Saxenda

— THERAPEUTIC CATEGORIES —
  • Obesity
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Saxenda Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Liraglutide 6mg/mL; soln for SC inj.

    Pharmacological Class

    Glucagon-like peptide-1 (GLP-1) receptor agonist.

    How Supplied

    Multi-dose, pre-filled pen (3mL)—3, 5

    How Supplied

    Saxenda injection: 6 mg/mL in a 3 mL single-patient-use pre-filled pen (delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3 mg) is available in the following package sizes: 

    • 3 x Saxenda pen 

    • 5 x Saxenda pen

    Storage

    Prior to first use:

    • Saxenda should be stored in a refrigerator between 36º F to 46º F (2º C to 8º C). Do not store in the freezer or directly adjacent to the refrigerator cooling element. Do not freeze Saxenda and do not use Saxenda if it has been frozen. 

    After initial use:

    • The Saxenda pen can be stored for 30 days at controlled room temperature (59° F to 86° F; 15° C to 30° C) or in a refrigerator (36° F to 46° F; 2° C to 8° C). Keep the pen cap on when not in use. Protect Saxenda from excessive heat and sunlight. 

    Manufacturer

    Novo Nordisk

    Generic Availability

    NO

    Saxenda Indications

    Indications

    Adjunct to reduced-calorie diet and increased physical activity for chronic weight management: in adults with an initial BMI of ≥30kg/m2 (obese), or ≥27kg/m2 (overweight) in the presence of at least one weight-related comorbid condition (eg, hypertension, T2DM, dyslipidemia); in children aged ≥12yrs with body weight ≥60kg and an initial BMI corresponding to ≥30kg/m2 for adults (obese) by international cut-offs.

    Limitations of Use

    Do not use with other liraglutide-containing products or GLP-1 receptor agonists. Safety and efficacy in children with T2DM or with concomitant other weight loss products (including prescription or OTC drugs, herbal preps) have not been established.

    Limitations of Use Expanded

    Saxenda contains liraglutide and should not be coadministered with other liraglutide-containing products or with any other GLP-1 receptor agonist. 

    The safety and effectiveness of Saxenda in pediatric patients with type 2 diabetes have not been established. 

    The safety and efficacy of Saxenda in combination with other products intended for weight loss have not been established.

    Saxenda Dosage and Administration

    Adult

    Give by SC inj into abdomen, thigh, or upper arm once daily. Escalate dose with the following schedule (to mitigate risk of GI effects): Week 1: 0.6mg daily; Week 2: 1.2mg daily; Week 3: 1.8mg daily; Week 4: 2.4mg daily; Week 5 and onward: 3mg daily (recommended dose). Delay dose escalation 1 week if increased dose not tolerated; discontinue if 3mg not tolerated. If concurrent insulin secretagogues (eg, sulfonylureas) or insulin; consider reducing their doses by ½. If >3 days elapsed since last dose, reinitiate at 0.6mg/day, then follow dose escalation schedule. Evaluate response after 16 weeks. Discontinue if ≥4% weight loss is not achieved.

    Children

    <12yrs: not established. Give by SC inj into abdomen, thigh, or upper arm once daily. ≥12yrs: escalate dose with the following schedule (to mitigate risk of GI effects): Week 1: 0.6mg daily; Week 2: 1.2mg daily; Week 3: 1.8mg daily; Week 4: 2.4mg daily; Week 5 and onward: 3mg daily (recommended dose). Lower escalation dose to previous level if increased dose not tolerated; dose escalation may take up to 8wks. Reduce maintenance dose to 2.4mg daily if 3mg not tolerated; discontinue if 2.4mg not tolerated. If >3 days elapsed since last dose, reinitiate at 0.6mg/day, then follow dose escalation schedule. Evaluate response after 12 weeks. Discontinue if ≥1% weight loss is not achieved.

    Renal Impairment

    There is limited experience with Saxenda in patients with mild, moderate, and severe renal impairment, including end-stage renal disease. However, there have been postmarketing reports of acute renal failure and worsening of chronic renal failure with liraglutide, which may sometimes require hemodialysis. Saxenda should be used with caution in this patient population.

    Hepatic Impairment

    There is limited experience in patients with mild, moderate, or severe hepatic impairment. Therefore, Saxenda should be used with caution in this patient population.

