Nateglinide MCQs With Answer

Nateglinide MCQs With Answer

Nateglinide is an oral meglitinide-class hypoglycemic agent used in type 2 diabetes to stimulate rapid insulin release from pancreatic beta cells. This concise review for B.Pharm students covers mechanism of action, pharmacokinetics (absorption, Tmax, half-life, bioavailability), metabolism, dosing with meals, adverse effects (hypoglycaemia, weight gain), drug interactions, renal and hepatic considerations, formulation and stability issues, and comparative aspects versus repaglinide and sulfonylureas. Emphasis is placed on therapeutic monitoring, pharmacology, and pharmaceutical aspects relevant to dosage form design and clinical use. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary mechanism of action of nateglinide?

• Inhibition of hepatic gluconeogenesis
• Activation of pancreatic beta-cell KATP channels
• Closing of pancreatic beta-cell KATP channels to stimulate insulin release
• Increasing peripheral insulin receptor sensitivity

Correct Answer: Closing of pancreatic beta-cell KATP channels to stimulate insulin release

Q2. To which drug class does nateglinide belong?

• Sulfonylureas
• Biguanides
• Meglitinides
• Thiazolidinediones

Correct Answer: Meglitinides

Q3. Nateglinide is most appropriately administered:

• Once daily before bedtime
• Before each main meal to control postprandial glucose
• Only in the fasting state
• Only after meals to prevent delayed hypoglycemia

Correct Answer: Before each main meal to control postprandial glucose

Q4. Which pharmacokinetic property best describes nateglinide?

• Long half-life (>24 hours) with sustained action
• Rapid absorption with short half-life (approximately 1–2 hours)
• Poor oral bioavailability due to extensive first-pass elimination
• Predominantly excreted unchanged in urine

Correct Answer: Rapid absorption with short half-life (approximately 1–2 hours)

Q5. Major metabolic pathway for nateglinide is via:

• Renal glucuronidation
• CYP450-mediated hepatic metabolism (mainly CYP2C9 and CYP3A4)
• Hydrolysis by plasma esterases
• Metabolism primarily by CYP2C8

Correct Answer: CYP450-mediated hepatic metabolism (mainly CYP2C9 and CYP3A4)

Q6. Which adverse effect is most commonly associated with nateglinide therapy?

• Hypoglycemia
• Severe lactic acidosis
• Hepatotoxicity in all patients
• Thyroid dysfunction

Correct Answer: Hypoglycemia

Q7. Which patient characteristic increases risk of prolonged hypoglycemia with nateglinide?

• Renal impairment reducing clearance
• Young, healthy adults
• Short postprandial period
• Concurrent metformin therapy

Correct Answer: Renal impairment reducing clearance

Q8. Compared with sulfonylureas, nateglinide generally has:

• Longer duration of action and greater risk of weight gain
• Shorter onset and shorter duration, targeting postprandial glucose
• Stronger binding to albumin causing drug displacement interactions
• Higher incidence of allergic skin reactions

Correct Answer: Shorter onset and shorter duration, targeting postprandial glucose

Q9. The typical clinical indication for nateglinide is:

• Type 1 diabetes as monotherapy
• Type 2 diabetes with predominant postprandial hyperglycaemia
• Gestational diabetes first-line therapy
• Diabetic ketoacidosis management

Correct Answer: Type 2 diabetes with predominant postprandial hyperglycaemia

Q10. Which laboratory parameter should be routinely monitored during nateglinide therapy?

• Serum creatinine and blood glucose/HbA1c
• Thyroid-stimulating hormone
• Amylase and lipase
• Serum potassium only

Correct Answer: Serum creatinine and blood glucose/HbA1c

Q11. Food effect on nateglinide absorption is best described as:

• No effect — can be taken any time regardless of meals
• Reduced absorption with food; take on an empty stomach
• Administration immediately before meals improves postprandial control despite some food delay in Tmax
• Significantly increased bioavailability with fatty meals causing toxicity

Correct Answer: Administration immediately before meals improves postprandial control despite some food delay in Tmax

Q12. Nateglinide binding site on the beta-cell KATP channel is most closely associated with which receptor subtype?

• SUR1 (sulfonylurea receptor 1)
• SUR2B exclusively
• GLUT2 receptor
• Insulin receptor substrate-1

Correct Answer: SUR1 (sulfonylurea receptor 1)

Q13. Which drug interaction is most relevant for nateglinide due to CYP metabolism?

• Fluconazole (CYP inhibitor) increasing nateglinide levels
• Metformin causing competitive protein binding displacement
• Warfarin increasing renal clearance of nateglinide
• Vitamin D supplements reducing nateglinide efficacy

Correct Answer: Fluconazole (CYP inhibitor) increasing nateglinide levels

Q14. In patients with hepatic impairment, nateglinide dosing considerations include:

• No dose adjustment required for severe hepatic failure
• Decrease dose or avoid use in significant hepatic impairment due to reduced metabolism
• Increase dose because of reduced protein binding
• Switch to intravenous nateglinide formulation

Correct Answer: Decrease dose or avoid use in significant hepatic impairment due to reduced metabolism

Q15. Which formulation-related property is most important when designing an immediate-release tablet of nateglinide?

