Metformin: Comprehensive Clinical Guide, Mechanism, and Safety Profile

By: [Md Rasel Molla], RPh (Pharmacist) Last Updated: January 2026

Category: Endocrinology / Antidiabetic Agents

---

1. Introduction

Metformin is a biguanide antihyperglycemic agent and remains the first-line pharmacotherapy for the management of Type 2 Diabetes Mellitus (T2DM). It is favored globally for its efficacy, safety profile, and weight-neutral effects.

2. Clinical Indications

• Primary: Type 2 Diabetes Mellitus (Adults and Pediatrics $\ge$ 10 years).
• Off-label Use: Polycystic Ovary Syndrome (PCOS), Prediabetes management, and Gestational Diabetes.

3. Mechanism of Action (Pharmacodynamics)

Metformin works through three primary mechanisms to lower blood glucose levels:

1. Inhibition of Hepatic Gluconeogenesis: It decreases glucose production in the liver.

2. Increased Insulin Sensitivity: It improves peripheral glucose uptake and utilization by muscle tissues.

3. Intestinal Absorption: It slows the absorption of glucose in the gastrointestinal tract.

Pharmacist's Note: Unlike sulfonylureas, Metformin does not stimulate insulin secretion, which significantly reduces the risk of hypoglycemia.

4. Pharmacokinetics

• Absorption: Bioavailability is approximately 50–60%.
• Distribution: Not bound to plasma proteins.
• Metabolism: Not metabolized by the liver (No CYP450 involvement).
• Excretion: 90% is excreted unchanged via the kidneys (Renal clearance).

5. Dosage and Administration

• Standard Starting Dose: 500 mg or 850 mg once or twice daily with meals.
• Maximum Dose: 2,550 mg per day (in divided doses).
• Administration Tip: To minimize Gastrointestinal (GI) side effects, "Start low and go slow" and always take with food.

6. Contraindications and Precautions

• Renal Impairment: Contraindicated if eGFR < 30 mL/min/1.73m².
• Lactic Acidosis: A rare but severe complication. Risk increases in patients with severe renal or hepatic failure.
• Vitamin B12 Deficiency: Long-term use may decrease B12 absorption; periodic monitoring is recommended.

7. Common Side Effects

System	Side Effect
Gastrointestinal	Diarrhea, Nausea, Bloating, Metallic taste
Metabolic	Vitamin B12 deficiency
Dermatological	Rash (rare)

8. Drug-Drug Interactions (DDI)

• Contrast Media: Metformin must be withheld 48 hours before and after procedures involving iodinated contrast to prevent acute renal failure.
• Cimetidine: May increase Metformin plasma levels.
• Alcohol: Increases the risk of lactic acidosis.

9. Patient Counseling (The Pharmacist's Role)

• GI Distress: Inform the patient that nausea/diarrhea usually subsides after the first few weeks.
• Alcohol: Advise avoiding excessive alcohol consumption.
• Compliance: Explain that Metformin helps control diabetes but does not "cure" it; lifestyle changes are still necessary.

---

References:

1. British National Formulary (BNF 86).

2. American Diabetes Association (ADA) Standards of Care 2025.

3. Pharmacotherapy: A Pathophysiologic Approach (DiPiro).