    Saxenda Contraindications

    Contraindications

    History (personal or family) of medullary thyroid carcinoma (MTC). Multiple endocrine neoplasia syndrome type 2 (MEN 2). Pregnancy.

    Saxenda Boxed Warnings

    Boxed Warning

    Risk of thyroid C-cell tumors.

    Boxed Warning

    Risk of thyroid C-cell tumors

    • Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Saxenda causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.

    • Saxenda is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). 

    Saxenda Warnings/Precautions

    Warnings/Precautions

    Risk of thyroid C-cell tumors; inform patients of potential risk and symptoms. Monitor for pancreatitis; discontinue if suspected; do not restart if confirmed. Risk of acute gallbladder disease. History of suicidal attempts or ideation: avoid. Monitor for emergence or worsening depression, suicidal thinking or behavior; discontinue if occurs. Monitor blood glucose prior to and during treatment in type 2 diabetics. Monitor heart rate periodically; discontinue if sustained increases. History of anaphylaxis or angioedema with other GLP-1 receptor agonist. Discontinue if hypersensitivity reactions occur. Renal impairment: caution with initiating or escalating doses. Hepatic impairment. Gastroparesis: not studied. Nursing mothers.

    Warnings/Precautions

    Risk of Thyroid C-cell Tumors 

    Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors (adenomas and/or carcinomas) at clinically relevant exposures in both genders of rats and mice. Malignant thyroid C-cell carcinomas were detected in rats and mice. It is unknown whether Saxenda will cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.

    Acute Pancreatitis 

    Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with liraglutide. After initiation of Saxenda, observe patients for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, Saxenda should promptly be discontinued and appropriate management should be initiated. If pancreatitis is confirmed, Saxenda should not be restarted.

    Liraglutide has been studied in a limited number of adult patients with a history of pancreatitis. It is unknown if patients with a history of pancreatitis are at higher risk for development of pancreatitis on Saxenda.

    Acute Gallbladder Disease

    If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.

    Hypoglycemia

    Adult patients with type 2 diabetes mellitus on an insulin secretagogue (eg, sulfonylurea) or insulin may have an increased risk of hypoglycemia with use of Saxenda, including severe hypoglycemia. In patients with type 2 diabetes, monitor blood glucose prior to starting and during Saxenda treatment.

    Heart Rate Increase 

    Mean increases in resting heart rate of 2 to 3 beats per minute (bpm) were observed with routine clinical monitoring in Saxenda-treated adult patients compared to placebo in clinical trials. Heart rate should be monitored at regular intervals consistent with usual clinical practice. For patients who experience a sustained increase in resting heart rate while taking Saxenda, Saxenda should be discontinued.

    Renal Impairment

    In patients treated with GLP-1 receptor agonists, including Saxenda, there have been reports of acute renal failure and worsening of chronic renal failure, sometimes requiring hemodialysis. Some of these events were reported in patients without known underlying renal disease. Use caution when initiating or escalating doses of Saxenda in patients with renal impairment.

    Hypersensitivity Reactions 

    Serious hypersensitivity reactions (eg, anaphylactic reactions, angioedema) in patients treated with Saxenda have been reported. If a hypersensitivity reaction occurs, the patient should discontinue Saxenda and other suspect medications and promptly seek medical advice. Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists. Use caution in a patient with a history of anaphylaxis or angioedema with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to these reactions with Saxenda.

    Suicidal Behavior and Ideation

    Patients treated with Saxenda should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue Saxenda in patients who experience suicidal thoughts or behaviors. Avoid Saxenda in patients with a history of suicidal attempts or active suicidal ideation.

    Pregnancy Considerations

    Saxenda is contraindicated during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm. There are no available data with liraglutide in pregnant women to inform a drug associated risk for major birth defects and miscarriage. Saxenda should not be used during pregnancy. If a patient wishes to become pregnant, or pregnancy occurs, treatment with Saxenda should be discontinued.

    Nursing Mother Considerations

    There are no data on the presence of liraglutide in human milk, the effects on the breastfed infant, or effects on milk production. Liraglutide was present in the milk of lactating rats. 

