Introduction: Antidiabetic agents encompass diverse drug classes—insulins, oral hypoglycemics (sulfonylureas, biguanides, thiazolidinediones, meglitinides), alpha-glucosidase inhibitors, incretin-based drugs (GLP-1 analogues, DPP-4 inhibitors) and SGLT2 inhibitors—used to manage diabetes mellitus. This topic covers classification, mechanisms of action, structure–activity relationships (SAR), pharmacokinetics, clinical uses, adverse effects and important drug interactions. Understanding SAR helps predict potency and selectivity, while mechanism knowledge guides rational therapy for type 1 and type 2 diabetes. Emphasis on examples (metformin, glibenclamide, pioglitazone, sitagliptin, empagliflozin) clarifies clinical choice. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which antidiabetic class primarily lowers blood glucose by inhibiting hepatic gluconeogenesis?
- Sulfonylureas
- Biguanides
- Thiazolidinediones
- Alpha-glucosidase inhibitors
Correct Answer: Biguanides
Q2. What is the primary mechanism of action of sulfonylureas?
- Inhibition of SGLT2 in the kidney
- Activation of PPAR-gamma receptors
- Closing pancreatic beta-cell K-ATP channels to stimulate insulin release
- Inhibition of DPP-4 enzyme
Correct Answer: Closing pancreatic beta-cell K-ATP channels to stimulate insulin release
Q3. Which structural feature is essential for classical sulfonylurea activity (SAR)?
- Thiazolidinedione ring
- Sulfonylurea moiety (sulfonyl–urea linkage)
- Biguanide chain
- Glucopyranose ring
Correct Answer: Sulfonylurea moiety (sulfonyl–urea linkage)
Q4. Which drug is a first-line therapy for most patients with type 2 diabetes due to insulin-sensitizing effect?
- Glibenclamide (glyburide)
- Metformin
- Pioglitazone
- Sitagliptin
Correct Answer: Metformin
Q5. Thiazolidinediones (TZDs) exert glucose-lowering effects mainly through which target?
- SGLT2 transporters in proximal tubule
- PPAR-gamma nuclear receptor
- Alpha-glucosidase enzyme in gut
- GLP-1 receptors on beta cells
Correct Answer: PPAR-gamma nuclear receptor
Q6. Which adverse effect is classically associated with metformin in patients with renal impairment?
- Severe hypoglycemia
- Lactic acidosis
- Pancreatitis
- Thyroid dysfunction
Correct Answer: Lactic acidosis
Q7. SGLT2 inhibitors reduce plasma glucose by acting on what part of the nephron?
- Loop of Henle
- Distal convoluted tubule
- Proximal convoluted tubule (S1 segment)
- Collecting duct
Correct Answer: Proximal convoluted tubule (S1 segment)
Q8. Which class’s SAR requires a thiazolidinedione ring for PPAR-gamma agonism?
- Sulfonylureas
- Biguanides
- Thiazolidinediones
- Meglitinides
Correct Answer: Thiazolidinediones
Q9. DPP-4 inhibitors improve glycemic control primarily by:
- Blocking intestinal glucose absorption
- Prolonging action of endogenous incretins (GLP-1, GIP)
- Stimulating insulin gene transcription directly
- Inhibiting renal glucose filtration
Correct Answer: Prolonging action of endogenous incretins (GLP-1, GIP)
Q10. Which drug class is most associated with weight loss among antidiabetic therapies?
- GLP-1 receptor agonists
- Sulfonylureas
- Thiazolidinediones
- Insulin (basal)
Correct Answer: GLP-1 receptor agonists
Q11. For sulfonylureas, increasing lipophilicity at the N-alkyl side chain generally leads to:
- Decreased potency and faster elimination
- Increased potency and longer duration
- Specific renal targeting only
- Loss of hypoglycemic activity
Correct Answer: Increased potency and longer duration
Q12. Which antidiabetic agent works by inhibiting intestinal alpha-glucosidases to delay carbohydrate absorption?
- Acarbose
- Repaglinide
- Canagliflozin
- Rosiglitazone
Correct Answer: Acarbose
Q13. A major risk with sulfonylureas is hypoglycemia due to:
- Excess renal glucose excretion
- Persistent insulin release independent of glucose
- Direct inhibition of glucagon secretion only
- Increased insulin sensitivity only
Correct Answer: Persistent insulin release independent of glucose
Q14. Which class’s mechanism involves mimicking GLP-1 and stimulating glucose-dependent insulin secretion?
