Side effects of victoza

Victoza Side Effects

Generic Name: liraglutide

Medically reviewed by Drugs.com. Last updated on Nov 26, 2018.

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Note: This document contains side effect information about liraglutide. Some of the dosage forms listed on this page may not apply to the brand name Victoza.

For the Consumer

Applies to liraglutide: subcutaneous solution

Warning

Subcutaneous route (Solution)

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 liraglutide 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.Liraglutide 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 for MTC with the use of liraglutide and inform them of symptoms of thyroid tumors (eg a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with liraglutide.

Along with its needed effects, liraglutide (the active ingredient contained in Victoza) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking liraglutide:

More common

  • Bladder pain
  • bloody or cloudy urine
  • chills
  • cough
  • diarrhea
  • difficult, burning, or painful urination
  • fever
  • frequent urge to urinate
  • general feeling of discomfort or illness
  • headache
  • hoarseness
  • joint pain
  • loss of appetite
  • lower back or side pain
  • muscle aches and pains
  • nausea
  • runny nose
  • shivering
  • sore throat
  • sweating
  • trouble sleeping
  • unusual tiredness or weakness
  • vomiting

Less common

  • Blurred vision
  • dizziness
  • nervousness
  • pounding in the ears
  • slow or fast heartbeat

Rare

  • Anxiety
  • cold sweats
  • confusion
  • cool, pale skin
  • depression
  • hives or welts, itching, or skin rash
  • increased hunger
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • loss of consciousness
  • nightmares
  • redness of the skin
  • seizures
  • shakiness
  • slurred speech

Incidence not known

  • Agitation
  • clay-colored stools
  • confusion
  • dark urine
  • decreased awareness or responsiveness
  • decreased urine output
  • depression
  • difficulty with swallowing
  • hostility
  • irritability
  • muscle twitching
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • rapid weight gain
  • severe sleepiness
  • swelling of the face, ankles, or hands
  • tightness in the chest
  • unpleasant breath odor
  • vomiting of blood
  • yellow eyes or skin

Some side effects of liraglutide may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  • Back pain
  • belching
  • body aches or pain
  • constipation
  • decreased appetite
  • heartburn
  • indigestion
  • loss of voice
  • pain or tenderness around the eyes and cheekbones
  • sneezing
  • stomach cramps, discomfort, or pain
  • stuffy nose
  • swollen mouth and tongue
  • unpleasant taste
  • urge to have bowel movement
  • weight loss

Less common

For Healthcare Professionals

Applies to liraglutide: subcutaneous solution

Gastrointestinal

Chronic Weight Management:

Very common (10% or more): Nausea (39.3%), diarrhea (20.9%), constipation (19.4%), vomiting (15.7%),

Common (1% to 10%): Dyspepsia, abdominal pain, upper abdominal pain, gastroesophageal reflux disease, abdominal distension, eructation, flatulence, dry mouth, gastroenteritis, viral gastroenteritis, increased lipase

Uncommon (0.1% to 1%): Acute pancreatitis, acute gallbladder disease

Type 2 Diabetes Mellitus:

Very common (10% or more): Nausea (up to 28.4%), diarrhea (up to 17.1%), vomiting (up to 10.9%)

Rare (less than 0.1%): Intestinal obstruction

Postmarketing reports: Acute hemorrhagic or necrotizing pancreatitis, including fatalities

Chronic Weight Management:

-The percentage of patients reporting nausea declined as treatment continued. Most gastrointestinal events were mild or moderate and did not lead to discontinuation.

-Acute pancreatitis occurred in 0.3% (9/3291) of liraglutide-treated patients and 0.1% (1/1843) of placebo patients in clinical trials. Three additional cases occurred in liraglutide-treated patients, 2 in patients who prematurely withdrew from the trial and 1 during an off-treatment follow-up period.

-Acute gallbladder disease was reported more frequently in liraglutide-treated patients (1.5% versus 0.5%) during clinical trials. Substantial or rapid weight loss can increase the risk of cholelithiasis, but even after accounting for the degree of weight loss, the incidence of acute gallbladder disease was greater in liraglutide-treated patients.

Type 2 Diabetes Mellitus

-Postmarketing reports of acute hemorrhagic or necrotizing pancreatitis, including fatalities have been reported. During clinical trials, 13 cases of pancreatitis were received among liraglutide treated patients, 9 acute and 4 chronic compared with 1 case in the comparator (glimepiride) group; some patients had other risk factors for pancreatitis, such as a history of cholelithiasis or alcohol abuse.

-Serum amylase and lipase were routinely measure in the LEADER trial; elevations of 3 times the upper limit of normal were reported in 1% and 7.5% of liraglutide treated patients compared with 0.7 % and 4.5% of placebo, respectively.

-In the LEADER trial, 3.1% of liraglutide treated patients reported an acute event of gallbladder disease such as cholelithiasis or cholecystitis.

Metabolic

Chronic Weight Management:

Very common (10% or more): Hypoglycemia in type 2 diabetes (23%)

Common (1% to 10%): Decreased appetite

Type 2 Diabetes Mellitus:

Very common (10% or more): Hypoglycemia (when used in combination with a sulfonylurea)

Common (1% to 10%): Hypoglycemia, anorexia, decreased appetite

Uncommon (0.1% to 1%): Dehydration

Postmarketing reports: Dehydration resulting from nausea, vomiting and diarrhea

Chronic Weight Management:

In patients with type 2 diabetes mellitus receiving this drug for chronic weight management, severe hypoglycemia occurred in 0.7% (3/422) of liraglutide-treated patients, each of these patients was also receiving a sulfonylurea. Among all patients receiving this drug in combination with a sulfonylurea, symptomatic hypoglycemia occurred in 43.6% (48/110) of patients. The dose of sulfonylurea had been reduced by 50% at the start of the trial. Among patients not taking a sulfonylurea, symptomatic hypoglycemia occurred in 15.7% (49/312) of patients.

Type 2 Diabetes Mellitus:

Major episodes of hypoglycemia have not been reported in clinical trials in which liraglutide was used as monotherapy, however, when used in combination with a sulfonylurea, hypoglycemia was very commonly reported.

Nervous system

Very common (10% or more): Headache (up to 13.6%)

Common (1% to 10%): Dizziness

Frequency not reported: dysgeusia

Respiratory

Type 2 Diabetes Mellitus:

Common (1% to 10%): Nasopharyngitis, bronchitis, upper respiratory infection

General

The most commonly reported adverse events for this drug when used for weight management have included nausea, hypoglycemia, diarrhea, constipation, vomiting, headache, decreased appetite, dyspepsia, fatigue, dizziness, abdominal pain, and increased lipase.

The most commonly reported adverse events for this drug when used to treat type 2 diabetes mellitus have included nausea, diarrhea, vomiting, constipation, dyspepsia, and decreased appetite.

Cardiovascular

Chronic Weight Management:

Very common (10% or more): Increases in mean resting heart rate

Common (1% to 10%): Hypotension

Uncommon (0.1% to 1%): Cardiac conduction disorder, tachycardia

Type 2 Diabetes Mellitus:

Common (1% to 10%): Increased heart rate

Chronic Weight Management:

Cardiac conduction disorders were reported as first degree atrioventricular block, right bundle branch block, or left bundle branch block.

Increases in mean resting heart rate of 2 to 3 beats per minute (bpm) were observed in clinical trials. Increases of 10 and 20 bpm at 2 consecutive visits were 34% and 5% in liraglutide-treated patients versus 19% and 2% in the placebo group, respectively. Resting heart rate exceeding 100 bpm was recorded for 6% of liraglutide-treated patients versus 4% of placebo patients. Tachycardia was reported in 0.6% of liraglutide-treated patients compared with 0.1% of placebo patients. Monitoring heart rate over 24-hours found that liraglutide treatment was associated with a 4 to 9 bpm higher heart rate than placebo. The clinical significance of this is unknown.

