Biologic medicines for diabetes MCQs With Answer

Introduction:

This quiz collection on biologic medicines for diabetes is tailored for M.Pharm students studying Biological Evaluation of Drug Therapy. It focuses on therapeutic proteins and peptide biologics used in diabetes management — including insulins, GLP-1 receptor agonists, amylin analogs and emerging immunotherapies — and examines their pharmacology, formulation, stability, immunogenicity, analytical evaluation and regulatory considerations. Each multiple-choice question tests depth of understanding required for formulation development, bioassays, comparability and clinical evaluation of biologics. Use these questions to assess critical thinking on mechanisms, assay selection, post‑marketing safety and the special handling requirements of biologic antidiabetic agents.

Q1. What structural modification primarily accounts for the faster onset of action of insulin lispro compared to regular human insulin?

• Replacement of amino acids that reduce hexamer formation allowing faster absorption
• PEGylation of the insulin molecule increasing circulation time
• Fusion with an Fc fragment to decrease renal clearance
• Glycosylation of the B‑chain increasing receptor affinity

Correct Answer: Replacement of amino acids that reduce hexamer formation allowing faster absorption

Q2. Which analytical approach is most appropriate to determine the biological potency of an insulin preparation during batch release?

• In vivo glucose‑lowering bioassay (standardized animal or cell bioassay referenced to WHO standard)
• Reversed‑phase HPLC quantification of intact insulin mass
• UV spectrophotometry for total peptide content
• Size‑exclusion chromatography for aggregate profile only

Correct Answer: In vivo glucose‑lowering bioassay (standardized animal or cell bioassay referenced to WHO standard)

Q3. Under US regulatory terminology, what additional legal designation must a biosimilar obtain to permit pharmacy-level substitution for a prescribed reference biologic?

• An interchangeability designation demonstrating no loss of safety or efficacy when alternated
• A pediatric exclusivity waiver specific to biosimilars
• Only analytical comparability data without clinical evidence
• A designation as a generic biologic identical in structure to the reference

Correct Answer: An interchangeability designation demonstrating no loss of safety or efficacy when alternated

Q4. Which factor most commonly increases immunogenicity risk of therapeutic peptide and protein formulations?

• Protein aggregates and particles formed during manufacturing or storage
• Low osmolarity of the formulation
• Use of isotonic buffers such as phosphate saline
• High ionic strength improving solubility

Correct Answer: Protein aggregates and particles formed during manufacturing or storage

Q5. What chemical modification gives liraglutide its prolonged half‑life compared with native GLP‑1?

• Fatty‑acid (C16) acylation that promotes reversible albumin binding
• N‑terminal PEGylation increasing molecular size
• Fusion to an Fc domain of IgG to utilize FcRn recycling
• Glycosylation at multiple serine residues

Correct Answer: Fatty‑acid (C16) acylation that promotes reversible albumin binding

Q6. Dulaglutide extends duration of action primarily because it is:

• A GLP‑1 receptor agonist genetically fused to an immunoglobulin Fc fragment to increase half‑life
• A small molecule GLP‑1 mimetic with increased oral bioavailability
• A PEGylated GLP‑1 analogue reducing renal clearance
• An inhaled nanoparticle formulation for pulmonary delivery

Correct Answer: A GLP‑1 receptor agonist genetically fused to an immunoglobulin Fc fragment to increase half‑life

Q7. Pramlintide is used as an adjunct in diabetes therapy; its principal mechanism is:

• An amylin analog that suppresses postprandial glucagon and slows gastric emptying
• An insulin analogue that preferentially activates peripheral glucose uptake
• A DPP‑4 inhibitor that increases endogenous GLP‑1 levels
• An SGLT2 inhibitor that increases urinary glucose excretion

Correct Answer: An amylin analog that suppresses postprandial glucagon and slows gastric emptying

Q8. The International Unit (IU) for insulin potency is defined by:

• Biological activity measured relative to a WHO international reference standard in a standardized bioassay
• Mass concentration in micrograms per milliliter measured by MS
• The molar concentration of insulin peptide chains determined by amino acid analysis
• The total nitrogen content of the formulation

Correct Answer: Biological activity measured relative to a WHO international reference standard in a standardized bioassay

Q9. PEGylation of peptide therapeutics most commonly results in:

• Increased hydrodynamic size, reduced renal clearance and prolonged plasma half‑life
• Increased receptor affinity and faster clearance
• Complete elimination of immunogenicity risk
• Improved oral bioavailability through intestinal uptake

Correct Answer: Increased hydrodynamic size, reduced renal clearance and prolonged plasma half‑life

Q10. Which preservative is commonly used in multi‑dose insulin vials and pens to inhibit microbial growth?