    The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for liraglutide and any potential adverse effects on the breastfed infant from liraglutide or from the underlying maternal condition.

    Pediatric Considerations

    The safety and effectiveness of liraglutide have not been established in patients <12 years of age.

    Geriatric Considerations

    In the Saxenda clinical trials, 232 (6.9%) of the Saxenda-treated patients were ≥65 years of age, and 17 (0.5%) of the Saxenda-treated patients were ≥75 years of age. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

    Renal Impairment Considerations

    There is limited experience with Saxenda in patients with mild, moderate, and severe renal impairment, including end-stage renal disease. However, there have been postmarketing reports of acute renal failure and worsening of chronic renal failure with liraglutide, which may sometimes require hemodialysis. Saxenda should be used with caution in this patient population.

    Hepatic Impairment Considerations

    There is limited experience in patients with mild, moderate, or severe hepatic impairment. Therefore, Saxenda should be used with caution in this patient population.

    Other Considerations for Specific Populations

    Saxenda slows gastric emptying. Saxenda has not been studied in patients with pre-existing gastroparesis.

    Saxenda Pharmacokinetics

    Absorption

    Following subcutaneous administration, maximum concentrations of liraglutide are achieved at 11 hours post dosing. The average liraglutide steady state concentration (AUCτ/24) reached ~116 ng/mL in obese (BMI 30-40 kg/m2) patients after Saxenda administration. Absolute bioavailability of liraglutide following subcutaneous administration is ~55%.

    Distribution

    Liraglutide is extensively bound to plasma protein (>98%).

    Metabolism

    Liraglutide is endogenously metabolized in a similar manner to large proteins without a specific organ as a major route of elimination.

    Elimination

    Following a [3H]-liraglutide dose, intact liraglutide was not detected in urine or feces. Only a minor part of the administered radioactivity was excreted as liraglutide-related metabolites in urine or feces (6% and 5%, respectively). The mean apparent clearance following subcutaneous administration of a single dose of liraglutide is ~0.9-1.4 L/h with an elimination half-life of ~13 hours, making liraglutide suitable for once daily administration.

    Saxenda Interactions

    Interactions

    Increased risk of hypoglycemia with concomitant insulin secretagogues (eg, sulfonylureas) or insulin; may need a lower dose of these (see Adults); monitor. May affect absorption of other oral drugs (delayed gastric emptying).

    Interactions

    Saxenda causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. Monitor for potential consequences of delayed absorption of oral medications concomitantly administered with Saxenda.

    Increased risk of hypoglycemia with concomitant insulin secretagogues (eg, sulfonylurea) or insulin. The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin.

    Saxenda Adverse Reactions

    Adverse Reactions

    Nausea, diarrhea, constipation, vomiting, inj site reactions, headache, hypoglycemia, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase, pyrexia, gastroenteritis; hypersensitivity reactions.

    Saxenda Clinical Trials

    Clinical Trials

    Weight Management Trials in Adults with Overweight or Obesity 

    The safety and efficacy of Saxenda for chronic weight management in conjunction with reduced caloric intake and increased physical activity were studied in three 56-week, randomized, double-blind, placebo-controlled trials. In all studies, Saxenda was titrated to 3 mg daily during a 4-week period.

    • Study 1 enrolled 3731 patients with obesity (BMI ≥30 kg/m2) or with overweight (BMI 27-29.9 kg/m2) and at least one weight-related comorbid condition such as treated or untreated dyslipidemia or hypertension; patients with type 2 diabetes mellitus were excluded. Patients were randomized in a 2:1 ratio to either Saxenda or placebo. Patients were stratified based on the presence or absence of abnormal blood glucose measurements at randomization. All patients were treated for up to 56 weeks. Those patients with abnormal glucose measurements at randomization (2254 of the 3731 patients) were treated for a total of 160 weeks. Mean baseline body weight was 106.3 kg and mean BMI was 38.3 kg/m2.
    • Study 2 was a 56-week trial that enrolled 635 patients with type 2 diabetes and with either overweight or obesity (as defined above). Patients were to have an HbA1c of 7-10% and be treated with metformin, a sulfonylurea, or a glitazone as single agent or in any combination, or with a reduced-calorie diet and physical activity alone. Patients were randomized in a 2:1 ratio to receive either Saxenda or placebo. Mean baseline body weight was 105.9 kg and mean BMI was 37.1 kg/m2. 
    • Study 3 was a 56-week trial that enrolled 422 patients with obesity (BMI ≥30 kg/m2) or with overweight (BMI 27-29.9 kg/m2) and at least one weight-related comorbid condition such as treated or untreated dyslipidemia or hypertension; patients with type 2 diabetes mellitus were excluded. All patients were first treated with a low-calorie diet (total energy intake 1200-1400 kcal/day) in a run-in period lasting up to 12 weeks. Patients who lost at least 5% of their screening body weight after 4 to 12 weeks during the run-in were then randomized, with equal allocation, to receive either Saxenda or placebo for 56 weeks. Mean baseline body weight was 99.6 kg and mean BMI was 35.6 kg/m2.

