Liraglutide

Pharmacologic Category

Antidiabetic Agent, Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist

Dosing: Adult

Note: Due to lack of additive glycemic benefit, use in combination with a dipeptidyl peptidase-4 (DPP-4) inhibitor (eg, sitagliptin) should be avoided (Dungan 2019; Nauck 2017).

Diabetes mellitus, type 2, treatment:

Note: May be used as an adjunctive agent or alternative monotherapy for select patients, including those who fail initial therapy with lifestyle intervention and metformin or who cannot take metformin. Liraglutide may be preferred as an additional antidiabetic agent or alternative first-line agent in patients with atherosclerotic cardiovascular disease (given liraglutide's demonstrated cardiovascular benefit) and/or in patients with an HbA_1c relatively far from goal (HbA_1c >9% and type 1 diabetes is not likely) (ACC [Das 2018]; ADA 2019; Dungan 2019; Marso 2016; Wexler 2019).

SubQ: Initial: 0.6 mg once daily for 1 week, then increase to 1.2 mg once daily; if optimal glycemic response is not achieved after an additional week of treatment, may increase further to 1.8 mg once daily. Note: The lower initial dose (0.6 mg daily) is intended to reduce GI symptoms; it does not provide effective glycemic control.

Concomitant use with insulin and/or insulin secretagogues (eg, sulfonylurea): Reduced dose of insulin and/or insulin secretagogues may be needed.

Obesity and select overweight patients:

Note: For use as an adjunct to diet and exercise in obese patients or overweight patients with ≥1 weight-associated comorbidity (eg, hypertension, dyslipidemia). Considered a preferred pharmacologic weight-loss option in obese and overweight patients with type 2 diabetes mellitus, particularly in patients with atherosclerotic cardiovascular disease (AACE/ACE [Garvey 2016]; Endocrine Society [Apovian 2015]; Endocrine Society [Bray 2018]; Marso 2016; Perreault 2019).

SubQ: Initial: 0.6 mg once daily for 1 week; increase by 0.6 mg daily at weekly intervals to a target dose of 3 mg once daily. If the patient cannot tolerate an increased dose during dose escalation, consider delaying dose escalation for 1 additional week. According to the manufacturer, efficacy has not been established at doses <3 mg/day; however, some experts will continue a patient on the maximum tolerated dose (even if <3 mg/day) if goal weight loss is achieved on that dose (Perreault 2019).

Note: Evaluate change in body weight after 12 weeks at maximum tolerated dose or 16 weeks after initiation of therapy; discontinue if at least 4% to 5% of baseline body weight loss has not been achieved (ADA 2019; manufacturer's labeling).

Missed doses: In the event of a missed dose, the once-daily regimen can be resumed with the next scheduled dose (an extra dose or an increase in the next dose should not be attempted); if >3 days have passed since the last liraglutide dose, reinitiate therapy at 0.6 mg/day to avoid GI symptoms and titrate according to clinical judgment considering previous GI tolerability.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

No dosage adjustment necessary; use with caution when initiating therapy and with dose escalation. There is limited data in patients with ESRD.

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary; use with caution due to limited experience.

Dosing: Pediatric

Diabetes mellitus, type 2; adjunct to diet and exercise: Children ≥10 years and Adolescents: Victoza: SubQ: Initial: 0.6 mg once daily for at least 1 week; may increase by 0.6 mg/day increments at weekly intervals to achieve glycemic control (week 2: increase to 1.2 mg once daily; week 3: increase to 1.8 mg once daily); maximum daily dose: 1.8 mg/day. In clinical trials, all patients were on concomitant stable doses of metformin (1,000 to 2,000 mg/day) with or without basal insulin; patients on basal insulin had insulin dose reductions (by 20%) during liraglutide therapy titration (Tamborlane 2019).

Missed doses: If more than 3 days of therapy are missed, therapy should be restarted at the initial dose (0.6 mg/day) and retitrated to avoid GI symptoms.

