Exenatide

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Contents

[edit] BRAND NAMES

[edit] STRUCTURE

Exenatide.jpg

[edit] MECHANISM OF ACTION

Type 2 diabetes is a disease in which the pancreas does not make enough insulin to control the level of glucose in the blood or when the body is unable to use insulin effectively.

Incretins, such as glucagon-like peptide-1 (GLP-1), enhance glucose-dependent insulin secretion and exhibit other antihyperglycemic actions following their release into the circulation from the gut.

Exenatide is structurally similar to the native glucagon-like peptide (incretin mimetic). It acts as a GLP-1 receptor agonist and improves glycemic control by reducing fasting and postprandial glucose concentrations in patients with type 2 diabetes:

  • Exenatide Enhances glucose-dependent insulin secretion by the pancreatic beta-cell.
  • Exenatide Suppresses inappropriately elevated glucagon secretion which is known to be inappropriately elevated in type 2 diabetes. Lower glucagon concentrations lead to decreased hepatic glucose output. However, exenatide does not impair the normal glucagon response and other hormone responses to hypoglycemia.
  • Exenatide Slows gastric emptying thereby reducing the rate at which meal-derived glucose appears in the circulation.

[edit] INDICATIONS

Exenatide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Exenatide is not a substitute for insulin. Exenatide should not be used for the treatment of type 1 diabetes or diabetic ketoacidosis.

Concurrent use with prandial insulin has not been studied and cannot be recommended.

[edit] DOSAGE

  • Exenatide (Byetta): Inject subcutaneously within 60 minutes prior to morning and evening meals (or before the two main meals of the day, approximately 6 hours or more apart). Initiate at 5 mcg per dose twice daily; increase to 10 mcg twice daily after 1 month based on clinical response.
  • Exenatide extended-release (Bydureon): Administer 2 mg by subcutaneous injection once every seven days (weekly), at any time of day and with or without meals. Administer immediately after the powder is suspended

[edit] DOSAGE FORMS AND STRENGTHS

  • BYETTA is supplied as 250 mcg/mL exenatide in:
    • 5 mcg per dose, 60 doses, 1.2 mL prefilled pen
    • 10 mcg per dose, 60 doses, 2.4 mL prefilled pen
  • BYDUREON is 2 mg exenatide for extended-release injectable suspension.

[edit] CONTRAINDICATIONS

  • History of severe hypersensitivity to exenatide or any product components
  • Patients with severe renal impairment (creatinine clearance < 30 mL/min) or end-stage renal disease.
  • Exenatide extended-release (Bydureon): Do not use if personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2.

[edit] WARNINGS AND PRECAUTIONS

  • Pancreatitis: Postmarketing reports with exenatide, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis. After initiation of exenatide, and after dose increases, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue Exenatide promptly. If pancreatitis is confirmed Exenatide should not be restarted. Consider other antidiabetic therapies in patients with a history of pancreatitis.
  • Exenatide extended-release (Bydureon): Exenatide extended-release causes thyroid C-cell tumors at clinically relevant exposures in rats. It is unknown whether Bydureon causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as human relevance could not be determined by clinical or nonclinical studies.
  • Hypoglycemia: Increased risk when Exenatide is used in combination with medications known to cause hypoglycemia [e.g. insulin or insulin secretagogues (Glibenclamide, Gliclazide, Glimepiride, Glipizide, Gliquidone)]. Consider reducing the dose of insulin or insulin secretagogue
  • Renal Impairment: Postmarketing reports with exenatide, sometimes requiring hemodialysis and kidney transplantation. Exenatide should not be used in patients with severe renal impairment or end-stage renal disease and should be used with caution in patients with renal transplantation. Caution should be applied when initiating Exenatide or escalating the dose of Exenatide in patients with moderate renal failure.
  • Severe Gastrointestinal Disease: Use of Exenatide is not recommended in patients with severe gastrointestinal disease (e.g., gastroparesis: delayed gastric emptying), because Exenatide is commonly associated with gastrointestinal adverse reactions, including nausea, vomiting, and diarrhea.
  • Hypersensitivity: Postmarketing reports with exenatide of hypersensitivity reactions (e.g. anaphylaxis and angioedema). The patient should discontinue Exenatide and other suspect medications and promptly seek medical advice.
  • Macrovascular outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Exenatide or any other antidiabetic drug

[edit] INTERACTIONS

  • The effect of Exenatide to slow gastric emptying can reduce the extent and rate of absorption of orally administered drugs. For oral medications that are dependent on threshold concentrations for efficacy, such as contraceptives and antibiotics, patients should be advised to take those drugs at least 1 hour before Exenatide injection.
  • Warfarin: Postmarketing reports of increased INR sometimes associated with bleeding. Monitor INR frequently until stable upon initiation or alteration of Exenatide therapy

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category C (US) Based on animal data, Exenatide may cause fetal harm. Exenatide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
  • Nursing Mothers: Caution should be exercised when Exenatide is administered to a nursing woman.

