mL/min/1.73 m² – absolute contraindication)
- Hepatic dysfunction
- Hypoxic states (e.g. heart failure, sepsis)
- Use of iodinated contrast (withhold metformin 48 hours before and after administration)
- Symptoms: Malaise, myalgia, respiratory distress, somnolence