II. 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

III. 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

IV. 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)

V. Preparations

  1. General selection
    1. All agents are expensive ($300 to $600 per month)
    2. The most potent agents (Exenatide ER, Dulaglutide, Liraglutide) lower Hemoglobin A1C 1.5%
    3. The most weight loss (6 pounds) occurs with Exenatide ER, Dulaglutide, Liraglutide
    4. Once weekly dosing is available for Albiglutide, Exenatide ER and Dulaglutide
    5. Most difficult to prepare are Exenatide ER and Albiglutide which both require reconstitution before injection
    6. Dulaglutide and Liraglutide appear to be most potent with greatest weight loss, weekly dosing and easiest to prepare
  2. Exenatide (Byetta)
    1. Glucagon-Like Peptide 1 (GLP-1) agonist derived from Gila monster Saliva
    2. Associated with weight loss and Nausea
    3. Lowers Hemoglobin A1C by 1.0%
  3. Exenatide ER Weekly (Bydureon)
    1. Injected once weekly
    2. More potent than Byetta (lowers Hemoglobin A1C by 1.3%)
    3. Less Nausea than Byetta or Victoza
    4. Requires reconstitution from powder before dose
    5. Less Nausea than Byetta and Victoza
    6. More injection site reactions than Byetta and Victoza
  4. Liraglutide Standard Dose (Victoza)
    1. Single daily injection (as contrasted with twice daily Byetta)
    2. More potent than Byetta (lowers Hemoglobin A1C by 1.5%)
    3. Adverse effects include Nausea (transient) and Headache
  5. Liraglutide High Dose (Saxenda)
    1. Saxenda is dosed up to 3 mg daily (contrast with 1.8 mg with Victoza)
    2. FDA approved as an Obesity Medication with release in 2015
    3. Associated with gastrointestinal side effects (Nausea, Vomiting and Diarrhea)
    4. Consider in Type II Diabetes Mellitus in which an Obesity Medication is being considered
  6. Albiglutide (Tanzeum)
    1. Similar potency to Byetta (lowers Hemoglobin A1C by 1.0%)
    2. Less weight loss than with other agents (1-2 pounds compared with 6 pounds with other agents)
    3. Injected once weekly (similar to Bydureon)
    4. Less Nausea than Byetta and Victoza
    5. More injection site reactions than Byetta and Victoza
  7. Dulaglutide (Trulicity)
    1. Newer agent of the class (released in 2014)
    2. More potent than Byetta (lowers Hemoglobin A1C by 1.5%)
    3. Once weekly injection
    4. Weight loss of 6 pounds on average

VI. 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

VII. Efficacy

  1. Lowers HBA1C 0.4 to 0.8% (at 5 and 10 mcg doses)
  2. Lowers weight by up to 4-10 pounds

VIII. Cost

  1. Tanzeum: $325/month
  2. Bydureon: $400+/month
  3. Byetta: $400+/month
  4. Victoza: $600/month

IX. 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 (occurs with all GLP-1 Agonists)
    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 [PubMed]

X. Precautions

  1. Avoid using 2 Incretins (e.g. Byetta with Januvia) in combination (raises cost, risk of Pancreatitis without significant benefit)
    1. (2012) Presc Lett 19(8): 45

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Cost: Medications

byetta (on 1/1/2015 at Medicaid.Gov Survey of pharmacy drug pricing)
BYETTA 10 MCG DOSE PEN INJ $195.11 per ml
BYETTA 5 MCG DOSE PEN INJ $386.24 per ml
bydureon (on 1/1/2015 at Medicaid.Gov Survey of pharmacy drug pricing)
BYDUREON 2 MG PEN INJECT $114.77 each
BYDUREON 2 MG VIAL $115.71 each
victoza (on 7/1/2014 at Medicaid.Gov Survey of pharmacy drug pricing)
VICTOZA 2-PAK 18 MG/3 ML PEN $63.48 per ml
VICTOZA 3-PAK 18 MG/3 ML PEN $63.24 per ml
tanzeum (on 1/21/2015 at Medicaid.Gov Survey of pharmacy drug pricing)
TANZEUM 30 MG PEN INJECT $78.52 each