[edit] SIDE EFFECTS

Exenatide: Most common (≥5%) and occurring more frequently than placebo in clinical trials: nausea, hypoglycemia, vomiting, diarrhea, feeling jittery, dizziness, headache, dyspepsia, constipation, asthenia. Nausea usually decreases over time.

Postmarketing reports with exenatide of increased international normalized ratio (INR) with concomitant use of warfarin, sometimes with bleeding.


Exenatide extended-release (Bydureon): Most common adverse reactions (≥5%) and occurring more frequently than comparator in clinical trials are nausea, diarrhea, headache, vomiting, constipation, injection site pruritus, injection site nodule, and dyspepsia

[edit] RELATED LINKS

GLP-1 function - Exenatide (Byetta), Liraglutide (Victoza), Lixisenatide (Lyxumia)
Understanding Type 2 Diabetes
A simple explanation of what diabetes is

[edit] BIBLIOGRAPHY

[edit] REFERENCES

Diabetes (Antidiabetic drugs)
Insulin Secretagogues (drugs that increase insulin release from pancreas) Sulfonylureas Chlorpropamide (Diabinese)   Glibenclamide or Glyburide (Diabeta, Micronase, Glynase, Daonil, Euglycon)   Gliclazide (Diamicron)   Glimepiride (Amaryl, Solosa)   Glipizide (Glucotrol, Minidiab, Glibenese)   Gliquidone (Glurenorm)
Meglitinides Repaglinide (Prandin, Novonorm)   Nateglinide (Starlix)
Dipeptidyl peptidase-4 inhibitors Linagliptin (Trajenta)   Saxagliptin (Onglyza)   Sitagliptin (Januvia)   Vildagliptin (Galvus)
Incretin mimetics (GLP-1 agonists and analogs) Exenatide (Byetta)   Liraglutide (Victoza)   Lixisenatide (Lyxumia)   Dulaglutide (Trulicity)
Insulin Sensitizers (drugs that decrease insulin resistance)
Biguanides Metformin (Glucophage)
Thiazolidinediones Pioglitazone (Actos)
Drugs that retard the digestion and absorption of carbohydrates in the small intestine
Alpha-glucosidase inhibitors Acarbose (Glucobay, Precose)
Drugs that reduce glucose absorption in the kidney and increase glucose excretion in the urine
Sodium glucose cotransporter 2 (SGLT2) inhibitors Canagliflozin (Invokana)   Dapagliflozin (Farxiga)   Empagliflozin (Jardiance, Glyxambi, Synjardi)
Insulin and insulin analogs
Intermediate acting insulins Insulin lispro protamine (Humalog BASAL)   Isophane human insulin : Human insulin protamine (NPH) (Humulin I, Protaphane)
Long-acting insulins‎ Insulin detemir (Levemir)   Insulin glargine (Lantus)
Fast-acting insulins‎ Regular insulin : Insulin (Human recombinant) (Actrapid, Humulin R)
Ultra-rapid-acting insulins‎‎ Insulin aspart (Novorapid)   Insulin glulisine (Apidra)   Insulin lispro (Humalog)   Insulin human (Inhalation Powder) (Afrezza)
Premixed insulin‎‎‎ (ultra-rapid-acting + intermediate acting Insulin aspart / Insulin aspart protamine (Novomix)   Insulin lispro / Insulin lispro protamine (Humalog Mix)
Inhaled Insulin Insulin human (Inhalation Powder) (Afrezza)
Combination therapy
Sulfonylurea + Metformin Glibenclamide / Metformin (Bieuglicon M, Diaglimet, Glibomet, Gliconorm, Glicorest, Suguan M)
Thiazolidinedione + Metformin Pioglitazone / Metformin (Competact, Glubrava)
Thiazolidinedione + Sulfonylurea Pioglitazone / Glimepiride (Tandemact)
Dipeptidyl peptidase-4 inhibitors + Metformin Linagliptin / Metformin (Jentadueto)   Sitagliptin / Metformin (Efficib, Janumet, Velmetia)   Vildagliptin / Metformin (Eucreas)