Insulin Glargine and Lixisenatide
Medically reviewed by Drugs.com. Last updated on Aug 9, 2020.
(IN soo lin GLAR jeen & lix i SEN a tide)
- Glargine Insulin and Lixisenatide
- Lixisenatide and Insulin Glargine
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Pen-injector, Subcutaneous:
Soliqua: 100/33: Insulin glargine 100 units and lixisenatide 33 mcg per mL (3 mL) [contains metacresol]
Brand Names: U.S.
- Antidiabetic Agent, Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist
- Insulin, Long-Acting
Refer to individual agents.
Use: Labeled Indications
Diabetes mellitus, type 2, treatment: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Hypersensitivity to insulin glargine, lixisenatide, or any component of the formulation; during episodes of hypoglycemia.
Canadian labeling: Additional contraindications (not in US labeling): Patients with a personal or family history of medullary thyroid carcinoma; patients with multiple endocrine neoplasia syndrome type 2; pregnancy; breastfeeding.
Diabetes mellitus, type 2, treatment:
Note: Due to lack of additive glycemic benefit, avoid concomitant use with a dipeptidyl peptidase-4 inhibitor (ADA/EASD [Davies 2018]). Consider a dose reduction (eg, by 50%) or discontinuation of insulin secretagogues (sulfonylureas, meglitinides) to avoid hypoglycemia (AACE/ACE [Garber 2020]; ADA/EASD [Davies 2018]).
Note: Discontinue therapy with basal insulin or a GLP-1 agonist prior to initiation of the combination product.
Patients naive to basal insulin or a GLP-1 agonist, or currently on a GLP-1 agonist or <30 units of basal insulin/day: 15 units (insulin glargine 15 units/lixisenatide 5 mcg) once daily.
Patients currently on 30 to 60 units of basal insulin/day, with or without a GLP-1 agonist: 30 units (insulin glargine 30 units/lixisenatide 10 mcg) once daily.
Dose titration: Titrate the dosage upwards or downwards by 2 to 4 units (insulin glargine 2 to 4 units/lixisenatide 0.66 to 1.32 mcg) every week until the desired fasting plasma glucose is achieved; usual dosage range: 15 units (insulin glargine 15 units/lixisenatide 5 mcg) to 60 units (insulin glargine 60 units/lixisenatide 20 mcg)/day. Maximum dose: 60 units (insulin glargine 60 units/lixisenatide 20 mcg)/day.
Missed dose: If a dose is missed, resume with the next scheduled dose. Do not double dose or increase the dose to make up for the missed dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Refer to adult dosing; use with caution
SubQ: For SubQ use only. Do not administer IM, IV, or via an insulin pump. Cold injections should be avoided. Inject into the abdomen, thigh, or upper arm. Rotate injection sites for each dose; do not use the same site for each injection to avoid lipodystrophy or localized cutaneous amyloidosis. Rotating from an injection site where lipodystrophy/cutaneous amyloidosis is present to an unaffected site may increase risk of hypoglycemia. Administer within one hour before the first meal of the day, preferably the same meal each day. Solution should appear clear and colorless; do not use if particulate matter or coloration is seen. Do not split the dose. Do not mix or dilute with any other insulin or solution. Prefilled pen dials in 1-unit increments.
Individualized medical nutrition therapy based on American Diabetes Association recommendations is an integral part of therapy.
Prior to initial use, store pens refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze (discard if frozen). Protect from light. After initial use, store at room temperature <25°C (<77°F) and use within 28 days. Replace the pen cap after each use, do not store with needle attached.
