Medicine

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USMLE Step 1

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Diabetes Drugs (in-progress)

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Meglitinides

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Summary

Meglitinides, also known as glinides, are a class of medications used in the treatment of type 2 diabetes. Important drug names to know are repaglinide and nateglinide. Meglitinides work by closing the ATP-dependent potassium channels, thus depolarizing the beta cells of the pancreas. Depolarization of the cell increases intracellular calcium levels by opening voltage-gated calcium channels, and this calcium eventually leads to the release of insulin. Compared to sulfonylureas, glinides have a faster onset and shorter duration of action. Also remember all drugs that increase insulin levels can cause hypoglycemia and weight gain, and meglitinides are no exception. Finally, meglitinides are renally excreted, so increased risk of hypoglycemia can be seen in chronic kidney disease.

Key Points

  • Glinides (Meglitinides)
    • Drugs
      • Nateglinide
      • Repaglinide
    • Mechanism
      • Close ATP-dependent K+ channels
        • Different site than sulfonylureas, which is why they have a faster onset and shorter duration of action (clinical features more relevant for Step 2)
      • beta cell depolarization
      • calcium influx
        • Occurs via voltage-gated calcium channels opening
        • Intracellular calcium causes vesicle fusion and release of vesicle contents
      • insulin release
        • So C-peptide levels also increase
          • C-peptide is also in beta cell vesicles
          • This gives us a way to differentiate between endogenous and exogenous insulin exposure (esp. relevant in factitious hypoglycemia)
    • Clinical Use
      • Type II diabetes
        • Not useful in type I DM because they require some islet function
      • Used as monotherapy or combined with metformin
    • Adverse Effects
      • Hypoglycemia
        • Insulin drives sugar into cells, which removes glucose from the bloodstream. If too much insulin is present, too much glucose can be driven into cells and blood glucose levels can get too low.
      • Weight Gain
        • I like to think of this as insulin driving sugar into cells and fattening them up
      • Side effects are worse in kidney disease
        • Meglitinides are renally-excreted, so in CKD patients they accumulate and can lead to worse side effects
        • Diabetes can cause kidney disease
        • The one to really watch out for is hypoglycemia