• Controlled-release coating to prolong action
• Rapid disintegration and dissolution to match meal timing
• Enteric coating to prevent stomach irritation
• High mucoadhesive matrix for buccal delivery

Correct Answer: Rapid disintegration and dissolution to match meal timing

Q16. Which of the following best describes nateglinide’s protein binding?

• Negligible protein binding (<5%)
• Moderate protein binding (~98%) causing many interactions
• Moderate protein binding (~98%) is incorrect; actual binding is about 98% which is high
• High protein binding (~98%) — potential for displacement interactions with some drugs

Correct Answer: High protein binding (~98%) — potential for displacement interactions with some drugs

Q17. Which monitoring is most useful to assess long-term glycemic control in a patient on nateglinide?

• Daily postprandial glucose only
• HbA1c measured every 2–3 months
• Serum insulin levels monthly
• Fasting C-peptide weekly

Correct Answer: HbA1c measured every 2–3 months

Q18. Which statement about nateglinide half-life and dosing frequency is correct?

• Long half-life allows once-weekly dosing
• Short half-life requires dosing before each meal (three times daily)
• Half-life increases with food so dosing once daily is sufficient
• Half-life is irrelevant to dosing frequency

Correct Answer: Short half-life requires dosing before each meal (three times daily)

Q19. In formulation stability studies, a major degradation concern for nateglinide is:

• Hydrolysis under acidic or basic conditions
• Nitrosation forming carcinogens
• Oxidative decarboxylation to active metabolite
• Polymerization to form insoluble complexes

Correct Answer: Hydrolysis under acidic or basic conditions

Q20. Combining nateglinide with which antihyperglycemic increases risk of hypoglycemia?

• Metformin alone (no increased hypoglycemia risk)
• Sulfonylurea therapy due to additive insulin secretory effects
• Thiazolidinedione monotherapy reduces hypoglycemia risk
• Alpha-glucosidase inhibitor only increases GI side effects

Correct Answer: Sulfonylurea therapy due to additive insulin secretory effects

Q21. Which patient population is nateglinide generally not recommended for?

• Elderly with careful monitoring
• Pregnant women due to limited safety data
• Type 2 diabetics with postprandial hyperglycemia
• Patients intolerant to metformin needing additional postprandial control

Correct Answer: Pregnant women due to limited safety data

Q22. The onset of action of nateglinide after oral administration is approximately:

• Within 10–30 minutes
• After 12–24 hours
• 3–5 days to see any effect
• Immediately on contact with saliva

Correct Answer: Within 10–30 minutes

Q23. A pharmaceutical analyst developing an assay for nateglinide in plasma should choose which technique for sensitivity and specificity?

• UV spectrophotometry without extraction
• LC-MS/MS with sample preparation
• Turbidimetric assay
• Colorimetric assay using pH indicator

Correct Answer: LC-MS/MS with sample preparation

Q24. Which physicochemical property of nateglinide is important for oral formulation design?

• Very high aqueous solubility making dissolution negligible
• Poor water solubility requiring solubilization strategies
• Gaseous at room temperature enabling inhalation
• Strongly ionic at physiological pH preventing absorption

Correct Answer: Poor water solubility requiring solubilization strategies

Q25. Which regulatory consideration is most relevant when registering a generic nateglinide tablet?

• Demonstration of bioequivalence to the reference product
• Only matching tablet color is required
• No clinical data or bioequivalence studies are needed
• Proving superiority in glycemic control over reference

Correct Answer: Demonstration of bioequivalence to the reference product

Q26. The most appropriate action for a missed dose of nateglinide (taken with meals) is:

• Double the next dose to compensate
• Skip the missed dose if the next meal is near and resume usual schedule
• Take the missed dose several hours later irrespective of meals
• Stop medication permanently

Correct Answer: Skip the missed dose if the next meal is near and resume usual schedule

Q27. In preformulation studies, which parameter helps predict nateglinide’s absorption rate?

• Melting point and partition coefficient (log P)
• Color of the powder
• Manufacturer’s country of origin
• Tablet imprint code

Correct Answer: Melting point and partition coefficient (log P)

Q28. Which statement about weight change with nateglinide is correct?

• Nateglinide consistently causes significant weight loss
• There is potential for weight gain similar to other insulin secretagogues
• Weight is unaffected because it blocks appetite receptors
• Weight fluctuation is only due to water retention

Correct Answer: There is potential for weight gain similar to other insulin secretagogues

Q29. For a B.Pharm student studying pharmacodynamics, which concept is key to understanding nateglinide’s glucose-lowering effect?

• Augmentation of renal glucose excretion
• Time-dependent stimulation of insulin release proportional to glucose concentration
• Permanent regeneration of pancreatic beta-cells
• Inhibition of intestinal glucose absorption by binding starch

Correct Answer: Time-dependent stimulation of insulin release proportional to glucose concentration

Q30. Which contraindication is absolute for nateglinide use?

• Type 2 diabetes with postprandial hyperglycaemia
• Patients with diabetic ketoacidosis
• Mild renal impairment
• Use with diet and exercise only

Correct Answer: Patients with diabetic ketoacidosis

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com