Oral hypoglycemic agents: classes and mechanisms MCQs With Answer

Introduction: This quiz collection on oral hypoglycemic agents focuses on classes and mechanisms essential for M.Pharm students in Advanced Pharmacology-II. It covers classical and newer oral antidiabetic drug groups — sulfonylureas, meglitinides, biguanides, thiazolidinediones, alpha‑glucosidase inhibitors, DPP‑4 inhibitors and SGLT2 inhibitors — emphasizing molecular targets, intracellular signaling, pharmacokinetics, adverse effects and clinically relevant interactions. Questions are designed to test mechanistic understanding, drug-specific metabolic pathways, receptor/subunit interactions (e.g., KATP channel subunits), and therapeutic implications such as hypoglycemia, lactic acidosis, heart failure risk and euglycemic DKA. Use these MCQs to deepen mechanistic insight and prepare for advanced exams and clinical decision-making.

Q1. Which of the following best describes the primary mechanism by which sulfonylureas lower blood glucose?

• Activation of AMP-activated protein kinase (AMPK) in hepatocytes
• Inhibition of intestinal alpha-glucosidases to delay carbohydrate absorption
• Binding to the SUR1 subunit of pancreatic beta-cell KATP channels, causing channel closure and insulin release
• Agonism at PPAR-gamma nuclear receptors to increase peripheral insulin sensitivity

Correct Answer: Binding to the SUR1 subunit of pancreatic beta-cell KATP channels, causing channel closure and insulin release

Q2. Meglitinides (repaglinide, nateglinide) differ from sulfonylureas mainly because they:

• Activate PPAR-alpha to increase fatty acid oxidation
• Bind to a distinct site on SUR1 producing rapid, short‑acting insulin secretion stimulated by meals
• Inhibit SGLT2 in the proximal renal tubule causing glucosuria
• Directly inhibit hepatic gluconeogenesis via mitochondrial complex I inhibition

Correct Answer: Bind to a distinct site on SUR1 producing rapid, short‑acting insulin secretion stimulated by meals

Q3. Metformin lowers hepatic glucose production primarily through which intracellular mechanism?

• Direct activation of PPAR-gamma transcriptional activity
• Inhibition of DPP-4 enzyme increasing GLP-1 levels
• Activation of AMPK and inhibition of mitochondrial respiratory complex I leading to reduced gluconeogenesis
• Blocking SGLT1-mediated intestinal glucose absorption

Correct Answer: Activation of AMPK and inhibition of mitochondrial respiratory complex I leading to reduced gluconeogenesis

Q4. Thiazolidinediones (e.g., pioglitazone) exert their insulin-sensitizing effects primarily by:

• Inhibiting alpha-glucosidase enzymes in the gut
• Binding and activating PPAR-gamma nuclear receptors to modify gene transcription in adipose and muscle
• Blocking renal SGLT2 transporters
• Stimulating GLP-1 secretion from intestinal L-cells

Correct Answer: Binding and activating PPAR-gamma nuclear receptors to modify gene transcription in adipose and muscle

Q5. Alpha‑glucosidase inhibitors (e.g., acarbose) reduce postprandial hyperglycemia by:

• Increasing insulin synthesis in pancreatic beta cells
• Delaying carbohydrate digestion by inhibiting intestinal brush-border disaccharidases
• Increasing urinary glucose excretion through SGLT2 inhibition
• Enhancing peripheral glucose uptake via GLUT4 translocation

Correct Answer: Delaying carbohydrate digestion by inhibiting intestinal brush-border disaccharidases

Q6. DPP‑4 inhibitors lower blood glucose mainly by:

• Direct stimulation of insulin gene transcription in beta cells
• Inhibition of dipeptidyl peptidase-4, prolonging incretin hormones (GLP-1 and GIP) and enhancing glucose-dependent insulin secretion
• Blocking hepatic gluconeogenesis via mTOR inhibition
• Increasing renal glucose excretion by blocking SGLT1

Correct Answer: Inhibition of dipeptidyl peptidase-4, prolonging incretin hormones (GLP-1 and GIP) and enhancing glucose-dependent insulin secretion

Q7. SGLT2 inhibitors lower plasma glucose by which renal mechanism?

