Biguanides, primarily metformin, are cornerstone oral antihyperglycemic agents in diabetes pharmacotherapy. This concise guide for B.Pharm students explains metformin’s pharmacodynamics (AMPK activation, mitochondrial complex I inhibition), pharmacokinetics (oral bioavailability, renal excretion, minimal metabolism), clinical uses (type 2 diabetes, PCOS, NAFLD), dosing and formulation differences (IR vs ER), adverse effects (gastrointestinal intolerance, vitamin B12 deficiency, rare lactic acidosis), contraindications (severe renal/hepatic impairment, hypoxia) and key drug interactions (cimetidine, iodinated contrast). Focus on monitoring parameters (eGFR, B12) and mechanisms will strengthen safe, evidence-based use. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which of the following drugs is the prototype biguanide used as first-line therapy in type 2 diabetes?
- Glibenclamide
- Pioglitazone
- Metformin
- Acarbose
Correct Answer: Metformin
Q2. What is the primary cellular mechanism by which metformin decreases hepatic glucose production?
- Direct stimulation of pancreatic beta cells
- Activation of AMP-activated protein kinase (AMPK)
- Inhibition of intestinal carbohydrate digestion
- Direct agonism at insulin receptors
Correct Answer: Activation of AMP-activated protein kinase (AMPK)
Q3. Metformin lowers blood glucose majorly by:
- Increasing renal glucose reabsorption
- Enhancing hepatic gluconeogenesis
- Decreasing hepatic gluconeogenesis
- Stimulating glucagon secretion
Correct Answer: Decreasing hepatic gluconeogenesis
Q4. What is the approximate oral bioavailability of immediate-release metformin in humans?
- 5–10%
- 20–30%
- 50–60%
- 90–100%
Correct Answer: 50–60%
Q5. How is metformin primarily eliminated from the body?
- Hepatic metabolism via CYP450 enzymes
- Renal excretion unchanged
- Metabolism to active metabolites excreted in feces
- Biliary excretion after glucuronidation
Correct Answer: Renal excretion unchanged
Q6. Which transporters are most important for metformin uptake and renal secretion?
- P-glycoprotein and OATP1B1
- OCT2 and MATE transporters
- GLUT4 and SGLT2
- CYP3A4 and CYP2D6
Correct Answer: OCT2 and MATE transporters
Q7. What is the typical plasma elimination half-life of metformin after oral dosing?
- 30 minutes
- 4–8 hours
- 24–48 hours
- 7–14 days
Correct Answer: 4–8 hours
Q8. Metformin is contraindicated in patients with which of the following renal conditions?
- eGFR 75 mL/min/1.73 m2
- eGFR 45 mL/min/1.73 m2
- eGFR <30 mL/min/1.73 m2
- eGFR 60–90 mL/min/1.73 m2
Correct Answer: eGFR <30 mL/min/1.73 m2
Q9. Before administration of iodinated contrast media, what is recommended regarding metformin?
- Continue metformin without interruption
- Double the dose on the day of contrast
- Temporarily discontinue metformin and assess renal function
- Switch to insulin for one year
Correct Answer: Temporarily discontinue metformin and assess renal function
Q10. The most common adverse effects of metformin are:
- Hypoglycemia and weight gain
- Gastrointestinal symptoms (nausea, diarrhea)
- Severe hepatic necrosis
- Dry mouth and tachycardia
Correct Answer: Gastrointestinal symptoms (nausea, diarrhea)
Q11. Long-term metformin therapy is associated with a deficiency in which vitamin?
- Vitamin D
- Vitamin B12
- Vitamin K
- Vitamin C
Correct Answer: Vitamin B12
Q12. Lactic acidosis associated with metformin is:
- Common and mild in most patients
- Nonexistent; metformin cannot cause lactic acidosis
- Rare but serious, risk increased with renal/hepatic impairment and hypoxia
- Prevented by taking metformin with food only
Correct Answer: Rare but serious, risk increased with renal/hepatic impairment and hypoxia
Q13. A commonly used initial dose of immediate-release metformin in adults is:
- 500 mg twice daily
- 10 mg once daily
- 2 g as a single morning dose
- 50 mg intramuscularly
Correct Answer: 500 mg twice daily
Q14. The usual maximum recommended daily dose of metformin (IR/ER) for glycemic control is approximately:
- 500 mg/day
- 1000 mg/day
- 2000 mg/day
- 10,000 mg/day
Correct Answer: 2000 mg/day
Q15. Compared with many other oral antidiabetic drugs, metformin’s effect on body weight is best described as:
- Marked weight gain
- Neutral or modest weight loss
- Severe cachexia
- Induces muscle hypertrophy
Correct Answer: Neutral or modest weight loss
Q16. Besides type 2 diabetes, metformin is commonly used off-label for which endocrine condition?