Genitourinary

Common (1% to 10%): Urinary tract infection

Local

Common (1% to 10%): Injection site erythema, injection site reaction

The most common injection site reactions were erythema, pruritus, and rash at the injection site.

Immunologic

Frequency not reported: Development of anti-liraglutide (the active ingredient contained in Victoza) antibodies

Hypersensitivity

Uncommon (0.1% to 1%): Urticaria

Postmarketing reports: Serious hypersensitivity reactions (e.g. anaphylactic reactions and angioedema), allergic reactions (rash and pruritus)

Renal

While this drug has not been found to be directly nephrotoxic in animal studies or clinical trials, postmarketing reports of acute renal failure and worsening of chronic renal failure sometimes requiring dialysis have been received. A majority of reports occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration.

Type 2 Diabetes Mellitus:

Uncommon (0.1% to 1%): Renal impairment, acute renal failure

Postmarketing reports: Acute renal failure and worsening of chronic renal failure, sometimes requiring dialysis, increased serum creatinine

Dermatologic

Common (1% to 10%): Rash

Uncommon (0.1% to 1%): Urticaria, pruritus

Endocrine

Common (1% to 10%): Increased blood calcitonin levels

Uncommon (0.1% to 1%): Goiter

Other

Common (1% to 10%): Fatigue

Uncommon (0.1% to 1%): Asthenia, malaise

Chronic Weight Management:

Fatigue and asthenia were most commonly reported within the first 12 weeks and were often co-reported with gastrointestinal events.

Psychiatric

Chronic Weight Management:

In clinical trials, 0.2% (6/3384) patients receiving liraglutide (the active ingredient contained in Victoza) reported suicidal ideation and 1 attempted suicide. There were no reports in patients receiving placebo.

Chronic Weight Management:

Common (1% to 10%): Insomnia, anxiety

Uncommon (0.1% to 1%): Suicidal ideation

Very rare (less than 0.01%): Suicide attempt

Hepatic

Chronic Weight Management:

Uncommon (0.1% to 1%): ALT increased

Frequency not reported: AST increased

Type 2 Diabetes Mellitus:

Postmarketing reports: Elevations of liver enzymes, hyperbilirubinemia, cholestasis, hepatitis

Oncologic

Chronic Weight Management:

Breast Cancer: During clinical trials, 0.6% (4/2379) of liraglutide-treated patients were diagnosed with breast cancer compared with 0.2% (3/1300) of placebo patients. There were too few cases to determine if these were related to drug treatment and insufficient data to determine whether this drug had an effect on preexisting breast neoplasia.

Papillary Thyroid Cancer: During clinical trials, 0.2% (7/3291) of the liraglutide-treated patients were diagnosed with papillary thyroid carcinoma compared with no cases in 1843 placebo patients.

Colorectal Neoplasms: During clinical trials, 0.5% (17/3291) of the liraglutide-treated patients had benign colorectal neoplasms compared with 0.2% (4/1843) of placebo patients. Malignant colorectal carcinoma was diagnosed in 2 liraglutide-treated patients.

Type 2 Diabetes Mellitus:

In clinical trials, 6 cases of thyroid C-cell hyperplasia were reported among liraglutide-treated patients and 2 cases in the comparator-treated group (1.3 vs 1 case per 1000 patient-years). Medullary thyroid carcinoma was diagnosed in 1 patient in the comparator group who had pretreatment serum calcitonin concentrations greater than 1000 ng/L suggesting preexisting disease. The study required protocol-specified serum calcitonin measurements. All cases of thyroid C-cell hyperplasia were diagnosed after thyroidectomy which was done due to abnormal calcitonin levels. Of the 6 patients with thyroid C-cell hyperplasia, 5 had elevated calcitonin concentrations at baseline and throughout the trial. One patient in both the liraglutide-treated group and the comparator group developed elevated calcitonin concentrations while on treatment.

Chronic Weight Management:

Uncommon (0.1% to 1%): Benign colorectal neoplasms, papillary thyroid cancer, breast cancer, malignant colorectal carcinoma

Type 2 Diabetes Mellitus:

Uncommon (0.1% to 1%): Thyroid neoplasms

Frequency not reported: Thyroid C-cell hyperplasia

Postmarketing reports: Medullary Thyroid Cancer

1. Cerner Multum, Inc. “UK Summary of Product Characteristics.” O 0

2. “Product Information. Victoza (liraglutide).” Novo Nordisk Pharmaceuticals Inc, Princeton, NJ.

3. “Product Information. Saxenda (liraglutide).” Novo Nordisk Pharmaceuticals Inc, Princeton, NJ.

4. Cerner Multum, Inc. “Australian Product Information.” O 0

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.

Related questions

  • What is the difference between Soliqua and Xultophy?

Medical Disclaimer

More about Victoza (liraglutide)

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Consumer resources

  • Victoza
  • Victoza (Advanced Reading)

Other brands: Saxenda

Professional resources

  • Victoza (AHFS Monograph)
  • … +1 more

Related treatment guides

  • Weight Loss
  • Cardiovascular Risk Reduction
  • Diabetes, Type 2

Understanding Saxenda® Side Effects

Saxenda® may cause serious side effects, including:

  • possible thyroid tumors, including cancer
  • inflammation of the pancreas (pancreatitis). Stop using Saxenda® and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back
  • gallbladder problems. Saxenda® may cause gallbladder problems, including gallstones. Some gallbladder problems need surgery. Call your health care provider if you have any of the following symptoms: pain in your upper stomach (abdomen), fever, yellowing of your skin or eyes (jaundice), and clay-colored stools
  • low blood sugar (hypoglycemia) in people with type 2 diabetes who also take medicines to treat type 2 diabetes. Saxenda® can cause low blood sugar in people with type 2 diabetes who also take medicines used to treat type 2 diabetes (such as sulfonylureas). In some people, the blood sugar may get so low that they need another person to help them. If you take a sulfonylurea medicine, the dose may need to be lowered while you use Saxenda®. Signs and symptoms of low blood sugar may include: shakiness, sweating, headache, drowsiness, weakness, dizziness, confusion, irritability, hunger, fast heartbeat, and feeling jittery. You should check your blood sugar before you start taking Saxenda® and while you take Saxenda®
  • increased heart rate. Saxenda® can increase your heart rate while you are at rest. Your health care provider should check your heart rate while you take Saxenda®. Tell your health care professional if you feel your heart racing or pounding in your chest and it lasts for several minutes when taking Saxenda®
  • kidney problems (kidney failure). Saxenda® may cause nausea, vomiting, or diarrhea leading to loss of fluids (dehydration). Dehydration may cause kidney failure, which can lead to the need for dialysis. This can happen in people who have never had kidney problems before. Drinking plenty of fluids may reduce your chance of dehydration. Call your health care provider right away if you have nausea, vomiting, or diarrhea that does not go away, or if you cannot drink liquids by mouth
  • serious allergic reactions. Serious allergic reactions can happen with Saxenda®. Stop using Saxenda® and get medical help right away if you have any symptoms of a serious allergic reaction
  • depression or thoughts of suicide. You should pay attention to any mental changes, especially sudden changes, in your mood, behaviors, thoughts, or feelings. Call your health care provider right away if you have any mental changes that are new, worse, or worry you

Common side effects of Saxenda® include nausea, diarrhea, constipation, headache, vomiting, low blood sugar (hypoglycemia), decreased appetite, upset stomach, tiredness, dizziness, stomach pain, and changes in enzyme (lipase) levels in your blood. Nausea is most common when first starting Saxenda®, but decreases over time in most people as their body gets used to the medicine. Tell your health care professional if you have any side effect that bothers you or that does not go away.

Please click here for Prescribing Information and Medication Guide for Saxenda®.

