Lixisenatide is an injectable GLP-1 agonist available by the brand names of Adlyxin and Lyxumia. It is administered daily and can be used with other diabetes medications. It is also available in combination with insulin Glargine by the brand name of Soliqua.

Lixisenatide Indications:

• Diabetes mellitus Type 2:

  • Treatment of type 2 diabetes mellitus (noninsulin dependent, NIDDM) to improve glycemic control in adult patients as an adjunct to diet and exercise

Lixisenatide Dose in Adults:

Lixisenatide Dose in the treatment of Type 2 Diabetes Mellitus:

• 10 mcg SubQ once daily for 14 days (starting dose)
• Increase the dose to 20 mcg once a day on day 15 onwards.
• The usual maintenance dose is 20 mcg once a day.

Missed dose:

• If a dose is missed, it should be administered within one hour of the next meal.

Lixisenatide Use in Children:

The safety and efficacy of the drug in children have not been established.

Lixisenatide Pregnancy Risk Category: N (Not classified)

• Poor diabetes control can lead to adverse maternal and fetal outcomes, including preeclampsia and preterm births, preterm deliveries, complications during delivery, major birth defects, stillbirths, and macrosomia.
• Patients with diabetes who plan to get pregnant should maintain a strict glycemic level without hypoglycemia.
• However, lixisenatide is not recommended for use in pregnancy.

Use while breastfeeding

• It is unknown if the drug will be excreted into breastmilk.
• Manufacturer suggests weighing the risks and benefits of treatment for the mother against the potential harm to the infant.

Lixisenatide Dose in Renal Disease:

• eGFR >=30 - 89 mL/minute/1.73m2

  • These patients do not require dose adjustment.
  • Patients should be closely monitored for GI-related adverse reactions, dehydration, or worsening renal dysfunction.

• eGFR 15-29 mL/minute/1.73m2

  • These patients have not received any dose adjustments from the manufacturer.
  • As these patients are more susceptible to drug exposure, it may be necessary to adjust the dose.
  • Patients should be closely monitored for GI-related adverse reactions, dehydration, or worsening renal dysfunction.

• eGFR = 15mL/minute/1.73m2

  • This drug has not been tested in these patients, and should be avoided.

Lixisenatide Dose in Liver Disease:

• The manufacturer has not made any adjustments to the dose for patients with liver disease.
• Hepatic impairment does not require dosage adjustment, as the drug's pharmacokinetics are not affected by liver impairment.

Common Side Effects of Lixisenatide Include:

• Gastrointestinal:

  • Gastrointestinal symptoms
  • Nausea

• Immunologic:

  • Antibody development

Less Common Side Effects of Lixisenatide:

• Central nervous system:

  • Headache
  • Dizziness

• Gastrointestinal:

  • Vomiting
  • Diarrhea
  • Constipation
  • Dyspepsia
  • Abdominal distension
  • Upper abdominal pain

• Local:

  • Injection site reaction including
    • Pain
    • Pruritus
    • Erythema

Contraindications to Lixisenatide:

• Allergy reactions to any component of the drug or the drug itself

Warnings and precautions

• Anti-lixisenatide antibodies

  • Anti-lixisenatide antibody may form over time, which may lead to an attenuated response in glycemic control, especially if the antibodies are high in titers.
  • These antibodies can lead to allergic reactions in patients who have developed them.
  • Patients with high levels of antibodies, especially those who have injection site reactions or who fail to meet their glycemic goals, should seek alternative treatment.

• Hypersensitivity

  • Allergy reactions can be severe.Anaphylaxis or angioedema may occur in patients who need immediate medical attention.
  • However, hypersensitivity to GLP-1 agonists can lead to allergic reactions. Data is not available.
  • Patients with an allergy to GLP-1 agonists in the past should be closely monitored.

• Pancreatitis

  • As with all GLP-1 agonists it is associated with increased pancreatitis risk, including necrotizing and hemorhagic pancreatitis. This can be fatal.
  • Acute pancreatitis symptoms (e.g.Upper abdominal pain radiating down to the back, nausea and vomiting.
  • Patients with pancreatitis must be told to stop taking medication and should be offered alternative treatments.
  • Patients who have had a history with pancreatitis may also be interested in alternative diabetes medications.

• Bariatric surgery

  • Dehydration
    • To avoid acute renal failure, it is important to monitor and correct post-surgical hydration.
    • Patients may experience nausea, vomiting, or diarrhea when they are given GLP-1 agonists. This can lead to dehydration.
    • After gastric bypass and sleeve-gastrectomy, nausea is more common than after gastric banding.
  • Excessive glucagon -like peptide-1:
    • Patients who have undergone bariatric surgery might not require a GLP-1 antagonist.
    • Gastric bypass and sleeve gastric surgery (but not gastric banding), increase the secretion endogenous GLP-1 hormone.Exogenous GLP-1 agonists may be administered to these patients to increase the risk for pancreatitis.

• Gastroparesis

  • It slows down gastric emptying, as with all GLP-1 receptor antagonists.
  • Patients with gastroparesis should avoid it.

• Renal impairment

  • Side effects are more likely to occur if there is a high degree of renal dysfunction.
  • Diarrhea, vomiting, and nausea can all occur in patients.
  • This could cause dehydration, which could result in an acute or chronic kidney injury.
  • Patients with mild or moderate renal dysfunction should not use it.
  • Its use in patients who have an eGFR between 15 and 30 ml/minute are not known.
  • Patients with ESRD (CrCl less than 15 ml/minute) should not use it because of the increased drug exposure.
  • During treatment, patients should have their renal function monitored regularly.

Lixisenatide: Drug Interaction

Monitor:

• Serum glucose,
• hemoglobin A1C (every 3-monthly in patients who have not achieved their glycemic targets and every 6 monthly in those who have a good glycemic control)
• Renal function,
• Clinical features of pancreatitis
• Observe for GI side effects like diarrhea, nausea, and vomiting
• Observe for evidence of any allergic reactions.

How to administer Lixisenatide?

• It is administered SubQ like insulin in the anterior abdomen, a few centimeters from the umbilicus.
• Rotate the site of injection and avoid administering to infected or bruised skin.
• Before you administer the solution, ensure that it is crystal clear. It is best to take it at least one hour before your first meal of the day.

Mechanism of action of Lixisenatide:

• It acts on the same receptors that the endogenous Incretin receptors.
• It is a selective GLP-1 receptor agonist. It activates the GLP-1 receptors and causes glucose-dependent insulin release, inhibits glucagon secretion, and slows down gastric emptying.

Metabolism: It undergoes degradation by proteolytic enzymes.

Half-life elimination is about 3 hours

The time to reach the peak serum concentration is about 1 to 3.5 hours

Excretion: It is excreted in the Urine.

International Brands of Lixisenatide:

• Adlyxin
• Adlyxin Starter Pack
• Lyxumia

Lixisenatide and Insulin Glargine Brand Names:

• Soliqua

Lixisenatide Brand Names in Pakistan:

No Brands Available in Pakistan.