Obesity; adjunct to strict lifestyle interventions:

Children ≥12 years and Adolescents ≤17 years: Limited data available (Fox 2019; Srivastava 2019): SubQ: Initial: 0.6 mg once daily; increase by 0.6 mg/day increments at weekly intervals up to target dose of 3 mg once daily. Dosing based on a double-blind, parallel-group, placebo-controlled trial including 14 subjects in liraglutide treatment group (age range: 12 to 17 years; Tanner stage: 2 to 5) with a BMI corresponding to both a 95th percentile for age and sex and an adult BMI of 30 to 45 kg/m². After 6 weeks of therapy, results showed a decrease in mean BMI z-score and body weight with treatment and placebo; however, the difference between treatment and placebo did not reach statistical significance; safety analysis reported similar safety and tolerability profile as adults treated for obesity (Danne 2017)

Adolescents ≥18 years: Saxenda: SubQ: Initial: 0.6 mg once daily for 1 week; increase by 0.6 mg/day increments at weekly intervals to a target dose of 3 mg once daily. If the patient cannot tolerate an increased dose during dose escalation, consider delaying dose escalation for one additional week. If the 3 mg daily dose is not tolerated, discontinue use as efficacy has not been established at lower doses. After 16 weeks of therapy, assess body weight; if patient has not lost ≥4% of baseline bodyweight, discontinue therapy since patient is unlikely to achieve meaningful and sustainable results with liraglutide.

Missed doses: If more than 3 days of therapy are missed, therapy should be restarted at the initial dose (0.6 mg/day) and retitrated to avoid GI symptoms.

Dosing: Renal Impairment: Pediatric

Diabetes mellitus, type 2: Children ≥10 years and Adolescents: Victoza: SubQ:

Baseline: No dosage adjustment necessary; use with caution when initiating therapy and with dose escalation. There is limited data in patients with end-stage kidney disease (ESKD); use with caution.

During therapy; with or without preexisting kidney disease: Acute renal failure has been reported or worsening of chronic kidney disease (may require hemodialysis); provide supportive care; consider discontinuation of liraglutide or other causative agents as necessary.

Obesity, adjunct therapy:

Children ≥12 years and Adolescents ≤17 years: Limited data available: Saxenda: SubQ: Severe renal impairment or ESKD: Use not recommended (Srivastava 2019).

Adolescents ≥18 years: Saxenda: SubQ: Data in patients with any degree of kidney impairment is limited (including ESKD); acute renal failure has been reported or worsening of chronic kidney disease (may require hemodialysis); use with caution in this patient population.

Dosing: Hepatic Impairment: Pediatric

Children ≥10 years and Adolescents: SubQ: No dosage adjustment necessary; use with caution due to limited experience.

Use: Labeled Indications

Chronic weight management (Saxenda): As an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index of ≥30 kg/m² (obese) or ≥27 kg/m² (overweight) in the presence of at least one weight-related comorbid condition (eg, hypertension, type 2 diabetes mellitus, dyslipidemia).

Diabetes mellitus, type 2 (Victoza): As an adjunct to diet and exercise to improve glycemic control in children ≥10 years of age, adolescents, and adults with type 2 diabetes mellitus; risk reduction of major cardiovascular events (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease.

* See Uses in AHFS Essentials for additional information.

Class and Related Monographs

Glucagonlike Peptide 1 Receptor Agonists

Clinical Practice Guidelines

Diabetes Mellitus:

American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE), “Consensus Statement on the Comprehensive Type 2 Diabetes Management Algorithm - 2019 Executive Summary,” January 2019

American Diabetes Association, “Standards of Medical Care in Diabetes - 2019,” January 2019

American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD), “Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the ADA and the EASD,” December 2018

Diabetes Canada, “Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada,” 2018

Obesity:

AACE/ACE, “Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity,” July 2016

The Endocrine Society, “Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline,” 2015

Administration: Subcutaneous

Inject subcutaneously in the upper arm, thigh, or abdomen. Do not inject intravenously or intramuscularly. Administer without regard to meals or time of day. Change needle with each administration. Use only if clear, colorless, and free of particulate matter. Do not share pens between patients even if needle is changed. If using concomitantly with insulin, administer as separate injections (do not mix); may inject in the same body region as insulin, but not adjacent to one another.

