Exenatide (Byetta, Bydureon), a GLP-1 (Glucagon-like peptide 1) analogue, boosts insulin secretion while lowering the pancreas' overactive glucagon release.

Exenatide (Byetta, Bydureon) Uses:

• Diabetes mellitus Type 2:

  • In addition to diet and exercise, treatment for type 2 diabetes mellitus aims to enhance glycemic control.

Other GLP-1 analogs include:

• Liraglutide (Victoza)
• Dulaglutide (Trulicity)
• Semaglutide (Ozempic and Rybelsus)

Exenatide (Byetta, Bydureon) Dose in Adults

Exenatide (Byetta, Bydureon) Dose in the treatment of type 2 Diabetes mellitus: SubQ:

• Immediate-release:

  • Initial: 5 mcg twice day, one hour before breakfast and dinner (or before the two main meals of the day, roughly six hours apart); after a few days
  • The dose may be increased to 10 mcg twice daily (depending on response).

• Missed dose:

  • If a dose is missed, continue the treatment plan as directed with the following scheduled dose.

• Extended-release:

  • 2 mg, once per week, with or without meals, at any time of the day.

• Missed dose:

  • If the next regularly scheduled dose is due in three days or more, you can administer the missing dose as soon as you realise it.  After that, your schedule will resume as usual.
  • Do not administer the missing dose; instead, resume treatment with the next regularly scheduled dose if a dose is missed and the  next one is due one or two days from now.
  • Wait three days or longer after the prior dose was administered before administering the subsequent dose in order to establish a  new day of the week dosing regimen.

• Conversion  to ER:

  • The day after stopping exenatide immediate release, start weekly exenatide administration.
  • Note:
    • Blood glucose levels may rise for two to four weeks following conversion.
    • When starting ER exenatide, immediate-release exenatide is not necessary as a pretreatment.

Use in Children:

Not indicated.

Exenatide (Byetta, Bydureon) Pregnancy Risk Category: C

• Women with diabetes who experience maternal hyperglycemia run the risk of congenital abnormalities as well as negative effects on the foetus,  newborn, and mother.
• Exenatide's potential to cross the placenta is low based on in vitro data.
• Preventing adverse outcomes by keeping maternal blood glucose and HbA as close as possible to the target levels during pregnancy and before conception.
• However, it is important to avoid significant hypoglycemia.
• Pregnant women with diabetes should be treated with medications other than exenatide.

Breastfeeding:

• Exenatide may be present in breastmilk, but it is unknown.
• According to the manufacturer breastfeeding during therapy is a decision that should be made after considering the risks to infants and the benefits to mothers.

Exenatide (Byetta, Bydureon) Dose in Kidney Disease:

• Instant-release

  • CrCl >=30mL/minute
    • There is no dosage adjustment; patients with CrCl 30-50 mL/minute should be cautious when initiating therapy. Monitor for hypovolemia.
  • CrCl 30mL/minute
    • It is not advised.
  • ESRD:
    • It is not advised.

• Extended-release

  • eGFR >=45mL/minute/1.73m2
    • There is no need to adjust the dosage.
    • Be cautious and monitor for hypovolemia.
  • eGFR = 45 mL/minute/1.73m2
    • It is not advised.
  • ESRD:
    • Not advised.

Exenatide (Byetta, Bydureon) Dose for Liver disease:

• No dosage modifications are mentioned on the manufacturer's label (has not yet been studied).
• However, it is unlikely that exenatide pharmacokinetics will be affected by hepatic dysfunction.

Unless stated, incidence rates refer to the extended-release formulation.

Common Side Effects of Exenatide (Byetta, Bydureon):

• Gastrointestinal:

  • Nausea
  • Diarrhea

• Immunologic:

  • Immunogenicity

• Local:

  • Injection Site Reaction
  • Injection Site Nodule

Less Common Side Effects Of Exenatide (Byetta, Bydureon):

• Central Nervous System:

  • Headache
  • Dizziness

• Dermatologic:

  • Injection Site Pruritus

• Endocrine & Metabolic:

  • Hypoglycemia
  • Severe Hypoglycemia

• Gastrointestinal:

  • Constipation
  • Vomiting
  • Dyspepsia
  • Decreased Appetite

• Immunologic:

  • Antibody Development

• Local:

  • Erythema At Injection Site

Rare Side effects:

• Cardiovascular:

  • Increased heart rate

Contraindications to Exenatide (Byetta, Bydureon):

• Severe reaction to exenatide and any formulation ingredient in the past
• A history of medullary carcinoma in the family or one's own (exenatide-ER only)
• Individuals with type 2 numerous endocrine diseases (exenatide-ER only)

Labeling in Canada: Additional warnings not included in US labelling

• Byetta
  • Diabetic ketoacidosis
  • Type 1 diabetes mellitus or diabetic coma/precoma
  • Severe renal impairment (CRCl 30 mL/min for dialysis patients) or end-stage renal disease (ESRD)
• Bydureon
  • Dialysis patients who have end-stage renal disease (ESRD) or severe renal impairment (CrCl 30 mL/minute) are included.

Warnings and precautions

• Anti-exenatide antibodies

  • Low titers do not cause a loss in efficacy. However, high titers may lead to an attenuation in response (observed in 6-12% of patients in clinical trials).
  • This may lead to the formation of anti-exenatide antibody.

• Hypersensitivity

  • Serious injection-site responses, such as cellulitis, necrosis, and abscess, have been linked to using the product.
  • Anaphylaxis and gioedema are two severe hypersensitivity events that have been reported. If this occurs, stop the therapy.
  • Surgery is only necessary in rare instances.

• Gallbladder disease

  • Gallbladder examinations, cholecystitis, and cholelithiasis cases have all been reported. Further clinical evaluation and gallbladder  tests are advised if cholelithiasis is suspected.