Saxenda® is a prescription medication.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Victoza

SIDE EFFECTS

The following serious adverse reactions are described below or elsewhere in the prescribing information:

  • Risk of Thyroid C-cell Tumors
  • Pancreatitis
  • Use with Medications Known to Cause Hypoglycemia
  • Renal Impairment
  • Hypersensitivity Reactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Common Adverse Reactions

The safety of Victoza in subjects with type 2 diabetes was evaluated in 5 glycemic control, placebocontrolled trials in adults and one trial of 52 weeks duration in pediatric patients 10 years of age and older . The data in Table 1 reflect exposure of 1673 adult patients to VICTOZA and a mean duration of exposure to VICTOZA of 37.3 weeks. The mean age of adult patients was 58 years, 4% were 75 years or older and 54% were male. The population was 79% White, 6% Black or African American, 13% Asian; 4% were of Hispanic or Latino ethnicity. At baseline the population had diabetes for an average of 9.1 years and a mean HbA1c of 8.4%. Baseline estimated renal function was normal or mildly impaired in 88.1% and moderately impaired in 11.9% of the pooled population.

Table 1 shows common adverse reactions in adults, excluding hypoglycemia, associated with the use of VICTOZA. These adverse reactions occurred more commonly on VICTOZA than on placebo and occurred in at least 5% of patients treated with VICTOZA. Overall, the type, and severity of adverse reactions in adolescents and children aged 10 years and above were comparable to that observed in the adult population.

Table 1 : Adverse reactions reported in ≥ 5% of VICTOZA-treated patients

Adverse Reaction Placebo
N=661 (%)
Liraglutide 1.2 mg
N= 645 (%)
Liraglutide 1.8 mg
N= 1024 (%)
Nausea 5 18 20
Diarrhea 4 10 12
Headache 7 11 10
Nasopharyngitis 8 9 10
Vomiting 2 6 9
Decreased appetite 1 10 9
Dyspepsia 1 4 7
Upper Respiratory Tract Infection 6 7 6
Constipation 1 5 5
Back Pain 3 4 5
Cumulative proportions were calculated combining studies using Cochran-Mantel-Haenszel weights.

Cumulative proportions were calculated combining studies using Cochran-Mantel-Haenszel weights.

In an analysis of placebo- and active-controlled trials, the types and frequency of common adverse reactions, excluding hypoglycemia, were similar to those listed in Table 1.

Other Adverse Reactions

Gastrointestinal Adverse Reactions

In the pool of 5 glycemic control, placebo-controlled clinical trials, withdrawals due to gastrointestinal adverse reactions, occurred in 4.3% of VICTOZA-treated patients and 0.5% of placebo-treated patients.

Withdrawal due to gastrointestinal adverse events mainly occurred during the first 2-3 months of the trials.

Injection Site Reactions

Injection site reactions (e.g., injection site rash, erythema) were reported in approximately 2% of VICTOZA-treated patients in the five double-blind, glycemic control trials of at least 26 weeks duration. Less than 0.2% of VICTOZA-treated patients discontinued due to injection site reactions.

Hypoglycemia

In 5 adult glycemic control, placebo-controlled clinical trials of at least 26 weeks duration, hypoglycemia requiring the assistance of another person for treatment occurred in 8 VICTOZA-treated patients (7.5 events per 1000 patient-years). Of these 8 VICTOZA-treated patients, 7 patients were concomitantly using a sulfonylurea.

Table 2 : Adult Incidence (%) and Rate (episodes/patient year) of Hypoglycemia in 26-Week Combination Therapy Placebo- controlled Trials

In a 26-week pediatric placebo-controlled clinical trial with a 26-week open-label extension, 21.2% of VICTOZA treated patients (mean age 14.6 years) with type 2 diabetes, had hypoglycemia with a blood glucose <54 mg/dL with or without symptoms (335 events per 1000 patient years). No severe hypoglycemic episodes occurred in the VICTOZA treatment group (severe hypoglycemia was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions).

Papillary Thyroid Carcinoma

In glycemic control trials of VICTOZA, there were 7 reported cases of papillary thyroid carcinoma in patients treated with VICTOZA and 1 case in a comparator-treated patient (1.5 vs. 0.5 cases per 1000 patient-years). Most of these papillary thyroid carcinomas were <1 cm in greatest diameter and were diagnosed in surgical pathology specimens after thyroidectomy prompted by findings on protocolspecified screening with serum calcitonin or thyroid ultrasound.

Cholelithiasis And Cholecystitis

In glycemic control trials of VICTOZA, the incidence of cholelithiasis was 0.3% in both VICTOZAtreated and placebo-treated patients. The incidence of cholecystitis was 0.2% in both VICTOZA-treated and placebo-treated patients.

In the LEADER trial , the incidence of cholelithiasis was 1.5% (3.9 cases per 1000 patient years of observation) in VICTOZA-treated and 1.1% (2.8 cases per 1000 patient years of observation) in placebo-treated patients, both on a background of standard of care. The incidence of acute cholecystitis was 1.1% (2.9 cases per 1000 patient years of observation) in VICTOZA-treated and 0.7% (1.9 cases per 1000 patient years of observation) in placebo-treated patients.

Laboratory Tests

Bilirubin

In the five glycemic control trials of at least 26 weeks duration, mildly elevated serum bilirubin concentrations (elevations to no more than twice the upper limit of the reference range) occurred in 4.0% of VICTOZA-treated patients, 2.1% of placebo-treated patients and 3.5% of active-comparator-treated patients. This finding was not accompanied by abnormalities in other liver tests. The significance of this isolated finding is unknown.

Calcitonin

Calcitonin, a biological marker of MTC, was measured throughout the clinical development program. At the end of the glycemic control trials, adjusted mean serum calcitonin concentrations were higher in VICTOZA-treated patients compared to placebo-treated patients but not compared to patients receiving active comparator. Between group differences in adjusted mean serum calcitonin values were approximately 0.1 ng/L or less. Among patients with pretreatment calcitonin <20 ng/L, calcitonin elevations to >20 ng/L occurred in 0.7% of VICTOZA-treated patients, 0.3% of placebo-treated patients, and 0.5% of active-comparator-treated patients. The clinical significance of these findings is unknown.

Lipase And Amylase

In one glycemic control trial in renal impairment patients, a mean increase of 33% for lipase and 15% for amylase from baseline was observed for VICTOZA-treated patients while placebo-treated patients had a mean decrease in lipase of 3% and a mean increase in amylase of 1%.

In the LEADER trial, serum lipase and amylase were routinely measured. Among VICTOZA-treated patients, 7.9% had a lipase value at any time during treatment of greater than or equal to 3 times the upper limit of normal compared with 4.5% of placebo-treated patients, and 1% of VICTOZA-treated patients had an amylase value at any time during treatment of greater than or equal to 3 times the upper limit of normal versus 0.7% of placebo-treated patients.

The clinical significance of elevations in lipase or amylase with VICTOZA is unknown in the absence of other signs and symptoms of pancreatitis .

Vital Signs

VICTOZA did not have adverse effects on blood pressure. Mean increases from baseline in heart rate of 2 to 3 beats per minute have been observed with VICTOZA compared to placebo.

Immunogenicity

Consistent with the potentially immunogenic properties of protein and peptide pharmaceuticals, patients treated with VICTOZA may develop anti-liraglutide antibodies. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, the incidence of antibodies to liraglutide cannot be directly compared with the incidence of antibodies of other products.

Approximately 50-70% of VICTOZA-treated patients in five double-blind clinical trials of 26 weeks duration or longer were tested for the presence of anti-liraglutide antibodies at the end of treatment. Low titers (concentrations not requiring dilution of serum) of anti-liraglutide antibodies were detected in 8.6% of these VICTOZA-treated patients. Cross-reacting anti-liraglutide antibodies to native glucagon-like peptide-1 (GLP-1) occurred in 6.9% of the VICTOZA-treated patients in the double-blind 52-week monotherapy trial and in 4.8% of the VICTOZA-treated patients in the double-blind 26-week add-on combination therapy trials. These cross-reacting antibodies were not tested for neutralizing effect against native GLP-1, and thus the potential for clinically significant neutralization of native GLP-1 was not assessed. Antibodies that had a neutralizing effect on liraglutide in an in vitro assay occurred in 2.3% of the VICTOZA-treated patients in the double-blind 52-week monotherapy trial and in 1.0% of the VICTOZA-treated patients in the double-blind 26-week add-on combination therapy trials.