• Inhibiting glucose reabsorption in the proximal tubule S1 segment, increasing urinary glucose excretion
• Blocking GLUT2 in the basolateral membrane of renal tubular cells
• Stimulating renal gluconeogenesis to reduce circulating insulin
• Increasing tubular insulin secretion to promote glucose excretion

Correct Answer: Inhibiting glucose reabsorption in the proximal tubule S1 segment, increasing urinary glucose excretion

Q8. Which oral antidiabetic drug is most strongly associated with lactic acidosis risk, especially in renal impairment?

• Sitagliptin
• Metformin
• Pioglitazone
• Acarbose

Correct Answer: Metformin

Q9. Among oral hypoglycemic agents, which class commonly causes weight loss as a pharmacologic effect?

• SGLT2 inhibitors
• Sulfonylureas
• Thiazolidinediones
• Meglitinides

Correct Answer: SGLT2 inhibitors

Q10. Which adverse effect is a well-recognized class risk for thiazolidinediones?

• Increased risk of gastrointestinal bleeding
• Fluid retention and exacerbation of heart failure
• Severe hypoglycemia when used as monotherapy
• Marked acute pancreatitis within hours of dosing

Correct Answer: Fluid retention and exacerbation of heart failure

Q11. Combining which oral agent class with insulin most increases the risk of hypoglycemia?

• Alpha-glucosidase inhibitors
• DPP‑4 inhibitors
• Sulfonylureas
• SGLT2 inhibitors

Correct Answer: Sulfonylureas

Q12. Acarbose primarily inhibits which intestinal enzymes?

• SGLT2 transporters
• Brush-border alpha-glucosidases such as sucrase and maltase
• DPP-4 enzyme
• Pancreatic lipase

Correct Answer: Brush-border alpha-glucosidases such as sucrase and maltase

Q13. Which DPP‑4 inhibitor is largely excreted unchanged by the kidney and often requires dose adjustment in renal impairment?

• Saxagliptin
• Sitagliptin
• Alogliptin
• Linagliptin

Correct Answer: Sitagliptin

Q14. SGLT2 inhibitors have been associated with euglycemic diabetic ketoacidosis; a key contributory mechanism is:

• Excessive activation of insulin receptors in adipose tissue
• Glucosuria-induced decrease in insulin secretion and relative increase in glucagon, promoting ketogenesis
• Direct mitochondrial toxicity causing ketone body accumulation
• Inhibition of hepatic glycogenolysis increasing free fatty acid esterification

Correct Answer: Glucosuria-induced decrease in insulin secretion and relative increase in glucagon, promoting ketogenesis

Q15. Which oral SGLT2 inhibitor undergoes significant metabolism by UDP‑glucuronosyltransferases (UGTs) rather than extensive CYP450 oxidation?

• Canagliflozin
• Metformin
• Glipizide
• Acarbose

Correct Answer: Canagliflozin

Q16. Beyond complex I inhibition, metformin has been shown to reduce hepatic gluconeogenesis by inhibiting which enzyme/system?

• HMG-CoA reductase
• Mitochondrial glycerophosphate dehydrogenase
• Renal 11-beta hydroxysteroid dehydrogenase
• Intestinal SGLT1 transporter

Correct Answer: Mitochondrial glycerophosphate dehydrogenase

Q17. Which DPP‑4 inhibitor is substantially metabolized by CYP3A4 and therefore has important drug–drug interactions with strong CYP3A4 inhibitors or inducers?

• Linagliptin
• Sitagliptin
• Saxagliptin
• Alogliptin

Correct Answer: Saxagliptin

Q18. Which sulfonylurea is preferred in elderly patients due to its relatively shorter half-life and lower active metabolite accumulation?

• Glyburide (glibenclamide)
• Chlorpropamide
• Glipizide
• Tolbutamide

Correct Answer: Glipizide

Q19. Which oral antidiabetic agent has been shown to have favorable effects on HDL and triglyceride profiles in clinical studies, particularly pioglitazone?

• Thiazolidinediones (pioglitazone)
• Sulfonylureas
• Alpha-glucosidase inhibitors
• DPP‑4 inhibitors

Correct Answer: Thiazolidinediones (pioglitazone)

Q20. The common gastrointestinal adverse effects (flatulence, bloating, diarrhea) seen with alpha‑glucosidase inhibitors are primarily due to:

• Direct irritation of gastric mucosa by the drug
• Accumulation of unmetabolized carbohydrates in the colon and bacterial fermentation producing gas
• Systemic cholinergic overstimulation
• Enhanced bile acid reabsorption in the ileum

Correct Answer: Accumulation of unmetabolized carbohydrates in the colon and bacterial fermentation producing gas

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