Usage
Lixisenatide is prescribed as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is a glucagon-like peptide-1 (GLP-1) receptor agonist. It is not indicated for type 1 diabetes or diabetic ketoacidosis. As of January 1, 2023, it is no longer available in the U.S.
Alternate Names
- Generic: Lixisenatide
- Brand: Adlyxin, Lyxumia (international)
- Combination: Soliqua (with insulin glargine), Suliqua (with insulin glargine, international)
How It Works
Pharmacodynamics: Lixisenatide works by binding to and activating the GLP-1 receptor, mimicking the effects of the naturally occurring incretin hormone GLP-1. This leads to:
- Glucose-dependent insulin secretion: Lixisenatide stimulates insulin release from the pancreas primarily when blood glucose levels are elevated, minimizing the risk of hypoglycemia.
- Suppression of glucagon secretion: Glucagon, a hormone that raises blood sugar, is suppressed by lixisenatide.
- Delayed gastric emptying: This slows the rate at which food is absorbed, preventing postprandial glucose spikes.
- Increased satiety: Some patients experience a feeling of fullness, which may contribute to weight management.
Pharmacokinetics:
- Absorption: Lixisenatide is rapidly absorbed after subcutaneous injection, reaching peak plasma concentration in about 1 to 2 hours.
- Metabolism: It is likely metabolized by non-specific proteolytic degradation, meaning it’s broken down by enzymes throughout the body, not by a single specific pathway like some other medications. This is similar to how natural GLP-1 is cleared.
- Elimination: Primarily eliminated through the kidneys (glomerular filtration) and proteolytic degradation, meaning it is filtered by the kidneys and also broken down elsewhere. The terminal half-life is approximately 3 hours.
- Special Cases: In patients with mild to moderate renal impairment, pharmacokinetic parameters are similar to those with normal renal function. However, those with severe renal impairment have increased drug exposure. It hasn’t been studied in those with end-stage renal disease, and its use is generally avoided.
Dosage
Standard Dosage
Adults:
- Starting dose: 10 mcg subcutaneously once daily for 14 days.
- Maintenance dose: 20 mcg subcutaneously once daily, starting on Day 15. Administer within 1 hour before the first meal of the day.
Children:
- Lixisenatide’s safety and efficacy have not been established in pediatric patients.
Special Cases:
- Elderly Patients: No dose adjustment is necessary based on age alone, however closer monitoring is recommended.
- Patients with Renal Impairment: No dose adjustment is needed for mild to moderate impairment, but close monitoring for adverse effects is recommended. Lixisenatide is not recommended for patients with severe renal impairment (creatinine clearance < 30 mL/min) or end-stage renal disease.
- Patients with Hepatic Dysfunction: Formal studies haven’t been done in patients with hepatic impairment, but caution is advised.
- Patients with Comorbid Conditions: Use with caution in patients with a history of pancreatitis or severe gastrointestinal disease, including gastroparesis.
Clinical Use Cases Lixisenatide’s indicated use is solely for the management of type 2 diabetes. It is not indicated for use in situations like intubation, surgical procedures, mechanical ventilation, or emergency situations.
Dosage Adjustments Dose adjustments may be needed if used concurrently with a sulfonylurea or basal insulin to mitigate hypoglycemia risk.
Side Effects
Common Side Effects:
Nausea, vomiting, diarrhea, headache, dizziness, injection site reactions (pain, itching, redness)
Rare but Serious Side Effects:
- Pancreatitis (including fatal and non-fatal hemorrhagic or necrotizing pancreatitis)
- Anaphylaxis and serious hypersensitivity reactions (including angioedema)
- Severe hypoglycemia (especially when used with sulfonylureas or insulin)
- Acute renal injury
- Gallbladder disease (including cholelithiasis and cholecystitis)
Long-Term Effects Long-term side effects are not explicitly defined in the literature, but continued monitoring for the rare but serious adverse events is necessary. There is a potential for antibody formation.
Contraindications
- Known hypersensitivity to lixisenatide
- Type 1 diabetes mellitus
- Diabetic ketoacidosis
- History of pancreatitis
- Severe gastrointestinal disease (including gastroparesis)
- End-stage renal disease
- Pregnancy
Drug Interactions
Lixisenatide delays gastric emptying, potentially impacting the absorption of oral medications. Clinically significant interactions include:
- Sulfonylureas and insulin: Increased risk of hypoglycemia.
- Oral contraceptives: Take at least 1 hour before or 11 hours after lixisenatide.
- Antibiotics: Take at least 1 hour before or 4 hours after lixisenatide.
- Drugs with narrow therapeutic index: Careful monitoring required.
- Paracetamol (acetaminophen): May require timing adjustments.
- Alcohol: Affects blood sugar levels, use caution.
Pregnancy and Breastfeeding
- Pregnancy: Lixisenatide is contraindicated during pregnancy. Insulin is the recommended treatment for diabetes during pregnancy.
- Breastfeeding: It is unknown if lixisenatide is excreted in human milk. It is recommended to avoid using lixisenatide while breastfeeding.
Drug Profile Summary (Already addressed above in detail)
Popular Combinations
Lixisenatide may be used in combination with metformin, a sulfonylurea, or basal insulin. However, combined use with basal insulin and a sulfonylurea together should be avoided due to the increased risk of hypoglycemia.
Precautions (Already addressed above in detail)
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Lixisenatide?
A: The starting dose is 10 mcg subcutaneously once daily for 14 days, followed by a maintenance dose of 20 mcg subcutaneously once daily, administered within 1 hour before the first meal of the day.
Q2: How does Lixisenatide differ from other GLP-1 receptor agonists?
A: Lixisenatide is a once-daily, short-acting GLP-1 receptor agonist. Others may have different dosing frequencies (twice daily, weekly) and durations of action. Lixisenatide was not associated with an increased risk of thyroid C-cell tumors in clinical trials, unlike some other GLP-1 receptor agonists.
Q3: Can Lixisenatide be used in patients with renal impairment?
A: It can be used with caution in patients with mild to moderate renal impairment, but close monitoring is essential. It is not recommended for severe renal impairment or end-stage renal disease.
Q4: What are the most common side effects of Lixisenatide?
A: Nausea, vomiting, diarrhea, headache, and dizziness are the most common side effects.
Q5: What should patients do if they miss a dose of Lixisenatide?
A: The missed dose should be administered within 1 hour before the next meal. Do not double the dose.
Q6: Can Lixisenatide be used with other diabetes medications?
A: Yes, it can be used with metformin, sulfonylureas, or basal insulin, with dose adjustments for the latter two to mitigate hypoglycemia. The combination of basal insulin and a sulfonylurea with lixisenatide is not recommended.
Q7: Are there any specific monitoring requirements for patients on Lixisenatide?
A: Regular monitoring of blood glucose, HbA1c, and renal function is recommended. Patients should also be monitored for signs and symptoms of pancreatitis and hypersensitivity reactions.
Q8: Is Lixisenatide safe for use during pregnancy or breastfeeding?
A: No, it is contraindicated during pregnancy and should be avoided during breastfeeding.
Q9: How does lixisenatide affect gastric emptying?
A: Lixisenatide slows gastric emptying, which can impact the absorption of other oral medications. It can also contribute to feelings of satiety or fullness.
Q10. What is the mechanism of action of Lixisenatide?
A: Lixisenatide binds to and activates GLP-1 receptors in the pancreas, which stimulates glucose-dependent insulin secretion, suppresses glucagon secretion, and slows gastric emptying.