Antibody formation was not associated with reduced efficacy of VICTOZA when comparing mean HbA1c of all antibody-positive and all antibody-negative patients. However, the 3 patients with the highest titers of anti-liraglutide antibodies had no reduction in HbA1c with VICTOZA treatment.

In five double-blind glycemic control trials of VICTOZA, events from a composite of adverse events potentially related to immunogenicity (e.g. urticaria, angioedema) occurred among 0.8% of VICTOZA-treated patients and among 0.4% of comparator-treated patients. Urticaria accounted for approximately one-half of the events in this composite for VICTOZA-treated patients. Patients who developed antiliraglutide antibodies were not more likely to develop events from the immunogenicity events composite than were patients who did not develop anti-liraglutide antibodies.

In the LEADER trial , anti-liraglutide antibodies were detected in 11 out of the 1247 (0.9%) VICTOZA-treated patients with antibody measurements.

Of the 11 VICTOZA-treated patients who developed anti-liraglutide antibodies, none were observed to develop neutralizing antibodies to liraglutide, and 5 patients (0.4%) developed cross-reacting antibodies against native GLP-1.

In a clinical trial with pediatric patients 10 to 17 years , anti-liraglutide antibodies were detected in 1 (1.5%) VICTOZA treated patient at week 26 and 5 (8.5%) VICTOZA treated patients at week 53. None of the 5 had antibodies cross reactive to native GLP-1 or had neutralizing antibodies.

Post-Marketing Experience

The following additional adverse reactions have been reported during post-approval use of VICTOZA. Because these events are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  • Medullary thyroid carcinoma
  • Dehydration resulting from nausea, vomiting and diarrhea.
  • Increased serum creatinine, acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis.
  • Angioedema and anaphylactic reactions.
  • Allergic reactions: rash and pruritus
  • Acute pancreatitis, hemorrhagic and necrotizing pancreatitis sometimes resulting in death
  • Hepatobiliary disorders: elevations of liver enzymes, hepatitis

Read the entire FDA prescribing information for Victoza (Liraglutide Injection)

Victoza (liraglutide)

Victoza can cause mild or serious side effects. The following lists contain some of the key side effects that may occur while taking Victoza. These lists do not include all possible side effects.

For more information on the possible side effects of Victoza, talk with your doctor or pharmacist. They can give you tips on how to deal with any side effects that may be bothersome.

Note: The Food and Drug Administration (FDA) tracks side effects of drugs they’ve approved. If you would like to report to the FDA a side effect you’ve had with Victoza, you can do so through MedWatch.

More common side effects

The more common side effects of Victoza can include:

  • headache
  • nausea
  • vomiting
  • diarrhea
  • constipation
  • indigestion
  • loss of appetite
  • hypoglycemia (low blood sugar), which is more common in children than in adults

Most of these side effects may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk with your doctor or pharmacist.

Serious side effects

Serious side effects from Victoza aren’t common, but they can occur. Call your doctor right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency.

Serious side effects and their symptoms can include the following:

  • Gallbladder disease. Symptoms can include:
    • pain in your belly
    • nausea
    • vomiting
    • fever
    • diarrhea
    • jaundice (yellowing of your skin and the whites of your eyes)
  • Kidney problems, which may be caused by dehydration. Symptoms can include:
    • urinating less often than usual
    • swelling in your feet and lower legs
    • drowsiness
    • confusion
    • shortness of breath
    • nausea

Other serious side effects, which are discussed in detail below, include:

  • pancreatitis (inflammation in your pancreas)
  • severe allergic reaction
  • possible risk of thyroid cancer*

* Victoza has aboxed warningfrom the FDA regarding the possible risk of thyroid cancer in humans. A boxed warning is the strongest warning the FDA requires. It alerts doctors and patients about drug effects that may be dangerous.

Side effect details

You may wonder how often certain side effects occur with this drugor whether certain side effects pertain to it. Here’s some detail on several of the side effects this drug may or may not cause.

Allergic reaction

As with most drugs, some people can have an allergic reaction after taking Victoza. It’s not known how many people taking Victoza have had an allergic reaction to the drug. Symptoms of a mild allergic reaction can include:

  • skin rash
  • itchiness
  • flushing (warmth and redness in your skin)

A more severe allergic reaction is rare but possible. Symptoms of a severe allergic reaction can include:

  • swelling under your skin, typically in your eyelids, lips, hands, or feet
  • swelling of your tongue, mouth, or throat
  • trouble breathing or speaking

Call your doctor right away if you have a severe allergic reaction to Victoza. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency.

Pancreatitis

Pancreatitis (inflammation in your pancreas) is a possible side effect of Victoza. This condition occurred in people taking the drug during clinical studies.

In clinical studies, 2.7 cases of pancreatitis occurred out of every 1,000 people taking Victoza for 1 year. Out of every 1,000 people taking glimepiride (a different diabetes drug that’s taken by mouth) for 1 year, 0.5 cases of pancreatitis occurred.

There have also been cases of pancreatitis in post-marketing reports of Victoza. These cases of the condition were reported after Victoza was made available to the public.

However, it’s not usually possible to determine if a drug caused the condition seen in post-marketing reports. It’s also not possible to know how common the condition is in people taking the drug.

When you take Victoza, your doctor will monitor you for symptoms of pancreatitis. These symptoms may include:

  • severe pain that wraps around your upper belly (stomach pain) and your back
  • upset stomach
  • nausea
  • vomiting
  • bloating
  • fever

It’s not known if you’ll have a higher risk of pancreatitis while you’re taking Victoza if you’ve had pancreatitis in the past.

If you have any symptoms of pancreatitis while taking Victoza, tell your doctor right away. They will likely stop Victoza treatment to help treat your pancreatitis. It’s recommended that you don’t restart Victoza treatment after you’ve had pancreatitis.

Nausea

You may have nausea while you’re taking Victoza. It’s one of the most common side effects of the drug. In clinical studies, 18% to 20% of people who took Victoza had nausea. Of those who took a placebo (treatment with no active drug), 5% had nausea.

Nausea can also be a symptom of more serious side effects of Victoza, such as pancreatitis or gallbladder disease.

If you have nausea while you’re taking Victoza, tell your doctor. They will recommend ways to reduce this side effect. They’ll also determine whether your nausea is related to more serious side effects.

Diarrhea

Some people have diarrhea while taking Victoza. This is a common side effect of the drug. In clinical studies, 10% to 12% of people who took Victoza had diarrhea. Of people who took a placebo (treatment with no active drug), 4% had diarrhea.

If you have diarrhea while you’re taking Victoza, tell your doctor. They will recommend ways to reduce this side effect. They will also recommend ways to prevent dehydration (low fluid level), which can lead to more serious problems, such as kidney damage.

Constipation

It’s possible to feel constipated while you’re using Victoza. In clinical studies, 5% of people who took Victoza had constipation. Of people who took a placebo (treatment with no active drug), 1% had constipation.

If you have constipation while you’re taking Victoza, tell your doctor. They will recommend ways to help you keep your bowel movements regular in timing.

Cancer

Cancer was not reported as a side effect of Victoza in clinical studies. However, animal studies of the drug found an increased risk of thyroid cancer. (See the section below called “Thyroid cancer” for more details.)A clinical study that included more than 9,000 people looked at the risk of neoplasms (abnormal growths, including cancer) in people taking Victoza. People with type 2 diabetes who had risk of cardiovascular problems were studied.

In this study, people took either Victoza or a placebo (treatment with no active drug) for 3.5 to 5 years. The researchers didn’t find an increased risk of cancer in people taking Victoza compared to people taking the placebo. However, more studies are needed to confirm these results.