• m‑Cresol (meta‑cresol)
• Sodium azide
• Benzalkonium chloride
• Thiomersal (ethylmercury)

Correct Answer: m‑Cresol (meta‑cresol)

Q11. What is the principal consequence of inadvertent freezing and thawing of protein biologic formulations such as insulin?

• Formation of irreversible aggregates and loss of potency
• Improved sterility due to freeze inactivation of microbes
• Increased receptor affinity from cold‑induced conformational change
• Enhanced aerosolization for inhaled delivery

Correct Answer: Formation of irreversible aggregates and loss of potency

Q12. Which laboratory method is most suitable to detect neutralizing anti‑drug antibodies against a GLP‑1 receptor agonist?

• Cell‑based functional assay measuring inhibition of receptor signaling
• Standard ELISA measuring total binding antibodies only
• Size‑exclusion chromatography for aggregate detection
• Reversed‑phase HPLC for peptide purity

Correct Answer: Cell‑based functional assay measuring inhibition of receptor signaling

Q13. Teplizumab, an investigational biologic for type 1 diabetes delay, targets which immune component?

• CD3 on T lymphocytes to modulate autoreactive T‑cell responses
• Interleukin‑6 to reduce systemic inflammation
• CTLA‑4 to enhance regulatory T‑cell suppression
• TNF‑alpha to block cytokine‑mediated beta‑cell damage

Correct Answer: CD3 on T lymphocytes to modulate autoreactive T‑cell responses

Q14. Insulin glargine’s prolonged, peakless profile after subcutaneous injection is primarily due to:

• Alteration of isoelectric point (addition of two arginines and A21 substitution) causing microprecipitation in subcutaneous tissue
• PEGylation of the B‑chain increasing molecular size
• Conjugation to albumin through a fatty‑acid linker
• Incorporation into biodegradable microspheres for slow release

Correct Answer: Alteration of isoelectric point (addition of two arginines and A21 substitution) causing microprecipitation in subcutaneous tissue

Q15. To characterize site‑specific glycosylation of an Fc‑fusion GLP‑1 product, which analytical technique is most informative?

• LC‑MS/MS glycopeptide mapping (mass spectrometry‑based analysis)
• UV absorbance at 280 nm
• Simple reducing SDS‑PAGE gel electrophoresis
• Potency assay in diabetic animals only

Correct Answer: LC‑MS/MS glycopeptide mapping (mass spectrometry‑based analysis)

Q16. During biosimilar development, which type of data is considered the most sensitive to detect subtle differences from the reference product?

• Comprehensive physicochemical and functional (in vitro) analytical characterization
• Single small pharmacokinetic equivalence study in healthy volunteers only
• Large phase III efficacy trial as the first step
• Post‑marketing adverse event reports exclusively

Correct Answer: Comprehensive physicochemical and functional (in vitro) analytical characterization

Q17. The inhaled insulin formulation Afrezza achieves rapid systemic absorption primarily because it:

• Delivers micronized insulin on an excipient (Technosphere) carrier enabling deep alveolar deposition and rapid dissolution
• Is PEGylated to enhance pulmonary retention
• Contains a liposomal matrix that slowly releases insulin
• Is chemically modified to resist proteolysis in the lung

Correct Answer: Delivers micronized insulin on an excipient (Technosphere) carrier enabling deep alveolar deposition and rapid dissolution

Q18. Which adverse effect is most commonly associated with GLP‑1 receptor agonist therapy in clinical practice?

• Nausea and gastrointestinal upset, particularly during dose escalation
• Severe neutropenia as a frequent complication
• Pulmonary fibrosis in most patients
• Acute cholestatic liver injury as the primary toxicity

Correct Answer: Nausea and gastrointestinal upset, particularly during dose escalation

Q19. What does “U‑100” denote on an insulin vial label?

• One hundred international units of insulin per milliliter of solution
• One hundred milligrams of insulin per vial
• Insulin for 100 days of therapy at standard dosing
• One hundred micrograms per milliliter of insulin

Correct Answer: One hundred international units of insulin per milliliter of solution

Q20. A stability‑indicating analytical test to monitor deamidation and oxidation of an insulin analog during accelerated stability would best include:

• Peptide mapping combined with LC‑MS to identify and quantify chemical modifications
• Simple total protein assay by Bradford reagent only
• Visual inspection for color change only
• Microbial culture testing as the sole assay

Correct Answer: Peptide mapping combined with LC‑MS to identify and quantify chemical modifications

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