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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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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 • Inhibits incretin breakdown • Indirectly increase own insulin secretion • Moderate HBA1c reduction (~1%) • Which one to choose?
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 vsThiazolidinedione • DPP-4 Inhibitor if: • Weight gain would cause significant problem • Thiazolidinedione contraindicated • eg heart failure • Previous intolerance or poor response to Thiazolidinedione
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 Effects: • Stimulates post-prandial insulin secretion • Slows gastric emptying • Reduces appetite Administered: • Subcutaneous injection • Twice daily
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
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 • 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