If you’ve ever had cancer or you have a family history of cancer, talk with your doctor. They can discuss whether Victoza is safe for you.

Thyroid cancer

In animal studies, Victoza was found to cause thyroid tumors (abnormal growths) and thyroid cancer. It’s not known if Victoza causes thyroid tumors or thyroid cancer in humans.

Because of this potential risk, Victoza has a boxed warning for increased risk of thyroid tumors. A boxed warning is the most serious warning from the Food and Drug Administration (FDA). It alerts doctors and patients about drug effects that may be dangerous.

However, in clinical studies, the rate of papillary thyroid cancer (the most common type of thyroid cancer) was 1.5 cases for every 1,000 people taking Victoza for a year. Of those taking either a placebo (treatment with no active drug) or a different diabetes drug, the rate was 0.5 cases for every 1,000 people taking the drug or placebo for a year.

There have also been cases of medullary thyroid cancer (MTC) in post-marketing reports. (This means these cases were reported after Victoza was made available to the public.)

However, it’s typically not possible to determine whether a drug caused the condition seen in post-marketing reports. It’s also not possible to know how common this type of cancer is in people using the drug.

Because of these reports, you shouldn’t take Victoza if you or any of your family members have had MTC. You also shouldn’t take Victoza if you have a condition called multiple endocrine neoplasia syndrome type 2 (MEN 2). This syndrome is a hormone-related condition that may increase your risk of thyroid cancer if you take Victoza.

Tell your doctor if you have any unusual symptoms that may be related to thyroid tumors or thyroid cancer. Symptoms of these conditions may include:

  • a lump or swollen area in your throat
  • hoarseness in your voice
  • trouble swallowing
  • shortness of breath

If you’d like to know more about the possible risk of thyroid cancer while using Victoza, talk with your doctor.

Headache

You may have headaches while you’re taking Victoza. This is one of the most common side effects of the drug. In clinical studies, 10% to 11% of people who took Victoza had headaches. Of people who took a placebo (treatment with no active drug), 7% had headaches.

If you have headaches while you’re taking Victoza, talk with your doctor. They can recommend ways to help reduce this side effect.

Hypoglycemia

Hypoglycemia (low blood sugar) is a possible side effect of Victoza. In clinical studies, there were 7.5 cases of severe hypoglycemia for every 1,000 people taking Victoza for 1 year. The hypoglycemia that occurred required help from another person to treat.

Of the people affected, 87.5% of them were taking Victoza in combination with a sulfonylurea (a class of diabetes drugs that are taken by mouth). Examples of sulfonylurea drugs include glimepiride (Amaryl) and glipizide (Glucotrol).

People who took Victoza also had hypoglycemia events that they were able to treat themselves. In clinical studies, the number of hypoglycemia events for each person who took the following drugs for 1 year were:

  • 3.6 events in people taking Victoza and metformin (compared to 2.5 events in those taking a placebo and metformin)
  • 7.5 events in people taking Victoza and glimepiride (compared to 2.6 events in those taking a placebo and glimepiride)
  • 7.9 events in people taking Victoza, metformin, and rosiglitazone (compared to 4.6 events in those taking a placebo, metformin, and rosiglitazone)
  • 27.4 events in people taking Victoza, metformin, and glimepiride (compared to 16.7 events in those taking a placebo, metformin, and glimepiride)

Note: A placebo is a treatment that doesn’t contain any active drug.

Symptoms of hypoglycemia can include:

  • shakiness
  • dizziness
  • confusion
  • sweating
  • anxiety
  • fast heart rate
  • headache

If you have symptoms of hypoglycemia, check your blood sugar level right away. If you don’t have a blood glucose (sugar) meter and aren’t able to check your level, you should treat yourself for hypoglycemia anyway.

Treating hypoglycemia

You can treat mild or moderate hypoglycemia by eating or drinking things that have at least 15 grams of glucose in them. Examples of these items include:

  • half a cup of fruit juice, such as orange juice
  • half a cup of non-diet soda
  • 3 or 4 glucose tablets (you can purchase these from your pharmacy)
  • 1 tablespoon of sugar or honey

After you’ve had something to eat or drink, check your blood sugar level again in 15 minutes. If the level is still low, you may need to consume more glucose.

If your hypoglycemia is more severe and you need assistance, tell people who are around that you need help or call 911. Don’t try to drive yourself to the emergency room.

Liver side effects

It’s possible to have liver side effects while you’re taking Victoza. Post-marketing reports showed that some people who took Victoza have had hepatitis (inflammation in their liver). Post-marketing reports show cases of side effects that happened after the drug was made available to the public.

There have also been post-marketing reports of people taking Victoza who had high levels of liver enzymes (certain proteins made in your liver). High levels of liver enzymes are often a sign of liver damage.

However, it’s typically not possible to determine whether a drug caused a side effect seen in post-marketing reports. It’s also not possible to know how common a side effect may be in people taking the drug.

Symptoms of liver problems include:

  • nausea
  • diarrhea
  • loss of appetite
  • fatigue (lack of energy)
  • jaundice (yellowing of your skin and the whites of your eyes)
  • fluid buildup in your belly and legs

If you have symptoms of liver problems while taking Victoza, tell your doctor. They can order tests and recommend medical treatment if needed.

Skin rash

You may have skin rashes while you’re using Victoza.

In clinical studies, about 2% of people who took Victoza had a rash near the area of their Victoza injection site (called an injection site reaction). However, less than 0.2% of people who took Victoza stopped treatment because of injection site reactions.

Skin rash may also be a symptom of an allergic reaction to Victoza. See the “Allergic reaction” section above for more information.

If you have a rash while you’re taking Victoza, tell your doctor right away. If you have a rash along with other symptoms, such as trouble breathing or swelling of your tongue, lips, or throat, call 911 and get medical help right away. These could be signs of a severe allergic reaction.

Gastroparesis (not a side effect)

Gastroparesis was not reported as a side effect of Victoza during clinical studies. With this condition, your stomach empties very slowly as it moves food through your digestive tract.

Although it hasn’t been shown to cause gastroparesis, Victoza can worsen the condition in people who already have it. Victoza works to improve your blood sugar levels by slowing the action of your stomach muscles. This causes food to move more slowly through your gastrointestinal system than it usually does. So if you already have gastroparesis, Victoza could worsen your condition.

If you have gastroparesis or problems digesting food, talk with your doctor. They’ll advise whether it’s safe for you to take Victoza.

Side effects in children

During clinical studies, side effects of Victoza were similar in both children and adults. However, children had higher rates of hypoglycemia (low blood sugar) than adults did.

In a 26-week clinical study, children with type 2 diabetes took Victoza and metformin. Some of the children also took a long-acting insulin.

In this study, 21.2% of the children had hypoglycemia episodes. This rate can be described as 335 hypoglycemia events for every 1,000 children who took Victoza for 1 year. None of the hypoglycemia episodes were considered severe enough to need another person to help treat the children.

However, if you care for a child who takes Victoza, be prepared to recognize the symptoms of hypoglycemia and treat the condition. (See the “Hypoglycemia” section above.) Treating hypoglycemia right away can help prevent a medical emergency.

Q1. What is FDA announcing today?

A. FDA is approving Victoza (liraglutide), a once-daily injection to treat type 2 diabetes mellitus (T2DM) in adults. Victoza is intended to help lower blood sugar (glucose) levels, along with diet and exercise. Controlling elevated blood sugar levels is important in preventing complications of diabetes, such as kidney disease and blindness.

People with T2DM have difficulty making and using insulin, a hormone that helps prevent glucose from building up in the blood. Victoza works by helping the pancreas release more insulin after eating a meal.

Although there are many anti-diabetic medications already available for use, often people with T2DM will require different or additional anti-diabetic medications to control their blood sugar, given the chronic nature of this disease.Therefore, Victoza is another medication that can be used to help control blood sugar, but it is not recommended as first-line therapy for patients whose blood sugar is not controlled through diet and exercise.