Ontology: Glucagon-Like Peptide 1 (C0061355)

Definition (MSH) A peptide of 36 or 37 amino acids that is derived from PROGLUCAGON and mainly produced by the INTESTINAL L CELLS. GLP-1(1-37 or 1-36) is further N-terminally truncated resulting in GLP-1(7-37) or GLP-1-(7-36) which can be amidated. These GLP-1 peptides are known to enhance glucose-dependent INSULIN release, suppress GLUCAGON release and gastric emptying, lower BLOOD GLUCOSE, and reduce food intake.
Concepts Amino Acid, Peptide, or Protein (T116)
MSH D052216
SnomedCT 43004008
Portuguese Peptídeo 1 Semelhante ao Glucagon, Peptídeo 1 Similar ao Glucagon, Peptídeo I Semelhante ao Glucagon, Peptídeo Semelhante ao Glucagon 1, Peptídeo Similar ao Glucagon 1, Peptídeo Glucagonoide 1, Peptídeo I Similar ao Glucagon, Peptídeo Semelhante ao Glucagon I, Peptídeo Glucagon-Like I, Peptídeo Glucagon-Like 1, Peptídeo Similar ao Glucagon I, Peptídeo 1 Glucagonoide
Italian Peptide 1 simile al glucagone, GLP-1
German Glucagon-Like-Peptide-1, Glucagon-ähnliches Peptid 1, GLP-1, Glukagon-ähnliches Peptid 1
Swedish Glucagonliknande peptid 1
English GLP1, GLUCAGON-LIKE PEPTIDE 1, Glucagon-Like Peptide 1, GLUCAGON LIKE PEPTIDE 001, Glucagon-Like Peptide 1 [Chemical/Ingredient], glp-1, glp 1, glucagon like peptide 1, Glucagon-like peptide 1, Glucagon-like peptide 1 (substance), GLP-1, GLP 1, Glucagon Like Peptide 1, Glucagon-Like Peptide-1
Czech GLP-1, peptid 1 podobný glukagonu, glukagonu podobný peptid 1
Spanish Péptido 1 Similar al Glucagón, Péptido 1 Glucagonoide, Péptido Similar al Glucagón 1, Péptido Glucagonoide 1, GLP - 1, péptido I similar al glucagón (sustancia), péptido I similar al glucagón
Finnish Glukagonia muistuttava peptidi 1
French Glucagon-like peptide I, GLP-1, Glucagon-like peptide 1, Glucagon-like peptide-1, Proglucagon (78-107)
Russian GLIUKAGON-PODOBNYI PEPTID 1, ГЛЮКАГОН-ПОДОБНЫЙ ПЕПТИД 1
Polish Peptyd glukagonopodobny 1
Norwegian Glukagonlignende peptid 1, GLP-1

Ontology: exenatide (C0167117)

Definition (NCI) A 39 amino acid peptide and synthetic version of exendin-4, a hormone found in the saliva of the venomous lizard Gila monster, with insulin secretagogue and antihyperglycemic activity. Exenatide is administered subcutaneously and mimics human glucagon-like peptide-1 (GLP-1). Compared to GLP-1, exenatide has a longer half-life of 2.4 hours.
Concepts Amino Acid, Peptide, or Protein (T116) , Pharmacologic Substance (T121)
MSH C074031
SnomedCT 416859008, 417734003
English exendin-4, EXENATIDE, exenatide (medication), exenatide [Chemical/Ingredient], Ex4 peptide, exendin 4, exenatide, Exendin 4, Exenatide (product), Exenatide (substance), Exenatide
Spanish exenatida (producto), exenatida (sustancia), exenatida

Ontology: Byetta (C1636686)

Concepts Amino Acid, Peptide, or Protein (T116) , Pharmacologic Substance (T121)
MSH C074031
English Byetta