Usage
Insulin glargine + lixisenatide is prescribed as an adjunct to diet and exercise for improving glycemic control in adults with type 2 diabetes mellitus. It is a combination medication consisting of a long-acting insulin analog (insulin glargine) and a glucagon-like peptide-1 (GLP-1) receptor agonist (lixisenatide). Its pharmacological classifications are antidiabetic combination, long-acting insulin, and GLP-1 receptor agonist.
The mechanism of action involves two components: insulin glargine, which lowers blood glucose by facilitating glucose uptake into cells and inhibiting hepatic glucose production, and lixisenatide, which increases glucose-dependent insulin secretion, decreases glucagon secretion, and slows gastric emptying.
Alternate Names
This fixed-dose combination medication is most commonly known as Soliqua 100/33 in the United States and Suliqua in Europe and other regions. There are two available pre-filled pen options: Suliqua (10-40) and Suliqua (30-60).
How It Works
Pharmacodynamics: Insulin glargine provides a basal level of insulin, mimicking the body’s natural insulin production. Lixisenatide complements this by increasing insulin release after meals and suppressing glucagon secretion, further aiding glucose control. It also slows gastric emptying.
Pharmacokinetics: Insulin glargine is slowly absorbed from the subcutaneous injection site, providing a relatively constant concentration over 24 hours. Lixisenatide is also absorbed subcutaneously and reaches peak concentration within 1 to 2 hours. Insulin glargine is metabolized to active metabolites M1 and M2, and lixisenatide is primarily eliminated through the kidneys.
Mode of Action: Insulin glargine binds to insulin receptors, activating downstream pathways that promote glucose uptake and glycogen synthesis. Lixisenatide binds to GLP-1 receptors on pancreatic beta cells, enhancing glucose-dependent insulin release.
Receptor Binding: Insulin glargine binds to insulin receptors. Lixisenatide binds to and activates GLP-1 receptors.
Elimination Pathways: Insulin glargine undergoes enzymatic degradation, and its metabolites are primarily excreted through the kidneys. Lixisenatide is predominantly excreted unchanged via the kidneys.
Dosage
Standard Dosage
Adults:
The starting dose depends on previous antidiabetic treatment. For insulin-naive patients or those on less than 30 units of basal insulin daily, a starting dose of 15 units insulin glargine and 5 mcg lixisenatide (15 dose steps of Soliqua 100/33) subcutaneously once daily is recommended. Patients using 30 to 60 units of basal insulin daily may start with 30 dose steps (30 units/10 mcg) once daily. Titration is based on individual patient needs, adjusted by 2-4 dose steps weekly based on fasting plasma glucose and glycemic control goals. The maximum daily dose is 60 units/20 mcg (60 dose steps).
Children:
Use in pediatric patients is not recommended as safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Dose adjustments may be needed based on individual glucose monitoring due to age-related changes in renal function and insulin sensitivity.
- Patients with Renal Impairment: Mild to moderate impairment requires careful monitoring. Severe renal impairment or end-stage renal disease: Use is not recommended due to the potential accumulation of lixisenatide.
- Patients with Hepatic Dysfunction: No dose adjustment is needed for lixisenatide. Frequent glucose monitoring and dose adjustment of insulin glargine may be required.
- Patients with Comorbid Conditions: Consider individual patient needs and adjust the dose accordingly.
Clinical Use Cases
Insulin glargine + lixisenatide is intended for chronic management of type 2 diabetes. Its use in acute settings like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations is not indicated. In such situations, other insulin formulations are preferred due to their faster onset and shorter duration of action.
Dosage Adjustments
Dosage should be individualized and titrated based on fasting plasma glucose, glycemic control goals, and patient response. Close glucose monitoring is recommended during dose adjustments and when other factors are present, such as changes in physical activity, meal patterns, or renal/hepatic function, or when initiating or discontinuing other medications.
Side Effects
Common Side Effects
Nausea, nasopharyngitis, diarrhea, upper respiratory tract infection, hypoglycemia, and injection site reactions.
Rare but Serious Side Effects
Pancreatitis (acute or hemorrhagic), severe hypoglycemia, anaphylaxis, angioedema, and severe hypersensitivity reactions.