Q2. Should healthcare professionals be aware of any safety issues associated with Victoza?

A. FDA approved Victoza because the Agency believes that the benefits of this drug to patients with T2DM outweigh potential risks associated with its use. There were, however, several safety concerns identified during the Victoza review that had to be evaluated in light of its benefits. These safety concerns included:

  • Clinical trials that suggested Victoza may be associated with pancreatitis (see Q3). Other drugs that work through similar mechanisms as Victoza have also been associated with pancreatitis.
  • Animal data that showed a rare type of thyroid cancer known as medullary thyroid cancer associated with liraglutide, although the relevance of this finding to humans remains unknown (see Q5).

To ensure that the benefits of Victoza continue to outweigh any risks, FDA has required a Risk Evaluation and Mitigation Strategy (REMS) as part of the Victoza approval. This REMS includes a patient Medication Guide and a Communication Plan. FDA has also required additional studies to better understand the risks associated with this medicine. In addition, FDA has required a large cardiovascular safety trial, that is now required as part of the development of most diabetic medications (See Q7).

Q3. What information did FDA review about pancreatitis associated with the use of Victoza?

A. The Victoza trials were carefully reviewed for cases of pancreatitis, a side effect associated with other diabetic medications that work in a similar manner to this medicine. In five clinical trials including more than 3,900 people, there were seven cases of pancreatitis in patients using Victoza and one case in a patient using another diabetes medicine. This constituted a 4:1 imbalance of pancreatitis cases, when considering the number of patient exposures. Although there were too few cases to know if Victoza causes pancreatitis, healthcare professionals and patients should be aware of this potential risk, and know that some common side effects of Victoza may be similar to the symptoms of pancreatitis (see Q4).

Q4. What steps does FDA recommend patients and healthcare professionals take to reduce the risk of developing pancreatitis while using Victoza?

A. Patients taking Victoza should be aware of the symptoms of pancreatitis, such as severe abdominal pain that may also radiate into the back, possibly with nausea, and vomiting. If patients experience these symptoms, they should immediately talk to their healthcare professional.

As part of the REMS, patients will be given a Medication Guide to provide them with information about pancreatitis, including:

  • What conditions, in general, may place them at higher risk for pancreatitis; for example, prior history of pancreatitis, gallstones, excessive use of alcohol, or very high blood triglyceride levels.
  • The symptoms of pancreatitis (described above) and what they need to do if they occur.

If healthcare professionals suspect a patient has pancreatitis, Victoza should be stopped right away and the patient should undergo testing to confirm pancreatitis. If pancreatitis is confirmed, Victoza should not be restarted. Victoza has not been studied in enough patients who have had pancreatitis in the past to know if they are at higher risk for developing pancreatitis while using the medicine. For this reason, Victoza should always be used with caution in patients with a history of pancreatitis.

As part of the REMS, the Communication Plan for healthcare professionals highlights how to appropriately select patients for treatment with Victoza. It also reminds healthcare professionals to promptly evaluate patients who develop symptoms suggestive of pancreatitis.

Q5. What information did FDA review about medullary thyroid cancer and Victoza?

A. Studies were done in mice and in rats to look for any evidence that liraglutide might cause cancer in animals. Results of the studies showed that liraglutide caused malignant tumors of the thyroid gland, especially at doses that were 8-times higher than what humans would receive. It is hard to predict whether this finding means that humans who take liraglutide might be at risk for developing medullary thyroid cancer. This specific type of thyroid cancer is very rare in humans (about 600 cases per year in the United States) so even if liraglutide increased the risk for a patient to develop it, cases still might not be detected during the clinical trials.

As a result of the animal study results, the clinical development program for Victoza included blood tests for a biomarker for medullary thyroid cancer—a blood calcitonin test. Data from a two-year study did not show any difference in calcitonin levels between patients treated with Victoza compared to other diabetes medicines. With these data, FDA is of the opinion that this safety concern was adequately addressed during Victoza’s development.

However, as part of FDA’s commitment to post-marketing safety evaluation, the Agency is requiring the manufacturer of Victoza to conduct a 5-year epidemiological study using a large healthcare claims database to compare the development of thyroid cancer among patients with T2DM who use Victoza to those who are not using this medicine. In addition, FDA is requiring the manufacturer to develop a medullary thyroid cancer registry to monitor how many cases of medullary thyroid cancer occur each year for at least 15 years to see whether there is any association of this specific type of thyroid cancer with Victoza therapy.

Q6. What steps is FDA taking to inform patients and healthcare professionals about the potential risk of medullary thyroid cancer with the use of Victoza?

A. Patients using Victoza will receive a Medication Guide with every prescription that explains the potential risk of medullary thyroid cancer, who should not take the medication, and what symptoms to be aware of that may require additional evaluation by a healthcare professional.

A communication plan has been developed to ensure that healthcare professionals recognize the potential risk of medullary thyroid cancer in patients using Victoza. This communication plan will include:

  • A Dear Healthcare Provider letter that will be sent to all healthcare professionals likely to prescribe Victoza.
  • Representatives of Novo Nordisk (the maker of Victoza) will distribute Highlighted Information for Prescribers at their first meeting with prescribers.
  • A link on the Victoza website that will take healthcare professionals and patients to all of these documents.

FDA is also requiring the manufacturer of Victoza to conduct additional animal studies in mice to further evaluate the potential risk of medullary thyroid cancer in humans.

Q7. Are there any other studies FDA is requiring for Victoza?

A. In December 2008, FDA issued a Guidance for Industry that required manufacturers of new treatments for diabetes to carefully design and evaluate their clinical trials for cardiovascular safety. The Victoza application for approval was submitted before the December 2008 guidance was issued; therefore, the manufacturer had not designed the recommended cardiovascular safety trials. FDA, however, reviewed the available cardiovascular safety data, and determined there was no evidence of excess cardiovascular risk associated with Victoza. The April 2009 FDA Endocrinologic and Metabolic Drugs Advisory Committee met, discussed, and a majority of the members voted that the available data adequately addressed the cardiovascular safety concern to support approval.

Still, FDA is requiring a post-approval study that specifically evaluates cardiovascular safety in a higher risk population as part of the Agency’s commitment to post-marketing safety evaluation.

Related Information

  • Liraglutide (marketed as Victoza) Information
  • FDA Approves New Treatment for Type 2 Diabetes

Learn how to care for your Victoza® pen

Follow these instructions on how to care for your Victoza® pen. Remember that your doctor or diabetes care team should teach you how to use the pen. You should also read the Instructions for Use and Medication Guide, which provide full information.

If you have questions about using, caring for, or storing your Victoza® pen, call 1-877-905-1126 to speak with a VictozaCare™ Coach. They’re available Monday through Friday, 8:30 am to 6:00 pm ET.

