Incretin Mimetic

Aka: Incretin Mimetic, Byetta, Exenatide, Bydureon, Liraglutide, Victoza, GLP-1 Analog, Glucagon-Like Peptide 1, GLP-1

1. See Also
   1. Sitagliptin (Januvia)
   2. Dipeptidyl Peptidase-4 Inhibitor (DPP-4 Inhibitor)
2. Indications
   1. Type II Diabetes Mellitus
      1. Especially in Obesity
      2. May be used in combination with basal Insulin (e.g. Lantus)
   2. Insulin deficiency and Insulin Resistance
      1. Adjunct to Glucophage, Sulfonylureas, Glitazones
3. Contraindications
   1. Type I Diabetes Mellitus
   2. Concurrent prandial Insulin (bolus Insulin)
      1. Basal Insulin (e.g. Lantus) may be used with Byetta
   3. Renal Failure: Creatinine Clearance <30 ml/min
4. Mechanism
   1. Synthetic form of exendin-4
      1. Originally identified in Gila Monster Saliva
      2. Peptide with 39 amino acids
   2. Incretin Mimetic
      1. Incretin analogue that mimics endogenous hormone
      2. Incretin released from GI tract following meals
   3. Incretin effects
      1. Increases Glucose dependent Insulin secretion
      2. Delays gastric emptying
      3. Decreases food intake (improves satiety)
5. Preparations
   1. Exenatide (Byetta)
      1. Glucagon-Like Peptide 1 (GLP-1) agonist derived from Gila monster Saliva
      2. Associated with weight loss and Nausea
   2. Exenatide Weekly (Bydureon)
      1. Injected once weekly
      2. More effective than Byetta and as effectiev as Victoza
      3. Less Nausea than Byetta or Victoza
      4. Requires reconstitution from powder before dose
   3. Liraglutide (Victoza)
      1. Single daily injection (as contrasted with twice daily Byetta)
      2. More potent than Byetta in lowering Hemoglobin A1C and similar efficacy to
      3. Adverse effects include Nausea (transient) and Headache
6. Dosing: Byetta
   1. Initial
      1. Byetta 5 mcg SQ twice daily
      2. Give within 60 minutes of morning and evening meals
   2. Later, if Blood Sugars not optimized
      1. May increase to 10 mcg bid after 1 month
   3. Preparations: Prefilled pen holds 30 day supply
      1. 5 mcg/dose pen holds 1.2 ml of 250 mcg/ml
      2. 10 mcg/dose pen holds 2.4 ml of 250 mcg/ml
7. Efficacy
   1. Lowers HBA1C 0.4 to 0.8% (at 5 and 10 mcg doses)
   2. Lowers weight by up to 4-10 pounds
8. Cost
   1. Monthly: $340 per month
9. Adverse effects: Byetta
   1. Nausea (44%) or Vomiting (13%)
      1. Less frequent with Bydureon
   2. Diarrhea (13%)
   3. Dizziness (9%)
   4. Headache (9%)
   5. Hypoglycemia
      1. With Sulfonylurea: 14.4% at 5 mcg, 35.7% at 10 mcg
      2. With Glucophage: 4.5% at 5 mcg, 5.3% at 10 mcg
   6. Pancreatitis
      1. Incidence may be as high as 1 in 50 on Byetta for two years
      2. Singh (2013) JAMA Intern Med 173(7):534-9
10. Precautions
    1. Avoid using 2 Incretins (e.g. Byetta with Januvia) in combination (raises cost, risk of Pancreatitis without significant benefit)
    2. (2012) Presc Lett 19(8): 45
11. References
    1. (2012) Presc Lett 19(3): 15
    2. Dungan (2005) Clin Diabetes 23: 56-62
    3. Ezzo (2006) Am Fam Physician 73
    4. Fineman (2003) Diabetes Care 26:2370-7
    5. Jones (2007) Am Fam Physician 75:1831-5
    6. Joy (2005) Ann Pharmacol 39:110-8