Meglitinides

Summary

Meglitinides are a class of drugs that are recognizable by their -Glinide ending. These drugs are used to treat type 2 diabetes mellitus. Mechanistically, these drugs work on the beta cell membrane inside the pancreas. They work by closing potassium channels, which causes depolarization of the cell. This then causes calcium influx into the cell, which leads to the release of both insulin and C-peptide. Side effects of the Meglitinides include weight gain and hypoglycemia. These drugs should be used with caution in patients with renal insufficiency.

Key Points

• Meglitinides
  • Drug Names
    • -glinides
      • Nateglinide
      • Repaglinide
  • Mechanism
    • Acts on beta cells inside the pancreas
    • Multi-step pathway:
      • Close potassium channels
        • Different site than sulfonylureas, leading to a faster onset and shorter duration of action
      • → cell depolarization
        • Via decreased outflow of potassium from the cell
      • → increased calcium influx
        • Via opening of voltage-gated calcium channels
      • → insulin release
        • Intracellular calcium causes fusion of vesicles and release of insulin
      • → increased C-peptide
        • Since increased insulin is endogenous in origin, it is released with C-peptide
  • Clinical Use
    • Treats diabetes mellitus
      • Due to short duration of action, these drugs may be given with meals to reduce post-prandial glucose peaks
  • Side Effects
    • Hypoglycemia
      • Increased risk in renal insufficiency (use with caution)
      • Insulin drives sugar into cells, which removes glucose from the bloodstream. If too much insulin is given, too much glucose can be driven into cells and blood glucose levels can get too low.
    • Weight gain
      • Think of this as insulin driving sugar into cells and fattening them up (increased anabolism)
    • Do not cause sulfa allergies
      • Contrast vs. sulfonylureas