Caring for the Victoza® pen

  • After removing the needle and discarding it properly, put the cap on your Victoza® pen and store your Victoza® pen without the needle attacheda
  • Do not try to refill your Victoza® pen—it is prefilled and is disposable
  • Do not try to repair your pen or pull it apart
  • Keep your Victoza® pen away from dust, dirt, and liquids
  • If cleaning is needed, wipe the outside of the pen with a clean, damp cloth

Victoza® storage

Before use

  • Store your new, unused Victoza® pen in the refrigerator at 36°F to 46°F (2°C to 8°C)
  • If Victoza® is stored outside of the refrigerator (by mistake) prior to first use, it should be used or thrown away within 30 days
  • Do not freeze Victoza® or use Victoza® if it has been frozen. Do not store Victoza® near the refrigerator cooling element

Victoza® pen in use

  • Store your Victoza® pen for 30 days at 59°F to 86°F (15°C to 30°C), or in a refrigerator at 36°F to 46°F (2°C to 8°C)
  • When carrying the Victoza® pen away from home, store the pen at a temperature between 59°F and 86°F (15°C and 30°C)
  • If Victoza® has been exposed to temperatures above 86°F (30°C), it should be thrown away
  • Protect your Victoza® pen from excessive heat and sunlight
  • Keep the cap on when your Victoza® pen is not in use
  • Use a Victoza® pen for only 30 days. Throw away a used Victoza® pen after 30 days

Important information

  • Do not share your Victoza® pen with another person, even if the needle is changed. You may give another person an infection or get an infection from them
  • Keep your Victoza® pen out of the reach of children
  • Always use a new needle for each injectiona
  • If you drop your Victoza® pen, repeat “First-Time Use for Each New Pen” (steps A through D in the Instructions for Use)
  • Be careful not to bend or damage the needle
  • Do not use the cartridge scale to measure how much Victoza® to inject
  • Remove the needle from the Victoza® pen after each injection. This helps to ensure sterility and prevent leakage of Victoza®, and will help to make sure you inject the right dose of Victoza® for future injections
  • Be careful when handling used needles to avoid needle sticks
  • You can use your Victoza® pen for up to 30 days after you use it for the first time

Victoza® pen safety

Do not store the Victoza® pen with the needle attached.a Always safely remove and safely discard the needle after each injection. This may help prevent contamination, infection, and leakage. It also helps to make sure that you get the correct dose of Victoza®.

Do not share your Victoza® pen with another person, even if the needle is changed. You may give another person an infection or get an infection from them.

Keep your Victoza® pen, pen needles, and all medications out of the reach of children.

For more information about how to dispose of used pen needles and used Victoza® pens, see the Instructions for Use.

aPen needles are sold separately and may require a prescription in some states.

Victoza in Clinical Practice

Endocrinologist Suneil Koliwad, MD, PhD, says that plenty of drugs effectively treat type 2 diabetes, and he sees no reason to “aggressively defend” the use of Victoza. Compared to drugs that have long and proven safety records, he says, Victoza’s safety is not thoroughly established, and he is particularly concerned about inflammation of the pancreas.

“The drug’s trial was not long enough to see a sufficient safety record,” says Koliwad, an assistant professor of medicine at the University of California San Francisco’s Diabetes Center. “How rare is rare enough that we accept safety risks and still give this to our patients? Some medications we do give because they are the best available. Here that is not the case.”

Koliwad says that some patients may benefit from Victoza and drugs in its class, but they should be thoroughly counseled prior to taking it. And he says that doctors should look at all of the available drugs before prescribing Victoza and similar medications. For those patients taking it already, Koliwad says they should stay on it if it works and is not causing problems.

“The primary concern should be that you are controlling your diabetes,” says Koliwad.

Spyros Mezitis, MD, PhD, agrees.

“If there are no issues, we continue patients on the drug and we continue monitoring them while on it,” says Mezitis, an endocrinologist at Lenox Hill Hospital in New York City who prescribes Victoza to patients only after a comprehensive discussion of their family health history, particularly regarding their thyroid.

Visit your doctor or health care professional for regular checks on your progress.

Drink plenty of fluids while taking this medicine. Check with your doctor or health care professional if you get an attack of severe diarrhea, nausea, and vomiting. The loss of too much body fluid can make it dangerous for you to take this medicine.

A test called the HbA1C (A1C) will be monitored. This is a simple blood test. It measures your blood sugar control over the last 2 to 3 months. You will receive this test every 3 to 6 months.

Learn how to check your blood sugar. Learn the symptoms of low and high blood sugar and how to manage them.

Always carry a quick-source of sugar with you in case you have symptoms of low blood sugar. Examples include hard sugar candy or glucose tablets. Make sure others know that you can choke if you eat or drink when you develop serious symptoms of low blood sugar, such as seizures or unconsciousness. They must get medical help at once.

Tell your doctor or health care professional if you have high blood sugar. You might need to change the dose of your medicine. If you are sick or exercising more than usual, you might need to change the dose of your medicine.

Do not skip meals. Ask your doctor or health care professional if you should avoid alcohol. Many nonprescription cough and cold products contain sugar or alcohol. These can affect blood sugar.

Pens should never be shared. Even if the needle is changed, sharing may result in passing of viruses like hepatitis or HIV.

Wear a medical ID bracelet or chain, and carry a card that describes your disease and details of your medicine and dosage times.

Victoza 6 mg/ml solution for injection in pre-filled pen

Pharmacotherapeutic group: Drugs used in diabetes, glucagon-like peptide-1 (GLP-1) analogues. ATC code: A10BJ02

Mechanism of action

Liraglutide is a GLP-1 analogue with 97% sequence homology to human GLP-1 that binds to and activates the GLP-1 receptor. The GLP-1 receptor is the target for native GLP-1, an endogenous incretin hormone that potentiates glucose-dependent insulin secretion from the pancreatic beta cells. Unlike native GLP-1, liraglutide has a pharmacokinetic and pharmacodynamic profile in humans suitable for once daily administration. Following subcutaneous administration, the protracted action profile is based on three mechanisms: self-association, which results in slow absorption; binding to albumin; and higher enzymatic stability towards the dipeptidyl peptidase -4 (DPP-4) and neutral endopeptidase (NEP) enzymes, resulting in a long plasma half-life.

Liraglutide action is mediated via a specific interaction with GLP-1 receptors, leading to an increase in cyclic adenosine monophosphate (cAMP). Liraglutide stimulates insulin secretion in a glucose-dependent manner. Simultaneously, liraglutide lowers inappropriately high glucagon secretion, also in a glucose-dependent manner. Thus, when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. Conversely, during hypoglycaemia liraglutide diminishes insulin secretion and does not impair glucagon secretion. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying. Liraglutide reduces body weight and body fat mass through mechanisms involving reduced hunger and lowered energy intake, GLP-1 is a physiological regulator of appetite and food intake, but the exact mechanism of action is not entirely clear.

In animal studies, peripheral administration of liraglutide led to uptake in specific brain regions involved in regulation of appetite, where liraglutide via specific activation of the GLP-1 receptor (GLP-1R) increased key satiety and decreased key hunger signals, thereby leading to lower body weight.

GLP-1 receptors are also expressed in specific locations in the heart, vasculature, immune system, and kidneys. In mouse models of atherosclerosis, liraglutide prevented aortic plaque progression and reduced inflammation in the plaque. In addition, liraglutide had a beneficial effect on plasma lipids. Liraglutide did not reduce the plaque size of already established plaques.

Pharmacodynamic effects

Liraglutide has 24-hour duration of action and improves glycaemic control by lowering fasting and postprandial blood glucose in patients with type 2 diabetes mellitus.

Clinical efficacy and safety

Both improvement of glycaemic control and reduction of cardiovascular morbidity and mortality are an integral part of the treatment of type 2 diabetes.

Five double-blind, randomised, controlled clinical phase 3a adult trials were conducted to evaluate the effects of liraglutide on glycaemic control (Table 2). Treatment with liraglutide produced clinically and statistically significant improvements in glycosylated haemoglobin A1c (HbA1c), fasting plasma glucose and postprandial glucose compared with placebo.

These trials included 3,978 exposed patients with type 2 diabetes mellitus (2,501 patients treated with liraglutide), 53.7% men and 46.3% women, 797 patients (508 treated with liraglutide) were ≥65 years of age and 113 patients (66 treated with liraglutide) were ≥75 years of age.

Additional trials were conducted with liraglutide that included 1,901 patients in four unblinded, randomised, controlled clinical trials (including 464, 658, 323 and 177 patients per trial) and one double-blind, randomised, controlled clinical trial in patients with type 2 diabetes mellitus and moderate renal impairment (279 patients).

A large cardiovascular outcomes trial (the LEADER trial) was also conducted with liraglutide in 9,340 patients with type 2 diabetes mellitus at high cardiovascular risk.

