Introduction
Soliqua (insulin glargine and lixisenatide) is a fixed-ratio combination product indicated for the treatment of type 2 diabetes mellitus in adults. It combines a long-acting basal insulin analog (insulin glargine) with a glucagon-like peptide-1 (GLP-1) receptor agonist (lixisenatide) to provide dual mechanisms of glucose control in a single daily injection.
Mechanism of Action
Soliqua works through two complementary mechanisms:
- Insulin glargine: Provides basal insulin coverage by facilitating cellular glucose uptake, regulating carbohydrate metabolism, and inhibiting hepatic glucose production
- Lixisenatide: A GLP-1 receptor agonist that enhances glucose-dependent insulin secretion, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying
This combination addresses both fasting and postprandial hyperglycemia through synergistic mechanisms.
Indications
Soliqua is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when both basal insulin and lixisenatide are appropriate treatments.
Dosage and Administration
- Initial dosing: Start with 15 units (15 units insulin glargine/5 mcg lixisenatide) once daily
- Titration: Increase by 2-4 units every week based on fasting glucose measurements
- Maximum dose: 60 units (60 units insulin glargine/20 mcg lixisenatide) once daily
- Administration: Subcutaneous injection in the abdomen, thigh, or upper arm, once daily within 1 hour before the first meal of the day
- Special populations:
- Renal impairment: Use caution in moderate to severe impairment (CrCl <60 mL/min) - Hepatic impairment: Use with caution - Geriatric: Consider lower starting doses
Pharmacokinetics
- Absorption:
- Insulin glargine: Slow, prolonged absorption with no pronounced peak - Lixisenatide: Rapid absorption with Tmax of 1-3 hours
- Distribution:
- Insulin glargine: Extensive protein binding - Lixisenatide: Volume of distribution ~100 L
- Metabolism:
- Insulin glargine: Metabolized to active metabolites M1 and M2 - Lixisenatide: Proteolytic degradation with minimal hepatic metabolism
- Elimination:
- Insulin glargine: Terminal half-life ~12 hours - Lixisenatide: Terminal half-life ~3 hours, primarily renal elimination
Contraindications
- Hypersensitivity to insulin glargine, lixisenatide, or any product components
- History of serious hypersensitivity reactions
- During episodes of hypoglycemia
- Patients with type 1 diabetes mellitus
- Patients with diabetic ketoacidosis
- Personal or family history of medullary thyroid carcinoma
- Patients with Multiple Endocrine Neoplasia syndrome type 2
Warnings and Precautions
- Risk of hypoglycemia: Increased risk when combined with other glucose-lowering agents
- Pancreatitis: Discontinue immediately if pancreatitis is suspected
- Thyroid C-cell tumors: Lixisenatide component carries boxed warning for thyroid C-cell tumors in rodents
- Renal impairment: Use with caution; may experience worsened renal function
- Hypersensitivity reactions: Serious reactions including anaphylaxis reported
- Never share Soliqua pens between patients
- Cardiovascular effects: Monitor in patients with history of cardiovascular disease
Drug Interactions
- Other antidiabetic agents: Increased risk of hypoglycemia when combined with insulin secretagogues or insulin
- Drugs that affect gastric emptying: May alter lixisenatide absorption (e.g., anticholinergics, opioids)
- Warfarin: Monitor INR more frequently when initiating or changing Soliqua dose
- Oral medications: Administer oral medications 1 hour before Soliqua injection
- Beta-blockers, clonidine, lithium salts, alcohol: May potentiate or weaken glucose-lowering effect
Adverse Effects
Common (≥5%):- Hypoglycemia (30%)
- Nausea (20%)
- Diarrhea (10%)
- Headache (10%)
- Upper respiratory tract infection (7%)
- Nasopharyngitis (6%)
- Severe hypoglycemia
- Pancreatitis
- Hypersensitivity reactions
- Renal impairment
- Severe gastrointestinal adverse reactions
Monitoring Parameters
- Glycemic control: Fasting glucose, HbA1c every 3 months
- Hypoglycemia: Regular assessment of signs and symptoms
- Renal function: Serum creatinine at baseline and periodically
- Pancreatitis: Monitor for abdominal pain with or without vomiting
- Thyroid nodules: Baseline and periodic neck examination
- Weight: Regular monitoring
- Injection sites: For lipodystrophy, redness, swelling, or itching
Patient Education
- Administration: Proper injection technique and rotation of injection sites
- Hypoglycemia: Recognition and treatment of low blood sugar
- Timing: Inject within 1 hour before the first meal of the day
- Storage: Refrigerate unused pens; in-use pen may be kept at room temperature for up to 28 days
- Missed dose: If missed, inject within 1 hour before next meal; do not double dose
- Concomitant medications: Inform healthcare provider of all medications being taken
- Sick days: Guidance on management during illness
- Pregnancy planning: Discuss with healthcare provider before conception
- Never share pens: Risk of blood-borne pathogen transmission
References
1. FDA Prescribing Information: Soliqua (insulin glargine and lixisenatide) injection. 2022 2. Rosenstock J, et al. Benefits of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide, Versus Insulin Glargine and Lixisenatide Monocomponents in Type 2 Diabetes Inadequately Controlled on Oral Agents: The LixiLan-O Randomized Trial. Diabetes Care. 2016;39(11):2026-2035 3. Aroda VR, et al. Efficacy and safety of LixiLan, a titratable fixed-ratio combination of insulin glargine plus lixisenatide in type 2 diabetes inadequately controlled on basal insulin and metformin: The LixiLan-L randomized trial. Diabetes Care. 2016;39(11):1972-1980 4. American Diabetes Association. Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1) 5. Davies MJ, et al. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2022;45(11):2753-2786 6. Product Monograph: Soliqua. Sanofi-Aventis Canada Inc. 2022