Alpha-Glucosidase Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with an alpha-glucosidase inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Beta-Blockers: May enhance the hypoglycemic effect of Insulins. Monitor therapy
Dipeptidyl Peptidase-IV Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Edetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulins. Monitor therapy
Estrogen Derivatives (Contraceptive): Lixisenatide may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Administer oral contraceptives 1 hour before or at least 11 hours after administration of lixisenatide. Consider therapy modification
Glucagon-Like Peptide-1 Agonists: May enhance the hypoglycemic effect of Insulins. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Consider therapy modification
Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy
Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Insulins: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Insulins. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Consider therapy modification
Liraglutide: May enhance the hypoglycemic effect of Insulins. Management: Consider reducing the liraglutide dose if coadministered with insulin. Prescribing information for the Saxenda brand of liraglutide recommends a dose decrease of 50%. Monitor blood glucose for hypoglycemia. Consider therapy modification
Macimorelin: Insulins may diminish the diagnostic effect of Macimorelin. Avoid combination
Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Metreleptin: May enhance the hypoglycemic effect of Insulins. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely for signs and symptoms of hypoglycemia. Consider therapy modification
Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Pioglitazone: May enhance the adverse/toxic effect of Insulins. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination. Management: If insulin is combined with pioglitazone, consider insulin dose reductions to avoid hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure, and consider pioglitazone dose reduction or discontinuation if heart failure occurs Consider therapy modification
Pramlintide: May enhance the hypoglycemic effect of Insulins. Management: Upon initiation of pramlintide, decrease mealtime insulin dose by 50% to reduce the risk of hypoglycemia. Monitor blood glucose frequently and individualize further insulin dose adjustments based on glycemic control. Consider therapy modification
Progestins (Contraceptive): Lixisenatide may decrease the serum concentration of Progestins (Contraceptive). Management: Administer oral contraceptives 1 hour before or at least 11 hours after administration of lixisenatide. Consider therapy modification
Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy
Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Rosiglitazone: Insulins may enhance the adverse/toxic effect of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination. Avoid combination
Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Consider therapy modification
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Sulfonylureas: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Consider therapy modification
Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Also see individual agents.
Endocrine & metabolic: Hypoglycemia (8% to 18%; severe hypoglycemia: ≤1%)
Immunologic: Antibody development (21% to 26%)
1% to 10%:
Gastrointestinal: Diarrhea (7%), nausea (10%), vomiting (3%)
Local: Injection site reaction (2%)
Nervous system: Headache (5%)
Respiratory: Nasopharyngitis (7%), upper respiratory tract infection (6%)
Frequency not defined:
Gastrointestinal: Abdominal distention, abdominal pain, constipation, decreased appetite, dyspepsia, flatulence, gastritis, gastroesophageal reflux disease
Local: Hypertrophy at injection site, lipoatrophy at injection site
Postmarketing: Endocrine & metabolic: Amyloidosis (localized cutaneous at injection site)
Concerns related to adverse effects:
• Antibody formation: Development of antibodies to insulin and lixisenatide may occur; in clinical trials with lixisenatide, high titers were observed in 2.4% of patients and were associated with an attenuated glycemic response. Allergic reactions and injection site reactions were more frequent in antibody positive patients; consider alternative antidiabetic therapy in patients not achieving targeted glycemic control or with worsening glycemic control and/or significant allergic or injection site reactions.
• Hypersensitivity: Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with lixisenatide and with insulin glargine; discontinue use if hypersensitivity reactions occur and treat promptly as indicated. It is not known if patients with a history of hypersensitivity to other GLP-1 agonists are at increased risk for hypersensitivity reactions with lixisenatide; patients with prior serious reactions to similar agents should be monitored closely.
• Hypoglycemia: The most common adverse effect of insulin is hypoglycemia. The timing of hypoglycemia differs among various insulin formulations. Hypoglycemia may result from increased work or exercise without eating; use of long-acting insulin preparations (eg, insulin detemir, insulin glargine, insulin degludec) may delay recovery from hypoglycemia. Profound and prolonged episodes of hypoglycemia may result in convulsions, unconsciousness, temporary or permanent brain damage, or even death. Insulin requirements may be altered during illness, emotional disturbances, or other stressors. Instruct patients to use caution with ethanol; may increase risk of hypoglycemia.
• Hypokalemia: Insulin (especially IV insulin) causes a shift of potassium from the extracellular space to the intracellular space, possibly producing hypokalemia. If left untreated, hypokalemia may result in respiratory paralysis, ventricular arrhythmia and even death. Use with caution in patients at risk for hypokalemia (eg, loop diuretic use). Monitor serum potassium and supplement potassium when necessary.
• Pancreatitis: Cases of acute pancreatitis (including hemorrhagic and necrotizing with some fatalities) have been reported with GLP-1 receptor agonists; monitor for signs and symptoms of pancreatitis (eg, persistent severe abdominal pain which may radiate to the back, and which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue use. Do not resume unless an alternative etiology of pancreatitis is confirmed. Consider alternative antidiabetic therapy in patients with a history of pancreatitis (has not been studied).
• Bariatric surgery:
– Dehydration: Evaluate, correct, and maintain postsurgical fluid requirements and volume status prior to initiating therapy, and closely monitor the patient for the duration of therapy; acute and chronic kidney failure exacerbation may occur. A majority of cases occurred in patients with nausea, vomiting, diarrhea, and/or dehydration. Nausea is common and fluid intake may be more difficult after gastric bypass, sleeve gastrectomy, and gastric band (Mechanick 2013).
