Note: Due to lack of additive glycemic benefit, avoid concomitant use with a dipeptidyl peptidase-4 inhibitor (ADA/EASD [Davies 2018]). May require a dose reduction of insulin and/or insulin secretagogues (sulfonylureas, meglitinides) to avoid hypoglycemia (AACE/ACE [Garber 2020]).
Diabetes mellitus, type 2, treatment:
Note: May be used as an adjunctive agent or alternative monotherapy for select patients, including those in whom initial therapy with lifestyle intervention and metformin failed, or those who cannot take metformin; use is not associated with improvements in cardiovascular outcomes (ADA 2020; Pfeffer 2015).
SUBQ: Initial: 10 mcg once daily for 14 days; on day 15 increase to 20 mcg once daily. Maintenance dose: 20 mcg once daily.
Missed dose: If dose is missed, administer within one hour of next meal.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
eGFR ≥30 to 89 mL/minute/1.73 m2: No dosage adjustment necessary; monitor closely for increased adverse GI effects (eg, diarrhea, nausea, vomiting) which may lead to dehydration and worsening of renal function.
eGFR 15 to 29 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling (limited data); exposure is increased in these patients. Monitor closely for increased adverse GI effects (eg, diarrhea, nausea, vomiting) which may lead to dehydration and worsening of renal function.
eGFR <15 mL/minute/1.73 m2: Use is not recommended (has not been studied).
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); however, dosage adjustment not likely as hepatic impairment is not expected to affect lixisenatide pharmacokinetics.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Pen-injector Kit, Subcutaneous:
Adlyxin Starter Pack: 10 mcg/0.2 mL & 20 mcg/0.2 mL (6 mL) [contains metacresol]
Solution Pen-injector, Subcutaneous:
Adlyxin: 20 mcg/0.2 mL (3 mL) [contains metacresol]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Pen-injector, Subcutaneous:
Adlyxine: 10 mcg/0.2 mL (3 mL); 20 mcg/0.2 mL (3 mL) [contains metacresol]
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/208471s005lbl.pdf#page=24, must be dispensed with this medication.
Subcutaneous: Administer subcutaneously in the abdomen, thigh, or upper arm. Rotate injection sites for each dose; do not use the same site for each injection. 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. For each new prefilled pen, activate the device before the first injection by attaching a pen needle, pulling the injection button out, and then injecting into the air or a container (continue to depress the button until it stops and for an additional 2 seconds); these activation steps should not be performed for subsequent injections. Use a new needle for each injection. Once injected, continue to depress the button until it stops and for an additional 2 seconds. Then, remove the needle. Refer to manufacturer’s instructions for further details.
Diabetes mellitus, type 2, treatment: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Gastrointestinal: Gastrointestinal signs and symptoms (40%; abdominal distension [2%], constipation [3%], diarrhea [8%], dyspepsia [3%], nausea [25%], upper abdominal pain [2%], vomiting [10%])
Immunologic: Antibody development (70%; attenuated glycemic response: 2%)
1% to 10%:
Local: Injection-site reaction (4%; including erythema at injection site, injection-site pruritus, pain at injection site)
Nervous system: Dizziness (7%), headache (9%)
<1%: Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction
Postmarketing:
Gastrointestinal: Cholecystitis, cholelithiasis (requiring cholecystectomy), pancreatitis (acute, chronic, and edematous) (Chis 2018)
Renal: Acute kidney injury, exacerbation of renal failure
History of severe hypersensitivity to lixisenatide or any component of the formulation.
Concerns related to adverse effects:
• Anti-lixisenatide antibodies: Use may be associated with the development of anti-lixisenatide antibodies. In clinical trials, 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.
• Gallbladder disease: Use of glucagon-like peptide-1 (GLP-1) agonists may increase risk of gallbladder and bile duct disease, including cholelithiasis and cholecystitis (Faillie 2016; Monami 2017; Pfeffer 2015). Cholelithiasis and cholecystitis have been reported with lixisenatide use.
• Hypersensitivity: Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported; 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.
• Pancreatitis: Cases of acute pancreatitis (including hemorrhagic and necrotizing with some fatalities) have been reported; 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.
Disease-related concerns:
• 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 GLP-1 concentrations (Korner 2009; Peterli 2012). Administration of exogenous GLP-1 agonists may be redundant to surgery effects.
• 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 mild renal impairment (eGFR ≥60 to 89 mL/minute/1.73 m2) or moderate renal impairment (≥30 to <60 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).
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).
