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    Subjects/Pharmacology/Insulin and Oral Hypoglycemics
    Insulin and Oral Hypoglycemics
    easy
    pill Pharmacology

    Which of the following oral hypoglycemic agents acts primarily by inhibiting dipeptidyl peptidase-4 (DPP-4)?

    A. Pioglitazone
    B. Gliclazide
    C. Sitagliptin
    D. Acarbose

    Explanation

    ## DPP-4 Inhibitors: Mechanism and Classification **Key Point:** DPP-4 inhibitors (gliptins) are a class of oral hypoglycemic agents that work by inhibiting the enzyme dipeptidyl peptidase-4, which normally degrades incretin hormones (GLP-1 and GIP). ### Mechanism of Action DPP-4 inhibitors prevent the breakdown of incretin hormones, leading to: 1. Increased GLP-1 and GIP levels 2. Enhanced glucose-dependent insulin secretion 3. Reduced glucagon secretion (only when blood glucose is elevated) 4. Improved postprandial glucose control ### DPP-4 Inhibitors (Gliptins) | Agent | Characteristics | Notes | |-------|-----------------|-------| | **Sitagliptin** | First-in-class DPP-4 inhibitor | Oral, once-daily dosing | | **Vildagliptin** | Rapid onset | Twice-daily dosing | | **Saxagliptin** | Long-acting | Once-daily dosing | | **Linagliptin** | Renal-independent | Safe in renal failure | **High-Yield:** Sitagliptin is the most commonly tested DPP-4 inhibitor in NEET PG exams and is the prototypical agent of this class. ### Comparison with Other Oral Hypoglycemics | Class | Mechanism | Example | |-------|-----------|----------| | **DPP-4 Inhibitors** | Inhibit DPP-4 enzyme | Sitagliptin | | **Thiazolidinediones** | PPAR-γ agonists | Pioglitazone | | **Sulfonylureas** | K-ATP channel blockers | Gliclazide | | **Alpha-glucosidase inhibitors** | Slow carbohydrate absorption | Acarbose | **Clinical Pearl:** DPP-4 inhibitors are weight-neutral and have a low hypoglycemia risk when used as monotherapy, making them suitable for elderly patients and those with renal impairment.

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