Administration: Pediatric

SubQ: Inject subcutaneously in the upper arm, thigh, or abdomen. Do not inject intravenously or intramuscularly. Administer any time of day without regard to meals. If using concomitantly with insulin, administer as separate injections (do not mix in same syringe); may inject in the same body region, but not adjacent to one another. Change needle with each administration; do not share pens between patients even if needle is changed. In pediatric obesity trials, doses were administered at 8 AM (± 2 hours) (Danne 2017).

Missed doses: If a dose is missed, the once-daily regimen can be resumed with the next scheduled dose (an extra dose or an increase in the next dose should not be attempted); if >3 days have passed since the last liraglutide dose, reinitiate therapy at initial doses to avoid GI symptoms and titrate according to prescriber discretion (see Dosing: Pediatric).

Dietary Considerations

Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 2]).

Note: Prepared/prefilled syringes may be excluded from some hazardous drug handling requirements; assess risk to determine appropriate containment strategy (USP-NF 2018). Refer to institution-specific handling policies and procedures.

Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. The National Institute for Occupational Safety and Health recommends double gloving and a protective gown during subcutaneous administration from a prepared/prefilled syringe (NIOSH 2016).

Storage/Stability

Prior to initial use, store at 2°C to 8°C (36°F to 46°F); after initial use, may be stored at 2°C to 8°C (36°F to 46°F) or at 15°C to 30°C (59°F to 86°F). Do not freeze (discard if freezing occurs) or store directly adjacent to the refrigerator cooling element. Protect from heat and light. Pen should be discarded 30 days after initial use.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to lower blood sugar in patients with high blood sugar (diabetes).

• It is used to lower the chance of heart attack, stroke, and death in some people.

• It is used to help you lose weight.

Frequently reported side effects of this drug

• Headache

• Diarrhea

• Constipation

• Nausea

• Vomiting

• Lack of appetite

• Stuffy nose

• Sore throat

• Back pain

• Abdominal pain

• Loss of strength and energy

• Injection site irritation

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Thyroid cancer like new lump or swelling in the neck, pain in the front of the neck, persistent cough, persistent change in voice like hoarseness, or difficulty swallowing or breathing.

• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting.

• Gallstones like pain in the upper right abdominal area, right shoulder area, or between the shoulder blades; yellow skin; or fever with chills.

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.

• Dizziness

• Passing out

• Fast heartbeat

• Abnormal heartbeat

• Mood changes

• Behavioral changes

• Depression

• Thoughts of suicide

• Slurred speech

• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of 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 brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Other safety concerns:

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information, and as follows, must be dispensed with this medication:

Saxenda: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/206321s004s006lbl.pdf#page=26

Victoza: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022341s031lbl.pdf#page=34

Contraindications

Prior serious hypersensitivity to liraglutide or any component of the formulation; history of or family history of MTC; patients with multiple endocrine neoplasia syndrome type 2 (MEN2); pregnancy (Saxenda).

Canadian labeling: Additional contraindications (not in US labeling): Pregnancy (Saxenda, Victoza); breastfeeding

Warnings/Precautions

Concerns related to adverse effects:

• Antibody formation: Use may be associated with the development of anti-liraglutide antibodies. Antibody formation was not associated with a loss of efficacy; however, patients with the highest titers of anti-liraglutide antibodies had no reduction in HbA_1C.

• Cardiovascular effects: Increased resting heart rate has been observed in placebo-controlled trials; monitoring is recommended. Discontinue use in patients who experience a sustained increase in resting heart rates.

• Gallbladder disease: Use of GLP-1 agonists may increase risk of gallbladder and bile duct disease (Faillie 2016). Cholelithiasis and cholecystitis have been reported in patients treated with liraglutide with the majority of patients requiring hospitalization or cholecystectomy; gallbladder studies and further clinical assessment are indicated if cholelithiasis is suspected.

• GI symptoms: Most common reactions are GI related; these symptoms may be dose related and may decrease in frequency/severity with gradual titration and continued use. Discontinue use if volume depletion develops (eg, due to nausea, vomiting, diarrhea) (AACE [Garvey 2016]).

• Hypersensitivity reactions: Serious hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported with use; permanently discontinue therapy in the event of a hypersensitivity reaction. Use with caution in patients with a history of anaphylaxis or angioedema to other GLP-1 receptor agonists; potential for cross-sensitivity is unknown.

