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New Diabetes Drugs DPP-4 Inhibitors Exenatide. Incretin effect. GLP -1 (gut hormone) + GIP = incretin effect =Augmentation of insulin after oral glucose Type 2 diabetics little incretin effect Reduced GLP-1 secretion GIP lost insulinotropic property GLP-1 broken down by DPP-4

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New Diabetes Drugs DPP-4 Inhibitors Exenatide


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incretin effect
Incretin effect
  • GLP -1 (gut hormone) + GIP = incretin effect

=Augmentation of insulin after oral glucose

  • Type 2 diabetics little incretin effect
    • Reduced GLP-1 secretion
    • GIP lost insulinotropic property
  • GLP-1 broken down by DPP-4
  • Only for type 2 diabetes
dpp 4 inhibitors sitagliptin vildagliptin
DPP-4 Inhibitors: Sitagliptin, Vildagliptin
  • Inhibits incretin breakdown
  • Indirectly increase own insulin secretion
  • Moderate HBA1c reduction (~1%)
  • Which one to choose?
dpp 4 inhibitors sitagliptin vildagliptin1
DPP-4 Inhibitors: Sitagliptin, Vildagliptin
  • Start
    • 2nd line: Metformin or Sulphonylurea + HBA1c ≥ 6.5% + not suitable for other one
    • 3rd line: Metformin + Sulphonylurea + HBA1c ≥ 7.5%
    • Thiazolidinedione is an alternative in 2nd line case but not 3rd
  • Continue
    • HBA1c reduces by ≥ 0.5% in 6 months
dpp 4 inhibitor vs thiazolidinedione
DPP-4 Inhibitor vsThiazolidinedione
  • DPP-4 Inhibitor if:
    • Weight gain would cause significant problem
    • Thiazolidinedione contraindicated
      • eg heart failure
    • Previous intolerance or poor response to Thiazolidinedione
incretin effect1
Incretin effect
  • GLP -1 (gut hormone) + GIP = incretin effect

=Augmentation of insulin after oral glucose

  • Type 2 diabetics little incretin effect
    • Reduced GLP-1 secretion
    • GIP lost insulinotropic property
  • GLP-1 broken down by DPP-4
  • Only for type 2 diabetes
glp 1 mimetic exenatide
GLP 1 Mimetic - Exenatide

Effects:

  • Stimulates post-prandial insulin secretion
  • Slows gastric emptying
  • Reduces appetite

Administered:

  • Subcutaneous injection
  • Twice daily
exenatide
Exenatide
  • Less hypos compared to insulin
  • BIG benefit of weight loss
  • Only licensed to lower blood sugars, not as weight loss agent
  • Nausea and vomiting
  • £830 per person per year
exenatide1
Exenatide
  • Start:
    • BMI ≥ 35 (+ probs assoc. with high wt)
    • BMI < 35 + insulin unacceptable or weight loss beneficial to co-morbidities
    • Continue Metformin and Sulphonylurea
    • Combination with insulin
  • Continue:
    • HbA1c reduction ≥ 1.0% AND
    • Initial body weight reduction ≥ 3%
conclusion
Conclusion
  • Metformin still first line
  • DPP-4 Inhibitors alternative where Thiazolidinediones were previously only other oral option
  • Exenatide - good for weight loss but ?help in sugar control
  • Further new drugs on their way