    For Study 1 and Study 2, the primary efficacy parameters were mean percent change in body weight and the percentages of patients achieving ≥5% and ≥10% weight loss from baseline to week 56. For Study 3, the primary efficacy parameters were mean percent change in body weight from randomization to week 56, the percentage of patients not gaining more than 0.5% body weight from randomization (eg, after run-in) to week 56, and the percentage of patients achieving ≥5% weight loss from randomization to week 56. Because losing at least 5% of fasting body weight through lifestyle intervention during the 4- to 12-week run-in was a condition for their continued participation in the randomized treatment period, the results may not reflect those expected in the general population.

    After 56 weeks, treatment with Saxenda resulted in a statistically significant reduction in weight compared with placebo. Statistically significantly greater proportions of patients treated with Saxenda achieved 5% and 10% weight loss than those treated with placebo. In Study 3, statistically significantly more patients randomized to Saxenda than placebo had not gained more than 0.5% of body weight from randomization to week 56. The following are the results observed in Studies 1, 2, and 3 at week 56 for treatment with Saxenda vs placebo, respectively:

    • Study 1 (Obesity or overweight with comorbidity)
      • Weight percent change from baseline:  -7.4 vs -3.0; difference from placebo:  -4.5 (95% CI, -5.2, -3.8; P <.0001)
      • % of patients losing ≥5% body weight:  62.3% vs 34.4%; difference from placebo:  27.9 (95% CI, 23.9-31.9; P <.0001)
      • % of patients losing >10% body weight:  33.9% vs 15.4%; difference from placebo:  18.5 (95% CI, 15.2-21.7; P <.0001)
    • Study 2 (Type 2 diabetes with obesity or overweight)
      • Weight percent change from baseline:  -5.4 vs -1.7; difference from placebo:  -3.7 (95% CI, -4.7, -2.7; P <.0001)
      • % of patients losing ≥5% body weight:  49.0% vs 16.4%; difference from placebo:  32.6 (95% CI, 25.1-40.1; P <.0001)
      • % of patients losing >10% body weight:  22.4% vs 5.5%; difference from placebo:  16.9 (95% CI, 11.7-22.1; P <.0001)
    • Study 3 (Obesity or overweight with comorbidity following at least 5% weight loss with diet)
      • Weight percent change from baseline:  -4.9 vs -0.3; difference from placebo:  -5.2 (95% CI, -6.8, -3.5; P <.0001)
      • % of patients losing ≥5% body weight:  44.2% vs 21.7%; difference from placebo:  22.6 (95% CI, 13.9-31.3; P <.0001)
      • % of patients losing >10% body weight:  25.4% vs 6.9%; difference from placebo:  18.5 (95% CI, 11.7-25.3; P <.0001)

     

    Weight Management Trial in Pediatric Patients Ages 12 and Older with Obesity 

    Saxenda was evaluated in a 56-week, double-blind, randomized, parallel group, placebo controlled multicenter trial in 251 pubertal pediatric patients aged 12 to 17 years, with BMI corresponding to 30 kg/m2 or greater for adults by international cut-off points and BMI of 95th percentile or greater for age and sex. After a 12-week lifestyle run-in period, patients were randomized 1:1 to Saxenda once-daily or placebo once-daily. The Saxenda dose was titrated to 3 mg over a 4- to 8-week period based on tolerability as judged by the investigator. Escalation of the trial product was not allowed if the subject had a self-monitored plasma glucose (SMPG) < 56 mg/dL or < 70 mg/dL in the presence of symptoms of hypoglycemia during the week prior to or during the dose escalation visits. The proportion of patients who reached the 3 mg dose was 82.4%; for 8.8% of patients 2.4 mg was the maximum tolerated dose.