• Pancreatitis: Cases of acute and chronic pancreatitis (including fatal and nonfatal, hemorrhagic or necrotizing pancreatitis) 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. It is not known if liraglutide increases risk for development of pancreatitis in patients with a history of pancreatitis.

• Psychiatric effects: Suicidal behavior, with one case of attempted suicide, has been reported in patients treated for obesity; monitor for new or worsening depression, suicidal thoughts or behavior, or unusual changes in mood or behavior. Discontinue use if suicidal thoughts or behaviors occur. Avoid use in patients with history of suicidal attempts or active suicidal ideation.

• Renal effects: Acute renal failure and chronic renal failure exacerbation (including severe cases requiring hemodialysis) have been reported; some cases have been reported in patients with no known preexisting renal disease. Reports primarily occurred in patients with nausea, vomiting, diarrhea, or dehydration. Renal dysfunction was usually reversible with appropriate corrective measures, including discontinuation of liraglutide. Risk may be increased in patients receiving concomitant medications affecting renal function and/or hydration status.

• Thyroid tumors: [US Boxed Warning] Dose-dependent and treatment duration-dependent thyroid C-cell tumors have developed in animal studies with liraglutide therapy; it is unknown whether liraglutide will cause thyroid C-cell tumors, including MTC, in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined. Patients should be counseled on the potential risk of MTC with the use of liraglutide and informed of symptoms of thyroid tumors (eg, neck mass, dysphagia, dyspnea, persistent hoarseness). Use is contraindicated in patients with a personal or a family history of MTC and in patients with multiple endocrine neoplasia syndrome type 2 (MEN2). Cases of MTC in humans have been reported in patients treated with liraglutide. Consultation with an endocrinologist is recommended in patients who develop elevated calcitonin concentrations or have thyroid nodules detected during imaging studies or physical exam. Routine monitoring of serum calcitonin or using thyroid ultrasound monitoring is of uncertain value for early detection of MTC in patients treated with liraglutide.

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 glucagon-like peptide-1 (GLP-1) concentrations (Korner 2009; Peterli 2012). Administration of exogenous GLP-1 agonists may be redundant to surgery effects.

• Gastroparesis: Slows gastric emptying; has not been studied in patients with preexisting gastroparesis.

• Hepatic impairment: Use with caution in patients with hepatic impairment; limited experience.

• Renal impairment: Use with caution in patients with renal impairment, particularly during initiation of therapy and dose escalation.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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: Diabetes mellitus: Victoza is not for use in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis; not a substitute for insulin. Saxenda is not indicated for the treatment of type 2 diabetes; concomitant use with insulin is not recommended.

• Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

In clinical trials liraglutide's pharmacokinetics did not differ between younger and older participants. The manufacturer reports that the safety and efficacy of liraglutide did not differ in older diabetics. Intensive glucose control (HbA_1c <6.5%) has been linked to increased all-cause and cardiovascular mortality, hypoglycemia requiring assistance, and weight gain in adult type 2 diabetes. How "tightly" to control a geriatric patient's blood glucose needs to be individualized. Such a decision should be based on several factors, including the patient's functional and cognitive status, how well he/she recognizes hypoglycemic or hyperglycemic symptoms, and how to respond to them and other disease states. An HbA_1c <7.5% is an acceptable endpoint for a healthy older adult, while <8% is acceptable for frail elderly patients, those with a duration of illness >10 years, or those with comorbid conditions and requiring combination diabetes medications. In patients with advanced microvascular complications and/or a life expectancy <5 years, a target HbA_1c of 8% to 9% is reasonable. For elderly patients with diabetes who are relatively healthy, attaining target goals for aspirin use, blood pressure, lipids, smoking cessation, and diet and exercise may be more important than normalized glycemic control.

Warnings: Additional Pediatric Considerations

May cause hypoglycemia; the risk of hypoglycemia is higher in pediatric patients than adults regardless of concomitant antidiabetic therapy; monitor closely; dosage of insulin may need adjustment. During clinical trials, hypoglycemia (serum glucose <54 mg/dL) was observed in 21.2% of pediatric patients with the addition of liraglutide; no episodes were considered severe; patients on concomitant basal insulin had insulin dose reductions (20%) during liraglutide dose-escalation (Tamborlane 2019). Monitor blood glucose closely, particularly during liraglutide dose titration.