– Excessive glucagon-like peptide-1 exposure: Closely monitor for efficacy and assess for signs and symptoms of pancreatitis if therapy is initiated after surgery; gastric bypass and sleeve gastrectomy (but not gastric band) significantly increase endogenous postprandial glucagon-like peptide-1 (GLP-1) concentrations (Korner 2009; Peterli 2012). Administration of exogenous GLP-1 agonists may be redundant to surgery effects.
– Type 2 diabetes, hypoglycemia: Closely monitor insulin dose requirement throughout active weight loss with a goal of eliminating antidiabetic therapy or transitioning to agents without hypoglycemic potential; hypoglycemia after gastric bypass, sleeve gastrectomy, and gastric band may occur (Mechanick 2013). Insulin secretion and sensitivity may be partially or completely restored early after these procedures (gastric bypass is most effective, followed by sleeve and finally band) (Korner 2009; Peterli 2012). Monitoring of hospital insulin requirements is recommended to guide discharge insulin dose. Rates and timing of type 2 diabetes improvement and resolution vary widely by patient; insulin dose reduction of 75% has been suggested after gastric bypass for patients without severe β-cell failure (fasting c-peptide <0.3 nmol/L) (Cruijsen 2014).
– Weight gain: Insulin therapy is preferred if antidiabetic therapy is required during the perioperative period (Mechanick 2019). Evaluate risk versus benefit of long-term postoperative use and consider alternative therapy due to potential for insulin-induced weight gain (Apovian 2015).
• Cardiac disease: Concurrent use with peroxisome proliferator-activated receptor (PPAR)-gamma agonists, including thiazolidinediones (TZDs) may cause dose-related fluid retention and lead to or exacerbate heart failure, particularly when used in combination with insulin. If PPAR-gamma agonists are prescribed, monitor for signs and symptoms of heart failure. If heart failure develops, consider PPAR-gamma agonist dosage reduction or therapy discontinuation.
• Gastroparesis: Lixisenatide slows gastric emptying and is not recommended for use in patients with gastroparesis (has not been studied); do not initiate therapy in patients with severe gastroparesis.
• Renal impairment: Use with caution in patients with renal impairment. Dosage adjustments may be necessary. Patients with mild to moderate renal impairment (eGFR ≥30 to 89 mL/minute/1.73 m2) may be at increased risk of adverse effects (eg, diarrhea, nausea, vomiting) which may lead to dehydration, acute kidney injury, and worsening of chronic renal failure. There is limited experience with severe impairment (eGFR 15 to <30 mL/minute/1.73 m2); lixisenatide exposure may be increased in these patients. Monitor all patients with renal impairment closely for decreasing renal function. Use is not recommended in patients with end-stage renal disease (eGFR <15 mL/minute/1.73 m2) (has not been studied).
• Hepatic impairment: Use with caution in patients with hepatic impairment. Dosage adjustments may be necessary.
Dosage form specific issues:
• Multiple dose injection pens: According to the Centers for Disease Control and Prevention (CDC), pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).
• Appropriate use: Not approved for use in patients with diabetic ketoacidosis or patients with type 1 diabetes mellitus.
• Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.
Diabetes mellitus: Plasma glucose (typically before meals and snacks and at bedtime; occasionally additional monitoring may be required), electrolytes, HbA1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2020]), hepatic function, weight; potassium (in patients at risk for hypokalemia); renal function, signs/symptoms of pancreatitis.
Gestational diabetes mellitus: Blood glucose 4 times daily (1 fasting and 3 postprandial) until well controlled, then as appropriate (ACOG 2018).
Adverse events were observed in some animal reproduction studies. Refer to individual monographs.
What is this drug used for?
• It is used to lower blood sugar in patients with high blood sugar (diabetes).
All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
• Upset stomach
• Throwing up
• Stomach pain
• Passing gas
• Not hungry
• Nose or throat irritation
• Common cold symptoms
• Injection site irritation
WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
• Pancreatitis like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up
• Kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain
• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat
• Change in eyesight
• Dizziness or passing out
• Injection site thick skin, pits, or lumps
• Shortness of breath, a big weight gain, or swelling in the arms or legs
• Low blood sugar like dizziness, headache, feeling sleepy, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating
• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.
Frequently asked questions
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