- DPP-4 inhibitors
- GLP-1 receptor agonists (incretin mimetics)
- Meglitinides
- Biguanides
Correct Answer: GLP-1 receptor agonists (incretin mimetics)
Q15. Which drug is a rapid-acting insulin secretagogue used at mealtimes?
- Glipizide
- Repaglinide
- Pioglitazone
- Sitagliptin
Correct Answer: Repaglinide
Q16. Which structural element is crucial for thiazolidinediones’ SAR to maintain activity?
- Carboxylic acid at para position of a phenyl ring
- Biguanide functionality
- Thiazolidinedione (TZD) ring with a carbonyl pattern
- Sulfonylurea linkage
Correct Answer: Thiazolidinedione (TZD) ring with a carbonyl pattern
Q17. SGLT2 inhibitors commonly cause which adverse effect due to glycosuria?
- Urinary/genital mycotic infections
- Pancreatitis
- Severe hypoglycemia in monotherapy
- Macrocytic anemia
Correct Answer: Urinary/genital mycotic infections
Q18. Which antidiabetic agent is contraindicated or used cautiously in renal impairment because of increased risk of lactic acidosis?
- Metformin
- Gliclazide
- Acarbose
- Exenatide
Correct Answer: Metformin
Q19. Which class decreases insulin resistance primarily in adipose tissue and muscle by gene transcription changes?
- Thiazolidinediones
- Meglitinides
- DPP-4 inhibitors
- Alpha-glucosidase inhibitors
Correct Answer: Thiazolidinediones
Q20. Which drug example is a DPP-4 inhibitor?
- Sitagliptin
- Empagliflozin
- Glibenclamide
- Pioglitazone
Correct Answer: Sitagliptin
Q21. Meglitinides differ from sulfonylureas mainly by:
- Longer duration and greater hypoglycemia risk
- Rapid onset and short duration of insulin secretion stimulation
- Primary action on renal glucose transporters
- Being PPAR-gamma agonists
Correct Answer: Rapid onset and short duration of insulin secretion stimulation
Q22. Which oral agent’s SAR includes a guanidine-derived biguanide moiety?
- Metformin
- Glipizide
- Rosiglitazone
- Canagliflozin
Correct Answer: Metformin
Q23. Which antidiabetic drug class increases urinary glucose excretion independent of insulin?
- SGLT2 inhibitors
- DPP-4 inhibitors
- Sulfonylureas
- Thiazolidinediones
Correct Answer: SGLT2 inhibitors
Q24. Which drug is an example of an alpha-glucosidase inhibitor?
- Acarbose
- Repaglinide
- Empagliflozin
- Exenatide
Correct Answer: Acarbose
Q25. Which patient scenario is least appropriate for prescribing a sulfonylurea?
- Young patient with type 2 diabetes and preserved renal function
- Elderly patient prone to irregular meals and hypoglycemia
- Patient requiring cheap oral therapy with documented hyperinsulinemia
- Patient with sulfonamide allergy (sulfonylurea hypersensitivity)
Correct Answer: Patient with sulfonamide allergy (sulfonylurea hypersensitivity)
Q26. Which antidiabetic class is most likely to worsen heart failure due to fluid retention?
- Thiazolidinediones
- SGLT2 inhibitors
- Alpha-glucosidase inhibitors
- DPP-4 inhibitors
Correct Answer: Thiazolidinediones
Q27. A key SAR insight for SGLT2 inhibitors is that C-aryl glycoside linkage improves:
- Oral bioavailability and SGLT2 selectivity
- PPAR-gamma activation
- Inhibition of DPP-4 enzyme
- Pancreatic insulin release
Correct Answer: Oral bioavailability and SGLT2 selectivity
Q28. Combination therapy of metformin and which class provides complementary mechanisms (hepatic and renal/incretin effects)?
- Sulfonylureas only
- SGLT2 inhibitors or DPP-4 inhibitors/GLP-1 analogues
- Thiazolidinediones only
- Alpha-glucosidase inhibitors only
Correct Answer: SGLT2 inhibitors or DPP-4 inhibitors/GLP-1 analogues
Q29. Which adverse effect is particularly associated with GLP-1 receptor agonists?
- Severe hypoglycemia without insulin
- Nausea and delayed gastric emptying
- Renal glycosuria
- Bone marrow suppression
Correct Answer: Nausea and delayed gastric emptying
Q30. From a SAR perspective, sulfonylurea potency is enhanced by which aromatic ring substitution?
- Electron-withdrawing para-substituents increasing receptor binding
- Removal of the sulfonyl group
- Introduction of a polar sugar moiety
- Replacement of urea with guanidine
Correct Answer: Electron-withdrawing para-substituents increasing receptor binding
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.
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