Pregnancy Considerations

Use of liraglutide for chronic weight management is contraindicated in pregnant women (lack of potential benefit and possible fetal harm). An increased risk of adverse maternal and fetal outcomes is associated with obesity; however, medications for weight loss therapy are not recommended at conception or during pregnancy (ACOG 156 2015).

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 birth defects, stillbirth, and macrosomia (ACOG 201 2018). To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA_1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2020; Blumer 2013).

Agents other than liraglutide are currently recommended to treat diabetes in pregnant women (ADA 2020).

Breast-Feeding Considerations

It is not known if liraglutide 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.

Lexicomp Pregnancy & Lactation, In-Depth

• Liraglutide

Briggs' Drugs in Pregnancy & Lactation

• Liraglutide

Adverse Reactions

Obesity:

>10%:

Cardiovascular: Increased heart rate (>10 bpm from baseline: 34%; >20 bpm from baseline: 5%)

Central nervous system: Headache (14%)

Endocrine & metabolic: Hypoglycemia (obesity patients with type 2 diabetics: combination therapy with sulfonylurea: 44%; monotherapy: 16%; nondiabetic patients: 2% to 3%)

Gastrointestinal: Nausea (39%), diarrhea (21%), constipation (19%), vomiting (16%)

Local: Injection site reaction (3% to 14%)

1% to 10%:

Cardiovascular: Tachycardia (6%; one resting heart rate >100 bpm)

Central nervous system: Fatigue (8%), dizziness (7%)

Dermatologic: Injection site pruritus (1% to 3%), rash at injection site (1% to 3%)

Endocrine & metabolic: Altered hormone level (1%; increased serum calcitonin)

Gastrointestinal: Decreased appetite (10%), dyspepsia (10%), abdominal distension (5%), abdominal pain (5%), eructation (5%), gastroenteritis (5%), gastroesophageal reflux disease (5%), upper abdominal pain (5%), increased serum lipase (2% to 5%), flatulence (4%), viral gastroenteritis (3%), cholelithiasis (2%), xerostomia (2%)

Genitourinary: Urinary tract infection (4%)

Immunologic: Antibody development (3%; neutralizing: 1%)

Local: Erythema at injection site (1% to 3%)

Neuromuscular & skeletal: Asthenia (2%)

Type 2 diabetes mellitus: Incidence reported with adult patients in monotherapy trials unless otherwise specified.

>10%:

Central nervous system: Headache (10% to 11%)

Endocrine & metabolic: Hypoglycemia (children and adolescents: 21%)

Gastrointestinal: Gastrointestinal disease (43%), nausea (18% to 20%), diarrhea (10% to 12%)

Infection: Infection (patients with antibodies: 40%)

Respiratory: Upper respiratory tract infection (7%; patients with antibodies: 11%)

1% to 10%:

Dermatologic: Rash at injection site

Gastrointestinal: Decreased appetite (9% to 10%), dyspepsia (combination trials: 9%, monotherapy: 4% to 7%), vomiting (6% to 9%), increased serum lipase (8%), constipation (5%), cholelithiasis (2%), cholecystitis (1%), increased amylase (1%)

Hepatic: Hyperbilirubinemia (monotherapy and combination trials: 4%)

Immunologic: Antibody development (≤9%; neutralizing antibodies: 2%)

Local: Injection site reaction (monotherapy and combination trials: 2%), erythema at injection site

Neuromuscular & skeletal: Back pain (4% to 5%)

Respiratory: Nasopharyngitis (9% to 10%)

<1%, postmarketing, and/or case reports (any indication): Acute pancreatitis, acute renal failure, anaphylaxis, angioedema, asthma, benign gastrointestinal neoplasm (colorectal), bronchospasm, cholecystitis, cholestasis, dehydration, dysgeusia, exacerbation of renal failure, facial edema, first degree atrioventricular block, hemorrhagic pancreatitis, hepatitis, hypersensitivity reaction, increased liver enzymes, increased serum creatinine, increased susceptibility to infection, left bundle branch block, malaise, malignant neoplasm, malignant neoplasm of breast, malignant neoplasm of colon or rectum, medullary thyroid carcinoma, necrotizing pancreatitis, oropharyngeal edema, pancreatitis, papillary thyroid carcinoma, pharyngeal edema, pruritus, right bundle branch block, skin rash, suicidal ideation, systolic hypotension, thyroid disease (C-cell hyperplasia), urticaria

* See Cautions in AHFS Essentials for additional information.