Other warnings/precautions:
• Appropriate use: Not for use in patients with diabetic ketoacidosis or patients with type 1 diabetes mellitus.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Beta-Blockers (Beta1 Selective): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Beta-Blockers (Nonselective): May enhance the hypoglycemic effect of Antidiabetic Agents. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Bortezomib: May enhance the therapeutic effect of Antidiabetic Agents. Bortezomib may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Etilefrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Hormonal Contraceptives: May diminish the therapeutic effect of Lixisenatide. Lixisenatide may decrease the serum concentration of Hormonal Contraceptives. Management: Administer oral hormonal contraceptives 1 hour before or at least 11 hours after administration of lixisenatide. Additionally, monitor blood glucose more frequently when patients treated with lixisenatide initiate therapy with a hormonal contraceptive. Risk D: Consider therapy modification
Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: 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. Risk D: Consider therapy modification
Liraglutide: May enhance the adverse/toxic effect of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid combination
Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Meglitinides: Glucagon-Like Peptide-1 Agonists may enhance the hypoglycemic effect of Meglitinides. Management: Consider meglitinide dose reductions when used in combination with glucagon-like peptide-1 agonists, particularly when also used with basal insulin. Risk D: Consider therapy modification
Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: 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. Risk C: Monitor therapy
Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Semaglutide: May enhance the adverse/toxic effect of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid combination
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. Risk D: 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. Risk D: Consider therapy modification
Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Glucagon-like peptide-1 (GLP-1) receptor agonists are not recommended for patients with type 2 diabetes mellitus planning to become pregnant. Patients who could become pregnant should use effective contraception during therapy. Transition to a preferred therapy should be initiated prior to conception and contraception should be continued until glycemic control is achieved (ADA 2021; Alexopoulos 2019; Egan 2020)
Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major malformations, stillbirth, and macrosomia (ACOG 201 2018). To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2021; Blumer 2013).
Agents other than lixisenatide are currently recommended to treat diabetes mellitus in pregnancy (ADA 2021).
It is not known if lixisenatide is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy
Plasma glucose; renal function; signs/symptoms of pancreatitis (eg, persistent severe abdominal pain that may radiate to the back and that may or may not be accompanied by vomiting); signs/symptoms of gallbladder disease; gallbladder studies and further clinical assessment are indicated if cholelithiasis is suspected.
HbA1c: Monitor at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; monitor quarterly in patients in whom treatment goals have not been met, or with therapy change. Note: In patients prone to glycemic variability (eg, patients with insulin deficiency), or in patients whose HbA1c is discordant with serum glucose levels or symptoms, consider evaluating HbA1c in combination with blood glucose levels and/or a glucose management indicator (ADA 2021; KDIGO 2020).
Recommendations for glycemic control in patients with diabetes:
Nonpregnant adults (ADA 2021):
HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics). Note: In patients using a continuous glucose monitoring system, a goal of time in range >70% with time below range <4% is recommended and is similar to a goal HbA1c <7%.
Preprandial capillary blood glucose: 80 to 130 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).
Peak postprandial capillary blood glucose (~1 to 2 hours after a meal): <180 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).
Older adults (≥65 years of age) (ADA 2021):
Note: Consider less strict targets in patients who are using insulin and/or insulin secretagogues (sulfonylureas, meglitinides) (ES [LeRoith 2019]).
HbA1c: <7% to 7.5% (healthy); <8% to 8.5% (complex/intermediate health). Note: Individualization may be appropriate based on patient and caregiver preferences and/or presence of cognitive impairment. In patients with very complex or poor health (ie, limited remaining life expectancy), consider making therapy decisions based on avoidance of hypoglycemia and symptomatic hyperglycemia rather than HbA1c level.
Preprandial capillary blood glucose: 80 to 130 mg/dL (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health).
Bedtime capillary blood glucose: 80 to 180 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health).
Classification of hypoglycemia (ADA 2021):
Level 1: 54 to 70 mg/dL; hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.
Level 2: <54 mg/dL; threshold for neuroglycopenic symptoms; requires immediate action.
Level 3: Hypoglycemia associated with a severe event characterized by altered mental and/or physical status requiring assistance.
Lixisenatide is a selective glucagon-like peptide-1 (GLP-1) receptor agonist. Acting on the same receptor as the endogenous hormone incretin, lixisenatide increases glucose-dependent insulin secretion, decreases inappropriate glucagon secretion, and slows gastric emptying.
Distribution: Vz/F: ~100 L
Metabolism: Presumed to undergo proteolytic degradation
Half-life elimination: ~3 hours
Time to peak: 1 to 3.5 hours
Excretion: Urine
Altered kidney function: Compared to healthy subjects (CrCl ≥90 mL/minute), lixisenatide Cmax and AUC were increased by 60% and 34% in mild renal impairment (CrCl 60 to 89 mL/minute), by 42% and 69% in moderate renal impairment (CrCl 30 to 59 mL/minute), and by 83% and 124% in severe renal impairment (CrCl 15 to 29 mL/minute) respectively.
Pen-injector Kit (Adlyxin Starter Pack Subcutaneous)
10 & 20MCG/0.2ML (per mL): $135.71
Solution Pen-injector (Adlyxin Subcutaneous)
20MCG/0.2ML (per mL): $135.70
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
