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 (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. 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
  6. 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] (or open in [QxMD Read])

X. 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

Images: Related links to external sites (from Google)

Cost: Medications

Byetta 5 MCG Pen (on 2/9/2012 at DrugStore.com)
Byetta 5 MCG Pen 5mcg/0.02ml Solution 1.2ml Pen #1 for $337.00 ($337.00/unit)
Byetta 10 MCG Pen (on 2/9/2012 at DrugStore.com)
Byetta 10 MCG Pen 10mcg/0.04ml Solution 2.4ml Pen #1 for $281.98 ($281.98/unit)
Victoza (on 2/9/2012 at DrugStore.com)
Victoza 18mg/3ml Solution 1 Box Contains Two 3ml Pens #1 for $325.98 ($325.98/unit)
Victoza 18mg/3ml Solution 1 Box Contains Three 3ml Pens #1 for $462.99 ($462.99/unit)

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 Glucagon-Like I, Peptídeo I Semelhante ao Glucagon, Peptídeo Semelhante ao Glucagon I, Peptídeo Glucagonóide 1, Peptídeo I Similar ao Glucagon, Peptídeo 1 Glucagonóide, Peptídeo Semelhante ao Glucagon 1, Peptídeo Similar ao Glucagon 1, Peptídeo Similar ao Glucagon I, Peptídeo 1 Similar ao Glucagon, Peptídeo 1 Semelhante ao Glucagón, Peptídeo Glucagon-Like 1
Spanish Péptido Glucagonoide 1, Peptido 1 Similar al Glucagon, Peptido Glucagonoide 1, Peptido Similar al Glucagon 1, Péptido Similar al Glucagón 1, Péptido 1 Similar al Glucagón, GLP - 1, péptido I similar al glucagón (sustancia), péptido I similar al glucagón, Peptido 1 Glucagonoide, Péptido 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
Finnish Glukagonia muistuttava peptidi 1
French Glucagon-like peptide I, GLP-1, Glucagon-like peptide 1, Glucagon-like peptide-1, Proglucagon (78-107)
Polish Peptyd glukagonopodobny 1

Ontology: exenatide (C0167117)

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