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

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. Exceptions: Danazol. Risk C: Monitor therapy

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

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: Liraglutide may enhance the hypoglycemic effect of Insulins. Management: If liraglutide is used for the treatment of diabetes (Victoza), consider insulin dose reductions. The combination of liraglutide and insulin should be avoided if liraglutide is used exclusively for weight loss (Saxenda). Risk D: Consider therapy modification

Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

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

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

Monitoring Parameters

Plasma glucose, HbA_1c (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 2019]); renal function; signs/symptoms of pancreatitis; triglycerides; signs/symptoms of gallbladder disease; emergence of worsening depression, suicidal thoughts/behavior, changes in behavior; heart rate; body weight (at week 16 when used for chronic weight management)

Reference Range

Recommendations for glycemic control in patients with diabetes (ADA 2019):

Nonpregnant adults:

HbA_1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA_1c goal may be targeted based on patient-specific characteristics).

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: <180 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).

Older adults (≥65 years of age):

HbA_1c: <7.5% (healthy); <8% (complex/intermediate health); <8.5% (very complex/poor health) (individualization may be appropriate based on patient and caregiver preferences).

Preprandial capillary blood glucose: 90 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: 90 to 150 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health).

Advanced Practitioners Physical Assessment/Monitoring

Assess for use-related cautions (eg, renal or hepatic impairment, history of patient or familial medullary thyroid cancer, multiple endocrine neoplasia syndrome type 2 [MEN2]). Teach patient diabetes self-management and proper injection techniques and syringe/needle disposal.

Nursing Physical Assessment/Monitoring

Assess for use-related cautions (eg, renal or hepatic impairment, history of patient or familial medullary thyroid cancer, multiple endocrine neoplasia syndrome type 2 [MEN2]). Teach patient diabetes self-management and proper injection techniques and syringe/needle disposal.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Pen-injector, Subcutaneous:

Saxenda: 18 mg/3 mL (3 mL) [contains phenol, propylene glycol]

Victoza: 18 mg/3 mL (3 mL) [contains phenol, propylene glycol]

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Pen-injector, Subcutaneous:

Saxenda: 18 mg/3 mL (3 mL) [contains phenol, propylene glycol]

Victoza: 6 mg/mL (3 mL) [contains phenol, propylene glycol]

Anatomic Therapeutic Chemical (ATC) Classification

• A10BJ02

Generic Available (US)

No

Pricing: US

Solution Pen-injector (Saxenda Subcutaneous)

18 mg/3 mL (per mL): $103.77

Solution Pen-injector (Victoza Subcutaneous)

18 mg/3 mL (per mL): $129.05

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.

Mechanism of Action

Liraglutide is a long acting analog of human glucagon-like peptide-1 (GLP-1) (an incretin hormone) which increases glucose-dependent insulin secretion, decreases inappropriate glucagon secretion, increases B-cell growth/replication, slows gastric emptying, and decreases food intake. Liraglutide administration results in decreases in hemoglobin A_1c by approximately 1%.

Pharmacodynamics/Kinetics

Note: Pharmacokinetic data in type 2 diabetes mellitus pediatric patients (10 to 17 years) is similar to adult patients.

Distribution: V_d: SubQ: ~13 to 25 L; IV: 0.07 L/kg

Protein binding: >98%

Metabolism: Endogenously metabolized by dipeptidyl peptidase IV (DPP-IV) and endogenous endopeptidases (Croom 2009); metabolism occurs slower than that seen with native GLP-1

Bioavailability: SubQ: ~55%

Half-life, elimination: ~13 hours

Time to peak, plasma: SubQ: 8 to 12 hours

Excretion: Urine (6%, as metabolites); feces (5%, as metabolites)

Pharmacodynamics/Kinetics: Additional Considerations

Body weight: Exposure decreases with an increase in baseline body weight; however, the 1.2 mg and 1.8 mg daily doses of liraglutide provided adequate systemic exposures over the body weight range of 40 to 160 kg.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Schedule type 1 and type 2 diabetic patients for dental treatment in the morning in order to minimize chance of stress-induced hypoglycemia. Occurrence of xerostomia during treatment for obesity (normal salivary flow resumes upon discontinuance). Type 2 diabetes, occurrence of nasopharyngitis; rare occurrence of distortion of the sense of taste (dysgeusia), facial edema, oropharyngeal edema.