• GI symptoms

  • GI-related responses are the most typical. These side effects might be dose-related.  With continuous use and moderate titration, they might become less severe.

• Pancreatitis

  • Pancreatitis (acute) has been described in cases of hemorhagic or necrotizing pancreatitis with some fatalities.
  • Keep an eye out for symptoms including chronic stomach pain that radiates to the back and vomiting.
  • Be knowledgeable of additional risks that could result in pancreatitis before beginning treatment (eg, hypertriglyceridemia or cholelithiasis).
  • Exenatide may put these people at higher risk for pancreatitis, but this is unknown.When you suspect pancreatitis, stop using.
  • Do not resume if you are unsure.
  • Alternative anti-diabetic treatments should be considered by patients with a history of pancreatitis.

• Effects on the renal system:

  • There have been instances of acute renal failure and chronic renal failure aggravation, with severe cases necessitating  hemodialysis or transplantation.
  • Animal studies have demonstrated that exenatide-ER causes thyroid C-cell tumours. The medicine may produce thyroid C-cell tumours in people, however this is uncertain.
  • With the right corrective measures, such as discontinuing exenatide, renal dysfunction can usually be reversed.
  • Patients who are taking concomitant medications that affect renal function or hydration may be at greater risk.
  • It can cause nausea/vomiting/diarrhea and transient hypovolemia, which can lead to deterioration of renal function.

• Thyroid tumors: Bydureon [US Boxed Warning]

  • Exenatide should be talked with patients in order to go over potential MTC risks and thyroid cancer symptoms (eg neck mass,  dysphagia persistent hoarseness, dysphagia)
  • An endocrinologist should be consulted by patients who have thyroid nodules or increased calcitonin levels that were found during  imaging tests or physical examinations.
  • Patients with a history of medullary cancer or multiple endocrine neplasia types 2 (MEN2) are not advised to use exenatide ER.
  • It is advised to regularly check serum calcium levels and use thyroid ultrasonography to look for early indications of MTC.
  • Human MTC has been linked to the GLP-1 agonist Liraglutide.

• GI disease:

  • Patients with severe GI diseases or gastroparesis should not use this product because of the frequent GI adverse reactions.

• Renal impairment

  • Exenatide ER or end stage renal disease (ESRD) patients or those with CrCl levels  less than 30 mL/min or 45 mL/min should not use this medication.
  • It is used to monitor hypovolemia in transplant patients.

Exenatide: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Serum glucose
• Renal function
• Volume status
• Signs and symptoms of pancreatitis
• Weight
• Triglycerides
• Gallbladder disease symptoms

How to administer Exenatide (Byetta, Bydureon)?

• SubQ
  • SubQ injections are administered in the abdomen, upper arm, and thighs. Rotate injection sites.
  • Concomitant insulin use should be administered as separate injections. You may inject insulin in the same area as insulin but not next to each other.
  • Don't inject IV or IM.
  Instant-release
  • Use only if the solution is crystal clear, colourless, devoid of impurities, and not hazy.
  • Take the drug an hour before your main daily meals, either in the morning or evening.
  • Before you use a new pen, make sure to prim it.
  • For more information, refer to the pen manual.
  • In the dosage window, dial the dose before each delivery.
  Extended-release
  • Can be given at any time of day or without consideration to meals.
  Single-dose Bydureon tray:

  • After reconstitution in a diluent, give a dose right away. It should be clear to slightly hazy and white.

  • The single-dose tray's other components cannot be replaced with needles.

  Bydureon Pen
  • Allow the pen to warm up to room temperature before use (wait at minimum 15 minutes after removing from the fridge).
  • For mixing, hold the orange label at the end of your pen and tap the palm of your hand hard. It may take up to 80 taps to get the mixture just right.
  • The suspension ought to appear evenly blended, opaque, and white or off-white.
  • Mixture immediately.
  • After inserting the needle, press the button to ensure that it clicks. Hold for 10 seconds.
  Autoinjector Bydureon BCise:
  • Allow the autoinjector temperature to reach room temperature before using.
  • For 15 seconds, shake the auto-injector vigorously. The suspension should look opaque to off-white.
  • Mixture immediately.
  • For maximum delivery, hold the autoinjector on the skin for 15 seconds.

Mechanism of action of Exenatide (Byetta, Bydureon):

• Exenatide (glucagon-like progesterone 1, or GLP-1), an analogue of the incretin hormone, boosts glucose dependent insulin, reduces unneeded glucagon release, and promotes B-cell proliferation and replication.
• It also decreases food intake and slows down stomach emptying.
• A 0.5% to 1% (immediate release) and a 1.5% to 1.9% decrease in haemoglobin A levels will occur (1 extended-release).

Metabolism:

• Systemic metabolism is minimal;
• After glomerular filtration, proteolytic degrading may occur

Eliminating half-life:

• Instant release (daily formulation): 2.4 Hours
• Extended-release (weekly formulation):2 Weeks

When SubQ is administered, time to reach peak plasma concentration:

• Instant release (daily formulation)2.1 hours
• Extended-release (weekly formulation):
  • One-time use:

    • Microspheres gradually release surface-bound excenatide after the first release.  Peaks happen in weeks 2 (and six to seven, respectively).

    • Once-weekly dose results in a steady state at 6 to 7 (Bydureon BCise) or 10 hours (Bydureon BCIse).

Excretion:

• Urine (majority dose)

International Brand Names of Exenatide:

• Byetta 5 MCG Pen
• Baietta
• Byetta
• Bydureon
• Bydureon BCise
• Byetta 10 MCG Pen

Exenatide Brand Names in Pakistan:

No Brands Available in Pakistan.