Metformin mechanism MCQs
Practice 15 questions with answers and concise explanations for Pharmacology revision.
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Pharmacology
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Q1. Which action best describes the main glucose-lowering effect of metformin?
- Stimulates pancreatic insulin release
- Reduces hepatic glucose production
- Blocks intestinal glucose absorption completely
- Directly replaces endogenous insulin
Show answer & explanation
Correct answer: B. Reduces hepatic glucose production
Metformin primarily lowers hepatic glucose production and also improves insulin sensitivity.
Q2. What is the primary cellular target and downstream mediator responsible for the glucose-lowering effects of metformin?
- Inhibition of pancreatic ATP-sensitive potassium channels
- Activation of AMP-activated protein kinase (AMPK)
- Stimulation of peroxisome proliferator-activated receptor gamma (PPAR-gamma)
- Blockade of dipeptidyl peptidase-4 (DPP-4)
Show answer & explanation
Correct answer: B. Activation of AMP-activated protein kinase (AMPK)
Metformin primarily exerts its antihyperglycemic effects by activating AMP-activated protein kinase (AMPK), which leads to reduced hepatic glucose production and improved peripheral insulin sensitivity.
Q3. In the liver, how does metformin predominantly lower blood glucose levels?
- Increasing glycogen synthesis while halting glycolysis
- Inhibiting hepatic gluconeogenesis and glycogenolysis
- Stimulating glucagon secretion from alpha cells
- Enhancing intestinal absorption of simple carbohydrates
Show answer & explanation
Correct answer: B. Inhibiting hepatic gluconeogenesis and glycogenolysis
Metformin significantly decreases hepatic glucose output by suppressing both gluconeogenesis and glycogenolysis, largely mediated through AMPK activation and inhibition of mitochondrial glycerophosphate dehydrogenase.
Q4. Which of the following describes a key advantage of metformin therapy compared to sulfonylureas in the management of type 2 diabetes mellitus?
- High incidence of severe hypoglycemia when used as monotherapy
- Substantial weight gain during long-term treatment
- Neutral or modest weight loss without causing hypoglycemia
- Direct stimulation of insulin release from pancreatic beta cells
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Correct answer: C. Neutral or modest weight loss without causing hypoglycemia
Metformin does not stimulate insulin secretion, meaning it carries a very low risk of hypoglycemia when used as monotherapy and is typically associated with weight neutrality or modest weight loss.
Q5. Which organ is the primary site for the clearance and excretion of unchanged metformin?
- Liver
- Kidneys
- Intestines
- Lungs
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Correct answer: B. Kidneys
Metformin is not metabolized by the liver and is eliminated entirely through the kidneys via glomerular filtration and tubular secretion, making renal function crucial to monitor.
Q6. What is the rare but most severe adverse metabolic complication associated with metformin accumulation?
- Diabetic ketoacidosis
- Lactic acidosis
- Hyperosmolar hyperglycemic state
- Non-ketotic hyperosmorphic coma
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Correct answer: B. Lactic acidosis
Metformin can inhibit mitochondrial respiratory chain complex I in hepatocytes, shifting cellular metabolism toward anaerobic glycolysis and predisposing patients to lactic acidosis, especially in the setting of renal impairment.
Q7. How does metformin affect peripheral glucose disposal in skeletal muscle and adipose tissue?
- It decreases insulin receptor expression
- It increases peripheral insulin sensitivity and glucose uptake
- It blocks glucose transporter type 4 (GLUT4) translocation
- It induces peripheral insulin resistance
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Correct answer: B. It increases peripheral insulin sensitivity and glucose uptake
Metformin improves peripheral glucose uptake by activating AMPK, which enhances GLUT4 translocation to the cell surface, thereby increasing insulin-stimulated glucose uptake.
Q8. Which biochemical pathway is directly inhibited by metformin within hepatic mitochondria, contributing to its decreased glucose production?
- Beta-oxidation of fatty acids
- Mitochondrial respiratory chain complex I
- Citric acid cycle (Krebs cycle)
- Pentose phosphate pathway
Show answer & explanation
Correct answer: B. Mitochondrial respiratory chain complex I
Metformin inhibits mitochondrial respiratory chain complex I, which reduces adenosine triphosphate (ATP) production, elevates the AMP/ATP ratio, and subsequently activates AMPK while inhibiting gluconeogenic enzymes.
