Metformin

What is Metformin?

Metformin is a biguanide antidiabetic medication primarily used in the management of type 2 diabetes mellitus. It lowers blood glucose levels without stimulating insulin secretion, which significantly reduces the risk of hypoglycemia.

Because of its effectiveness, safety profile, and cardiovascular benefits, metformin is considered the cornerstone of type 2 diabetes therapy worldwide.

History & Background

Metformin traces its origins to the plant Galega officinalis, which contains guanidine compounds known to lower blood glucose. Modern metformin was developed to retain glucose-lowering effects while minimizing toxicity, eventually becoming the most prescribed antidiabetic drug globally.

Chemical Structure & Medicinal Chemistry

• IUPAC: N,N-dimethylimidodicarbonimidic diamide
• Molecular Formula: C₄H₁₁N₅
• Molar Mass: 129.16 g/mol
• Functional Group: Biguanide

The highly polar biguanide structure limits lipid solubility, which explains metformin’s minimal hepatic metabolism and lack of central nervous system effects.

Mechanism of Action

Metformin primarily acts by activating AMP-activated protein kinase (AMPK), a key cellular energy regulator. This results in reduced hepatic glucose production and improved insulin sensitivity.

• Decreases hepatic gluconeogenesis
• Improves peripheral insulin sensitivity
• Reduces intestinal glucose absorption

Unlike many antidiabetic drugs, metformin does not increase insulin secretion, which explains its low hypoglycemia risk.

Pharmacokinetics

• Oral bioavailability ~50–60%
• Peak plasma concentration within 2–3 hours
• Negligible protein binding
• Not metabolized in the liver
• Excreted unchanged via kidneys

Clinical Uses

• Type 2 diabetes mellitus
• Insulin resistance
• Polycystic ovary syndrome (PCOS)
• Prevention of diabetes progression in high-risk individuals

Safety and Responsible Use

Metformin is generally well tolerated. Gastrointestinal side effects are common initially but often improve with gradual dose escalation and administration with meals.

Common Side Effects

• Nausea
• Diarrhea
• Abdominal discomfort
• Metallic taste
• Vitamin B₁₂ deficiency with long-term use

Lactic Acidosis Risk

Lactic acidosis is a rare but serious complication associated with metformin accumulation, particularly in patients with impaired kidney function. Proper patient selection and dose adjustment greatly reduce this risk.

Who Should Use Caution?

• Patients with severe kidney disease
• Individuals with severe liver impairment
• Patients with conditions causing hypoxia
• Before iodinated contrast imaging procedures

Drug Interactions

• Alcohol — increased lactic acidosis risk
• Iodinated contrast media
• Cimetidine — reduced renal clearance

References

• World Health Organization (WHO)
• American Diabetes Association (ADA)
• U.S. Food and Drug Administration (FDA)
• PubChem Database
• National Center for Biotechnology Information (NCBI)