    The primary endpoint was change in BMI SDS. At baseline, mean BMI SDS was 3.14 in the Saxenda group and 3.20 in the placebo group. At week 56, treatment with Saxenda resulted in statistically significant reduction in BMI SDS from baseline compared to placebo. The observed mean change in BMI SDS from baseline to week 56 was -0.23 in the Saxenda group and -0.00 in the placebo group. The estimated treatment difference in BMI SDS reduction from baseline between Saxenda and placebo was -0.22 with a 95% confidence interval of -0.37, -0.08; P =0.0022.

    For more clinical trial data, see full labeling.

    Saxenda Note

    Not Applicable

    Saxenda Patient Counseling

    Patient Counseling

    Instructions 

    Advise patients to take Saxenda exactly as prescribed. Instruct patients to follow the dose escalation schedule and to not take more than the recommended dose. 

    Instruct adult patients to discontinue Saxenda if they have not achieved 4% weight loss by 16 weeks of treatment. Instruct pediatric patients 12 years of age and older to discontinue Saxenda if they have not achieved a BMI reduction of 1% from baseline after 12 weeks on the maintenance dose. 

    Risk of Thyroid C-cell Tumors 

    Inform patients that liraglutide causes benign and malignant thyroid C-cell tumors in mice and rats and that the human relevance of this finding has not been determined. Counsel patients to report symptoms of thyroid tumors (eg, a lump in the neck, hoarseness, dysphagia or dyspnea) to their health care provider. 

    Acute Pancreatitis 

    Inform patients of the potential risk for acute pancreatitis. Explain that persistent severe abdominal pain that may radiate to the back which may or may not be accompanied by vomiting is the hallmark symptom of acute pancreatitis. Instruct patients to discontinue Saxenda promptly and contact their health care provider if persistent severe abdominal pain occurs. 

    Acute Gallbladder Disease 

    Inform patients of the risk of acute gallbladder disease. Advise patients that substantial or rapid weight loss can increase the risk of gallbladder disease, but that gallbladder disease may also occur in the absence of substantial or rapid weight loss. Instruct patients to contact their healthcare provider for appropriate clinical follow-up if gallbladder disease is suspected.

    Hypoglycemia 

    Inform pediatric patients of the risk of hypoglycemia and educate all patients on the signs and symptoms of hypoglycemia. Inform adult patients with type 2 diabetes mellitus on an insulin secretagogue (eg, sulfonylurea) or insulin that they may have an increased risk of hypoglycemia when using Saxenda and to report signs and/or symptoms of hypoglycemia to their healthcare provider. 

    Heart Rate Increase 

    Inform patients to report symptoms of sustained periods of heart pounding or racing while at rest to their healthcare provider. Discontinue Saxenda in patients who experience a sustained increase in resting heart rate.

    Dehydration and Renal Impairment 

    Advise patients of the risk of dehydration due to gastrointestinal adverse reactions and to take precautions to avoid fluid depletion. Inform patients of the potential risk for worsening renal function, which in some cases may require dialysis.

    Hypersensitivity Reactions 

    Inform patients that serious hypersensitivity reactions have been reported during postmarketing use of Saxenda. Advise patients on the symptoms of hypersensitivity reactions and instruct them to stop taking Saxenda and seek medical advice promptly if such symptoms occur. 

    Suicidal Behavior and Ideation 

    Advise patients to report emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Inform patients that if they experience suicidal thoughts or behaviors, they should stop taking Saxenda. 

    Jaundice and Hepatitis 

    Inform patients that jaundice and hepatitis have been reported during postmarketing use of liraglutide. Instruct patients to contact their healthcare provider if they develop jaundice. 

    Never Share a Saxenda Pen Between Patients 

    Inform patients that they should never share a Saxenda pen with another person, even if the needle is changed. Sharing of the pen between patients may pose a risk of transmission of infection.

    Cost Savings Program

    The Saxenda savings program is available here.

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