Oral Antidiabetic Agents

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giddyupp
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70545
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Oral Antidiabetic Agents
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2011-03-03 20:27:28
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Oral Antidiabetic Agents PHPR523 Test4
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Oral Antidiabetic Agents
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  1. What are the classes of oral agents used to treat diabetes and what are their MOA?
    • Biguanides: inhibit gluconeogenesis, improve insulin sensitivity, decrease intestinal absorption of glucose
    • Secretagogues: increase insulin secretion from pancreas (meglitinides are glucose-dependent, sulfonylureas are not)
    • DPP-4 inhibitors: increase glucose-dependent insulin secretion from pancreas, decrease glucagon secretion from alpha cells to decrease gluconeogenesis
    • Thiazolidinediones (PPAR agonists): increase insulin sensitivity, decrease hepatic glucose output
    • Alpha-glucosidase inhibitors: inhibit carbohydrate aborption in intestines
  2. What are the biguanides used in diabetes?
    Metformin
  3. What is the expected A1c reduction from Metformin?
    1-2%
  4. What are the secretagogues used in diabetes?
    • Sulfonylureas:
    • Glyburide
    • Glipizide
    • Glimepiride
    • Meglitinides:
    • Repaglinide
    • Nateglinide
  5. What is the expected A1c reduction from the secretagogues?
    • Sulfonylureas: 1-2%
    • Meglitinides: 1-2% (0.5-1.5% for Nateglinide
  6. What are the DPP-4 inhibitors used in diabetes?
    • Sitagliptin
    • Saxagliptin
  7. What is the expected A1c reduction from DPP-4 inhibitors?
    • Sitagliptin 0.6-1.4%
    • Saxagliptin 0.4-1%
  8. What are the TZDs used in diabetes (PPAR agonists)?
    • Rosiglitazone
    • Pioglitazone
  9. What is the expected A1c reduction from DPP-4 inhibitors?
    • Rosiglitazone 0.1-0.9%
    • Pioglitazone 0.3-1.9%
  10. What are the Alpha-glucosidase inhibitors used in diabetes?
    • Miglitol
    • Acarbose
  11. What is the expected A1c reduction from Alpha-glucosidase inhibitors?
    • Miglitol 0.22-0.84%
    • Acarbose 0.56-0.7%
  12. What is the place in therapy for Metformin in diabetes?
    • 1st line
    • Wt neutral or negative
    • Monotherapy or combination therapy
    • Decreases FBG
    • Decreases TG and LDL slightly
    • Increases HDL slightly
    • Pregnancy category B
    • Has other uses; don't assume pt is diabetic
  13. What is the place in therapy for Sulfonylureas in diabetes?
    • Monotherapy or combination therapy
    • Decrease FBG
    • Relatively rapid glucose lowering
    • Work best in non-obese pts and younger pts (40-65yo or recent dx)
    • Not for those on > 40 units/d of insulin
    • Less than 5yr diabetes hx
    • Don't work very well if A1c is really high
  14. What is the place in therapy for Meglitinides in diabetes?
    • Combination therapy
    • Decrease PPG (short onset of action and short half-life)
    • Does not supply basal insulin
    • Pregnancy category C
  15. What is the place in therapy for DPP-4 inhibitors in diabetes?
    • Monotherapy or combination therapy
    • Wt neutral
    • Pregnancy category B
  16. What is the place in therapy for TZDs in diabetes?
    • Monotherapy or combination therapy
    • Metabolic syndrome or non-alcoholic fatty liver disease
  17. What is the place in therapy for Alpha-glucosidase inhibitors in diabetes?
    • Monotherapy or combination therapy
    • Decrease PPG
    • GI SE may limit use
  18. What are the patient-specific factors that affect oral antidiabetic drug selection?
    • All are CI with DKA or Type I diabetes
    • Renal dysfunction (Metformin > 1.4 in women and > 1.5 in men, Sulfonylureas, adjust DPP-4 inhibitors, Alpha-glucosidase inhibitors > 2)
    • Hepatic dysfunction (Metformin, Sulfonylureas, TZDs, Alpha-glucosidase inhibitors)
    • Hx of acidosis (Metformin)
    • Pregnancy (Sulfonylureas, Meglitinides, Alpha-glucosidase inhibitors)
    • Duration of dx (Sulfonylureas < 5y)
    • Insulin (Sulfonylureas < 40 units/d)
    • CHF (TZDs)
    • HTN (TZDs)
    • IBD (alpha-glucosidase inhibitors)