Effects on Bleeding

No information available to require special precautions

Related Information

• Injectable Agents (Non-Insulin) for Type 2 Diabetes
• Safe Handling of Hazardous Drugs

Index Terms

NN2211

FDA Approval Date

January 25, 2010

References

<800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 40-NF 35). Rockville, MD: United States Pharmacopeia Convention; 2018:84-103.

American College of Obstetricians and Gynecologists (ACOG). Practice Bulletin No. 201: Pregestational diabetes mellitus. Obstet Gynecol. 2018;132(6):e228-e248. doi: 10.1097/AOG.0000000000002960.[PubMed 30461693]

American College of Obstetricians and Gynecologists (ACOG). Practice Bulletin No 156: Obesity in pregnancy. Obstet Gynecol. 2015;126(6):e112-126. doi: 10.1097/AOG.0000000000001211.[PubMed 26595582]

American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 190: Gestational diabetes mellitus. Obstet Gynecol. 2018;131(2):e49-e64.[PubMed 29370047]

American Diabetes Association (ADA). Standards of medical care in diabetes–2019. Diabetes Care. 2019;42(suppl 1):S1-S193. http://care.diabetesjournals.org/content/42/Supplement_1. Accessed January 24, 2019.

American Diabetes Association (ADA). Standards of medical care in diabetes–2020. Diabetes Care. 2020;43(suppl 1):S1-S212. https://care.diabetesjournals.org/content/43/Supplement_1. Accessed January 22, 2020.

Apovian CM, Aronne LJ, Bessesen DH, et al; Endocrine Society. Pharmacological management of obesity: an Endocrine Society clinical practice guideline [published correction appears in J Clin Endocrinol Metab. 2015;100(5):2135-2136]. J Clin Endocrinol Metab. 2015;100(2):342-362. doi: 10.1210/jc.2014-3415.[PubMed 25590212]

Blumer I, Hadar E, Hadden DR, et al. Diabetes and pregnancy: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(11):4227-4249.[PubMed 24194617]

Bray GA, Heisel WE, Afshin A, et al. The science of obesity management: an Endocrine Society scientific statement. Endocr Rev. 2018;39(2):79-132. doi: 10.1210/er.2017-00253.[PubMed 29518206]

Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Can J Diabetes. 2013;35(suppl 1):1-212.

Centers for Disease Control and Prevention (CDC). CDC clinical reminder: insulin pens must never be used for more than one person. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/injectionsafety/clinical-reminders/insulin-pens.html. Updated January 5, 2012. Accessed January 9, 2012.

Croom KF, McCormack PL. Liraglutide: A Review of Its Use in Type 2 Diabetes Mellitus. Drugs. 2009;69(14):1985-2004.[PubMed 19747013]

Danne T, Biester T, Kapitzke K, et al. Liraglutide in an Adolescent Population with Obesity: A Randomized, Double-Blind, Placebo-Controlled 5-Week Trial to Assess Safety, Tolerability, and Pharmacokinetics of Liraglutide in Adolescents Aged 12-17 Years. J Pediatr. 2017;181:146-153.e3. doi: 10.1016/j.jpeds.2016.10.076.[PubMed 27979579]

Das SR, Everett BM, Birtcher KK, et al. 2018 ACC expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. 2018;72(24):3200-3223. doi: 10.1016/j.jacc.2018.09.020.[PubMed 30497881]

Dungan K, DeSaintis A. Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes mellitus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 25, 2019.