Q9. Which of the following cellular enzymes is classically activated by therapeutic concentrations of metformin, leading to reduced hepatic glucose production?
- Protein kinase A (PKA)
- AMP-activated protein kinase (AMPK)
- Glycogen synthase kinase 3 (GSK-3)
- HMG-CoA reductase
Show answer & explanation
Correct answer: B. AMP-activated protein kinase (AMPK)
Metformin activates AMP‑activated protein kinase (AMPK) through partial inhibition of mitochondrial complex I, which subsequently downregulates key genes involved in hepatic gluconeogenesis.
Q10. How does metformin primarily influence the risk of hypoglycaemia when used as monotherapy in type 2 diabetes mellitus?
- It significantly stimulates basal insulin secretion from pancreatic beta cells
- It aggressively blocks intestinal glucose absorption leading to reactive hypoglycaemia
- It does not stimulate insulin release, thereby rarely causing hypoglycaemia
- It directly accelerates cellular glucose uptake via permanent GLUT4 translocation
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Correct answer: C. It does not stimulate insulin release, thereby rarely causing hypoglycaemia
Because metformin does not stimulate insulin secretion from the pancreas, it is classified as an euglycaemic agent and carries a very low risk of hypoglycaemia when used alone.
Q11. Which subcellular organelle is the direct primary site of action for metformin's initial inhibitory effect on cellular respiration?
- Endoplasmic reticulum
- Mitochondrion
- Lysosome
- Golgi apparatus
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Correct answer: B. Mitochondrion
Metformin crosses the outer mitochondrial membrane and inhibits mitochondrial complex I (NADH:ubiquinone oxidoreductase), reducing ATP production and altering cellular energy charge.
Q12. Apart from reducing hepatic glucose output, what is a well‑documented secondary systemic effect of metformin therapy on lipid profile parameters?
- Significant elevation of serum triglycerides
- Modest reduction in serum triglycerides and LDL cholesterol
- Severe depletion of high‑density lipoprotein (HDL)
- Complete inhibition of dietary cholesterol emulsification
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Correct answer: B. Modest reduction in serum triglycerides and LDL cholesterol
Metformin frequently produces modest, beneficial improvements in the lipid profile, including reductions in serum triglycerides, total cholesterol, and low‑density lipoprotein (LDL) cholesterol.
Q13. In the gastrointestinal tract, how does metformin contribute to improved glycaemic control beyond its systemic actions?
- By permanently destroying brush‑border disaccharidases
- By slowing gastric emptying and increasing local glucose utilisation by enterocytes
- By causing complete malabsorption of all dietary proteins
- By totally blocking active sodium‑glucose cotransporters in the duodenum
Show answer & explanation
Correct answer: B. By slowing gastric emptying and increasing local glucose utilisation by enterocytes
Metformin slows gastric emptying, enhances GLP‑1 secretion, and reduces intestinal glucose absorption, thereby improving glycaemic control.
Q14. Which of the following clinical conditions represents the strongest absolute contraindication to initiating metformin therapy due to the risk of fatal metabolic toxicity?
- Mild stable chronic obstructive pulmonary disease
- Severe renal impairment with significantly reduced eGFR
- Asymptomatic Gilbert syndrome
- Controlled essential hypertension
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Correct answer: B. Severe renal impairment with significantly reduced eGFR
Metformin is excreted unchanged by the kidneys; severe renal impairment leads to drug accumulation, inhibiting hepatic lactate uptake and precipitating life‑threatening lactic acidosis.
Q15. Long‑term use of metformin at high doses has been clinically associated with the malabsorption and deficiency of which specific micronutrient?
- Vitamin B12
- Folic acid
- Vitamin D3
- Ascorbic acid
Show answer & explanation
Correct answer: A. Vitamin B12
Metformin can interfere with the calcium‑dependent absorption of the vitamin B12‑intrinsic factor complex in the terminal ileum, occasionally leading to megaloblastic anaemia or peripheral neuropathy.
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