- Hyperthyroidism
- Polycystic ovary syndrome (PCOS)
- Cushing’s syndrome
- Addison’s disease
Correct Answer: Polycystic ovary syndrome (PCOS)
Q17. Which drug interaction can increase metformin plasma levels by reducing renal clearance?
- Amoxicillin
- Cimetidine
- Vitamin C
- Metoprolol
Correct Answer: Cimetidine
Q18. Which transporter on renal proximal tubule basolateral membrane facilitates cellular uptake of metformin from blood?
- P-glycoprotein
- OCT2 (organic cation transporter 2)
- GLUT2
- OATP1B3
Correct Answer: OCT2 (organic cation transporter 2)
Q19. An advantage of extended-release (ER) metformin formulations over immediate-release (IR) formulations is:
- Increased hepatic metabolism
- Higher peak plasma concentrations causing more GI upset
- Reduced gastrointestinal adverse effects and once-daily dosing
- Greater risk of lactic acidosis in all patients
Correct Answer: Reduced gastrointestinal adverse effects and once-daily dosing
Q20. Metformin’s effect on lipid profile is generally to:
- Greatly increase LDL and triglycerides
- Produce modest decreases in triglycerides and LDL
- Eliminate HDL entirely
- Have no effect on lipids ever
Correct Answer: Produce modest decreases in triglycerides and LDL
Q21. At the mitochondrial level, metformin inhibits which complex, contributing to decreased hepatic ATP production?
- Complex IV (cytochrome c oxidase)
- Complex I (NADH:ubiquinone oxidoreductase)
- ATP synthase exclusively
- Complex II (succinate dehydrogenase)
Correct Answer: Complex I (NADH:ubiquinone oxidoreductase)
Q22. Which laboratory parameter is most important to monitor regularly in patients taking metformin?
- Serum amylase
- Serum creatinine/eGFR
- Thyroid stimulating hormone (TSH)
- Serum potassium
Correct Answer: Serum creatinine/eGFR
Q23. In treatment guidelines, metformin is recommended as first-line therapy for:
- Type 1 diabetes as monotherapy
- Type 2 diabetes unless contraindicated
- All patients with hypertension
- Hyperthyroidism
Correct Answer: Type 2 diabetes unless contraindicated
Q24. Metformin’s glucose-lowering action is NOT due to which of the following?
- Reduction of hepatic glucose output
- Increased peripheral insulin sensitivity
- Direct stimulation of insulin secretion from beta cells
- Activation of AMPK signaling
Correct Answer: Direct stimulation of insulin secretion from beta cells
Q25. Is metformin absolutely contraindicated in pregnancy?
- Yes, absolutely contraindicated in all pregnancies
- No, it is sometimes used in gestational diabetes and PCOS during pregnancy
- Only used topically in pregnancy
- Used only after the first trimester
Correct Answer: No, it is sometimes used in gestational diabetes and PCOS during pregnancy
Q26. Metformin suppresses expression of key gluconeogenic enzymes. Which of the following enzymes is reduced?
- Hexokinase
- Phosphoenolpyruvate carboxykinase (PEPCK)
- Pyruvate kinase
- Acetyl-CoA carboxylase only
Correct Answer: Phosphoenolpyruvate carboxykinase (PEPCK)
Q27. Metformin increases the cellular AMP/ATP ratio primarily by:
- Stimulating ATP synthase activity
- Inhibiting mitochondrial respiratory chain complex I
- Enhancing glycolysis rate only
- Blocking ATP-dependent ion channels in beta cells
Correct Answer: Inhibiting mitochondrial respiratory chain complex I
Q28. Which clinical scenario increases the risk of metformin-associated lactic acidosis and warrants avoidance of metformin?
- Well-controlled hypertension on ACE inhibitor
- Acute myocardial infarction or cardiogenic shock
- Mild osteoarthritis
- Stable hypothyroidism on levothyroxine
Correct Answer: Acute myocardial infarction or cardiogenic shock
Q29. For patients on long-term metformin who develop unexplained neuropathy, which test should be considered?
- Serum vitamin B12 level
- Fasting cortisol
- Anti-nuclear antibody titer
- Serum calcium
Correct Answer: Serum vitamin B12 level
Q30. In cases of severe metformin overdose with lactic acidosis, the most appropriate life-saving intervention is:
- Activated charcoal only
- Immediate hemodialysis to remove metformin and correct acidosis
- Administration of oral glucose
- High-dose corticosteroids
Correct Answer: Immediate hemodialysis to remove metformin and correct acidosis