Faillie JL, Yu OH, Yin H, et al. Association of bile duct and gallbladder diseases with the use of incretin-based drugs in patients with type 2 diabetes mellitus. JAMA Intern Med. 2016;176(10):1474-1481.[PubMed 27478902]

Fox CK, Gross AC, Bomberg EM, et al. Severe Obesity in the Pediatric Population: Current Concepts in Clinical Care [published online May 3, 2019]. Curr Obes Rep. doi: 10.1007/s13679-019-00347-z.[PubMed 31054014]

Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE obesity clinical practice guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22(suppl 3):1-203. doi: 10.4158/EP161365.GL.[PubMed 27219496]

Korner J, Inabnet W, Febres G, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond). 2009;33(7):786-795. doi: 10.1038/ijo.2009.79.[PubMed 19417773]

Marso SP, Daniels GH, Brown-Frandsen K, et al; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311-322. doi: 10.1056/NEJMoa1603827.[PubMed 27295427]

Mastrandrea LD, Witten L, Carlsson Petri KC, Hale PM, Hedman HK, Riesenberg RA. Liraglutide effects in a paediatric (7-11 y) population with obesity: A randomized, double-blind, placebo-controlled, short-term trial to assess safety, tolerability, pharmacokinetics, and pharmacodynamics. Pediatr Obes. 2019;14(5):e12495. doi: 10.1111/ijpo.12495.[PubMed 30653847]

Mechanick JI, Youdim A, Jones DB, et al. Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient--2013 update: cosponsored by American Association of Clinical Endocrinologists, the Obesity Society, and American Society for Metabolic & Bariatric Surgery. Surg Obes Relat Dis. 2013;9(2):159-191. doi: 10.1016/j.soard.2012.12.010.[PubMed 23537696]

Nauck MA, Kahle M, Baranov O, Deacon CF, Holst JJ. Addition of a dipeptidyl peptidase-4 inhibitor, sitagliptin, to ongoing therapy with the glucagon-like peptide-1 receptor agonist liraglutide: A randomized controlled trial in patients with type 2 diabetes. Diabetes Obes Metab. 2017;19(2):200-207. doi: 10.1111/dom.12802.[PubMed 27709794]

Perreault L. Obesity in adults: Drug therapy. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 10, 2019.

Peterli R, Steinert RE, Woelnerhanssen B, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg. 2012;22(5):740-748. doi: 10.1007/s11695-012-0622-3.[PubMed 22354457]

Saxenda (liraglutide) [prescribing information]. Plainsboro, NJ: Novo Nordisk; November 2018.

Saxenda (liraglutide) [product monograph]. Mississauga, Ontario, Canada: Novo Nordisk Canada Inc; July 2017.

Srivastava G, Fox CK, Kelly AS, et al. Clinical considerations regarding the use of obesity pharmacotherapy in adolescents with obesity. Obesity (Silver Spring). 2019;27(2):190-204. doi: 10.1002/oby.22385.[PubMed 30677262]

Tamborlane WV, Barrientos-Pérez M, Fainberg U, et al; Ellipse Trial Investigators. Liraglutide in children and adolescents with type 2 diabetes [published online April 28, 2019]. N Engl J Med. doi: 10.1056/NEJMoa1903822.[PubMed 31034184]

US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/. Updated September 2016. Accessed October 30, 2019.

Victoza (liraglutide) [prescribing information]. Plainsboro, NJ: Novo Nordisk Inc; June 2019.

Victoza (liraglutide) [product monograph]. Mississauga, Ontario, Canada: Novo Nordisk Canada Inc; November 2017.

Wexler DJ. Initial management of blood glucose in adults with type 2 diabetes mellitus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 25, 2019.

Brand Names: International

Saxenda (AU, BE, BH, CZ, EE, HK, HR, IE, IL, LB, LT, MY, NL, PH, PT, SE, SG); Victoza (AE, AR, AT, AU, BB, BE, BH, BR, CH, CL, CN, CR, CU, CY, CZ, DE, DK, DO, EE, ES, FR, GB, GT, HK, HN, HR, HU, ID, IE, IL, IN, IS, JO, JP, KR, KW, LB, LK, LT, LU, LV, MT, MY, NI, NL, NO, PA, PH, PL, PT, QA, RO, RU, SA, SE, SG, SI, SK, SV, TH, TR, UA)

Last Updated 2/20/20