Long-Term Effects
Potential long-term effects might include weight changes, hypokalemia, and altered lipid profiles. Regular monitoring for these is important.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include anaphylaxis, angioedema, pancreatitis, and severe hypoglycemia. These require prompt discontinuation of the drug and immediate medical attention.
Contraindications
Absolute contraindications include hypersensitivity to the active substances or any of the excipients, and during episodes of hypoglycemia. It should not be used in patients with type 1 diabetes, diabetic ketoacidosis, or a history of pancreatitis. Relative contraindications include severe renal impairment and end-stage renal disease.
Drug Interactions
Clinically significant interactions can occur with drugs that affect glucose metabolism or gastric emptying. Examples include sulfonylureas, thiazolidinediones, other GLP-1 receptor agonists, and certain oral contraceptives. Close monitoring is recommended when initiating or discontinuing these medications. Alcohol can also potentiate the hypoglycemic effects.
Pregnancy and Breastfeeding
Pregnancy: Not recommended for women of childbearing potential not using contraception. There are limited data in pregnant women. Animal studies with lixisenatide have shown reproductive toxicity.
Breastfeeding: It is unknown whether the components are excreted in human milk. A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment.
Drug Profile Summary
- Mechanism of Action: Dual action: long-acting insulin and GLP-1 receptor agonist to lower blood glucose.
- Side Effects: Nausea, hypoglycemia, diarrhea, nasopharyngitis, injection site reactions, pancreatitis (rare), hypersensitivity reactions (rare).
- Contraindications: Hypersensitivity, type 1 diabetes, diabetic ketoacidosis, history of pancreatitis, severe renal impairment.
- Drug Interactions: Other antidiabetic agents, alcohol.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: individualized starting dose, titrated based on fasting plasma glucose. Maximum: 60 units/20 mcg once daily. Not for pediatric use.
- Monitoring Parameters: Fasting plasma glucose, HbA1c, weight, renal function, and signs of pancreatitis or hypersensitivity reactions.
Popular Combinations
Insulin glargine + lixisenatide is often combined with metformin.
Precautions
- General Precautions: Monitor blood glucose and adjust dose as needed. Watch for signs of pancreatitis and hypersensitivity. Educate patients about hypoglycemia management.
- Specific Populations: Avoid use during pregnancy and breastfeeding. Use with caution in elderly patients and those with renal or hepatic impairment. Not for pediatric use.
- Lifestyle Considerations: Advise patients on diet, exercise, and alcohol consumption.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Insulin Glargine + Lixisenatide?
A: The starting dose depends on previous insulin use. For insulin-naive patients or those on less than 30 units/day, it’s 15 units/5 mcg. For patients on 30-60 units/day, it’s 30 units/10 mcg. The maximum dose is 60 units/20 mcg per day.
Q2: Can it be used in Type 1 Diabetes?
A: No, it’s contraindicated in type 1 diabetes and diabetic ketoacidosis.
Q3: How is it administered?
A: It’s administered subcutaneously once daily, within one hour before the first meal of the day.
Q4: What are the most common side effects?
A: Nausea, hypoglycemia, diarrhea, and nasopharyngitis.
Q5: Are there any serious side effects I should be aware of?
A: Yes, though rare, serious side effects include pancreatitis, anaphylaxis, and angioedema.
Q6: What if a dose is missed?
A: Inject the missed dose within the hour prior to the next meal. If it is close to the time for the next dose, skip the missed dose and continue with the regular schedule. Do not double the dose.
Q7: Can this medication be used during pregnancy?
A: No, it’s not recommended during pregnancy or for women of childbearing potential not using contraception.
Q8: Can this medication be combined with other diabetes medications?
A: Yes, most frequently with metformin. However, do not combine with other GLP-1 receptor agonists.
Q9: What monitoring is needed when a patient starts this medicine?
A: Close blood glucose monitoring, especially during dose titration. Monitor for signs and symptoms of pancreatitis, hypersensitivity, and hypokalemia. Renal and hepatic function should also be checked periodically.
Q10: What patient education is essential when prescribing this medication?
A: Educate patients about proper injection technique, signs and symptoms of hypoglycemia and hyperglycemia, potential side effects, and drug interactions. Advise patients to consult their physician before taking any new medications, including over-the-counter drugs and supplements. Reinforce the importance of adherence to diet and exercise recommendations.