  19. Which oral antidiabetics cause wt gain?
    • Sulfonylureas
    • TZDs
  20. What is the Tier 1 progression of treatment with oral meds in diabetes?
    • Lifestyle + Metformin
    • Add basal insulin OR Sulfonylurea
    • Add bolus insulin
  21. What is the Tier 2 progression of treatment with oral meds in diabetes?
    • Lifestyle + Metformin
    • Add Pioglitazone OR GLP-1 agonist
    • Change added med to Sulfonylurea OR basal insulin
    • Add bolus insulin
  22. What is the normal dose for Metformin in diabetes?
    • 500mg BID to TID (may be titrated up to 1000mg)
    • 500mg QD ER (may be titrated up to 1000mg)
  23. What is the normal dose of sulfonylureas in diabetes?
    • Glyburide 1.25-10mg QD or BID
    • Glipizide 2.5-20mg QD or BID
    • Glimeperide 1-8mg QD
  24. What is the normal dose of Meglitinides in diabetes?
    • Repaglinide 0.5-1mg (16mg max)
    • Nateglinide 60-120mg (360mg max)
  25. What is the normal dose of DPP-4 inhibitors in diabetes?
    • Sitagliptin 25-100mg QD
    • Saxagliptin 2.5-5mg QD
  26. What is the normal dose of TZDs in diabetes?
    • Rosiglitazone 2-8mg QD or BID
    • Pioglitazone 15-45mg QD
  27. What is the normal dose of Alpha-glucosidase inhibitors in diabetes?
    • 25mg for 2 weeks
    • 25mg BID weeks 3-4
    • 25mg TID weeks 5-12
    • then 50-100mg TID
  28. How should Metformin be monitored?
    • FBG
    • A1c q 3mo until controlled, then q 6mo
    • Renal fx baseline and q 6mo
  29. How should sulfonylureas be monitored?
    • FBG
    • A1c q 3mo until controlled, then q 6mo
    • Renal fx periodically
  30. How should meglitinides be monitored?
    • FBG
    • A1c q 3mo until controlled, then q 6mo
  31. How should DPP-4 inhibitors be monitored?
    • FBG
    • A1c q 3mo until controlled, then q 6mo
    • Renal fx annually
  32. How should TZDs be monitored?
    • FBG
    • A1c q 3mo until controlled, then q 6mo
    • LFTs baseline, then q 3-6mo for first yr, then yearly
  33. How should alpha-glucosidase inhibitors be monitored?
    • FBG
    • PPG
    • Hypoglycemia sx
    • A1c q 3mo until controlled, then q 6mo
    • LFTs periodically
  34. What are the SE and DI of Metformin?
    • SE:
    • NVD (take with food, titrate slowly, XR formulation better)
    • Wt loss
    • Bloating
    • Metallic taste
    • Lactic acidosis
    • Malabsorption of B12 and Folic acid
    • CI:
    • Radio contrast dye
  35. What are the SE and DI of sulfonylureas?
    • Hypoglycemia
    • Wt Gain
    • Rash (still can use in Sulfa allergy)
    • NV (take with food)
  36. What are the SE and DI of Meglitinides?
    • NV (take with food)
    • Hypoglycemia (better than Sulfonylureas)
    • Gemfibrozil
    • 3A4 inhibitors/inducers
    • Highly protein-bound drugs (Phenytoin, Furosemide, Metformin)
  37. What are the SE and DI of DPP-4 inhibitors?
    • Hypoglycemia (decrease sulfonylureas or meglitinides if used in combination)
    • URT infection
    • Pancreatitis (Sitagliptin)
  38. What are the SE and DI of TZDs?
    • Wt gain
    • Edema - increast risk of ischemic heart disease
    • Increase fracture risk
    • Increase LDL
    • Increase HDL
    • Decrease TG (Pioglitazone only)
    • Hepatotoxicity
  39. What are the SE and DI of alpha-glucosidase inhibitors?
    • Explosive flatulence, diarrhea, abdominal pain (improves with time; titrate slowly)
    • Elevated liver enzymes (esp at high doses > 300mg/d)
    • Because of MOA, must treat hypoglycemia with Glucose, not candy or juice, etc

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