• Glycaemic control

Monotherapy

Liraglutide monotherapy for 52 weeks resulted in statistically significant and sustained reductions in HbA1c compared with glimepiride 8 mg (-0.84% for 1.2 mg, -1.14% for 1.8 mg vs -0.51% for comparator) in patients previously treated with either diet and exercise or OAD monotherapy at no more than half-maximal dose (Table 2).

Combination with oral antidiabetics

Liraglutide in combination therapy, for 26 weeks, with metformin, glimepiride or metformin and rosiglitazone or SGLT2i ± metformin resulted in statistically significant and sustained reductions in HbA1c compared with patients receiving placebo (Table 2).

Table 2 Liraglutide clinical phase 3 trials in monotherapy (52 weeks) and in combination with oral antidiabetics (26 weeks)

1all patients; 2previous OAD monotherapy; 3previous diet treated patients

5Victoza add-on to SGLT2i was investigated at all approved doses of SGLT2i

4the dosing of insulin glargine was open-labelled and was applied according to Guideline for titration of insulin glargine. Titration of the insulin glargine dose was managed by the patient after instruction by the investigator:

Guideline for titration of insulin glargine

a According to the individualised recommendation by the investigator at the previous visit, for example depending on whether the patient has experienced hypoglycaemia.

Combination with insulin

In a 104-week clinical trial, 57% of patients with type 2 diabetes treated with insulin degludec in combination with metformin achieved a target HbA1c <7% and the remaining patients continued in a 26-week open label trial and were randomised to add liraglutide or a single dose of insulin aspart (with the largest meal). In the insulin degludec + liraglutide arm, the insulin dose was reduced by 20% in order to minimize the risk of hypoglycaemia. Addition of liraglutide resulted in a statistically significantly greater reduction of HbA1c (-0.73% for liraglutide vs -0.40% for comparator) and body weight (-3.03 vs 0.72 kg). The rate of hypoglycaemic episodes (per patient year of exposure) was statistically significantly lower when adding liraglutide compared to adding a single dose of insulin aspart (1.0 vs 8.15; ratio: 0.13; 95% CI: 0.08 to 0.21).

In a 52-week clinical trial, the addition of insulin detemir to liraglutide 1.8 mg and metformin in patients not achieving glycaemic targets on liraglutide and metformin alone resulted in a HbA1c decrease from baseline of 0.54%, compared to 0.20% in the liraglutide 1.8 mg and metformin control group. Weight loss was sustained. There was a small increase in the rate of minor hypoglycaemic episodes (0.23 versus 0.03 events per patient years).

In the LEADER trial, (see subsection Cardiovascular evaluation), 873 patients were on premix insulin (with or without OAD(s)) at baseline and at least for the following 26 weeks. The mean HbA1c at baseline was 8.7% for liraglutide and placebo. At week 26, the estimated mean change in HbA1c was -1.4% and -0.5% for liraglutide and placebo, respectively, with an estimated treatment difference of -0.9 95% CI. The safety profile of liraglutide in combination with premix insulin was overall comparable to that observed for placebo in combination with premix insulin (see section 4.8).

Use in patients with renal impairment

In a double-blind trial comparing the efficacy and safety of liraglutide 1.8 mg versus placebo as add-on to insulin and/or OAD in patients with type 2 diabetes and moderate renal impairment, liraglutide was superior to placebo treatment in reducing HbA1c after 26 weeks (-1.05% vs -0.38%). Significantly more patients achieved HbA1c below 7% with liraglutide compared with placebo (52.8% vs 19.5%). In both groups a decrease in body weight was seen: -2.4 kg with liraglutide vs -1.09 kg with placebo. There was a comparable risk of hypoglycaemic episodes between the two treatment groups. The safety profile of liraglutide was generally similar to that observed in other studies with liraglutide.

• Proportion of patients achieving reductions in HbA1c

Liraglutide alone resulted in a statistically significant greater proportion of patients achieving HbA1c ≤6.5% at 52 weeks compared with patients receiving glimepiride (37.6% for 1.8 mg and 28.0% for 1.2 mg vs 16.2% for comparator).

Liraglutide in combination with metformin, glimepiride, metformin and rosiglitazone or SGLT2i ± metformin resulted in a statistically significant greater proportion of patients achieving an HbA1c ≤6.5% at 26 weeks compared with patients receiving these agents alone.

• Fasting plasma glucose

Treatment with liraglutide alone and in combination with one or two oral antidiabetic drugs resulted in a reduction in fasting plasma glucose of 13–43.5 mg/dl (0.72–2.42 mmol/l). This reduction was observed within the first two weeks of treatment.

• Postprandial glucose

Liraglutide reduced postprandial glucose across all three daily meals by 31–49 mg/dl (1.68–2.71 mmol/l).

• Beta-cell function

Clinical trials with liraglutide indicate improved beta-cell function based on measures such as the homeostasis model assessment for beta-cell function (HOMA-B) and the proinsulin to insulin ratio. Improved first and second phase insulin secretion after 52 weeks treatment with liraglutide was demonstrated in a subset of patients with type 2 diabetes (n=29).

• Body weight

Treatment with liraglutide in combination with metformin, metformin and glimepiride, metformin and rosiglitazone or SGLT2i with or without metformin was associated with a sustained weight reduction in the range from 0.86 kg to 2.62 kg compared with placebo.

Larger weight reduction was observed with increasing body mass index (BMI) at baseline.

• Cardiovascular evaluation

Post-hoc analysis of serious major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke) from all intermediate and long-term phase 2 and 3 trials (ranging from 26 and up to 100 weeks duration) including 5,607 patients (3,651 exposed to liraglutide), showed no increase in cardiovascular risk (incidence ratio of 0.75 (95% CI 0.35; 1.63)) for liraglutide versus all comparators.

The Liraglutide Effect and Action in Diabetes Evaluation of Cardiovascular Outcome Results (LEADER) trial, was a multicentre, placebo-controlled, double-blind clinical trial. 9,340 patients were randomly allocated to either liraglutide (4,668) or placebo (4,672), both in addition to standards of care for HbA1c and cardiovascular (CV) risk factors. Primary outcome or vital status at end of trial was available for 99.7% and 99.6% of participants randomised to liraglutide and placebo, respectively. The duration of observation was a minimum of 3.5 years and up to a maximum of 5 years. The study population included patients ≥65 years (n=4,329) and ≥75 years (n=836) and patients with mild (n=3,907), moderate (n=1,934) or severe (n=224) renal impairment. The mean age was 64 years and the mean BMI was 32.5 kg/m². The mean duration of diabetes was 12.8 years.

The primary endpoint was the time from randomisation to first occurrence of any major adverse cardiovascular events (MACE): CV death, non-fatal myocardial infarction or non-fatal stroke. Liraglutide was superior in preventing MACE vs placebo (Figure 1). The estimated hazard ratio was consistently below 1 for all 3 MACE components.

Liraglutide also significantly reduced the risk of expanded MACE (primary MACE, unstable angina pectoris leading to hospitalisation, coronary revascularisation, or hospitalisation due to heart failure) and other secondary endpoints (Figure 2).

Figure 1: Kaplan Meier plot of time to first MACE – FAS population

Figure 2: Forest plot of analyses of individual cardiovascular event types – FAS population

• Blood pressure and heart rate

Over the duration of the phase 3a trials, liraglutide decreased the systolic blood pressure on average of 2.3 to 6.7 mmHg from baseline and compared to active comparator the decrease was 1.9 to 4.5 mmHg.

A mean increase in heart rate from baseline of 2 to 3 beats per minute has been observed with liraglutide in long-term clinical trials including LEADER. In the LEADER trial, no long-term clinical impact of increased heart rate on the risk of cardiovascular events was observed.

• Microvascular evaluation

In the LEADER trial, microvascular events comprised nephropathy and retinopathy outcomes. The analysis of time to first microvascular event for liraglutide vs placebo had a HR of 0.84 . The HR for liraglutide vs placebo was 0.78 for time to first nephropathy event and 1.15 for time to first retinopathy event.

• Immunogenicity

Consistent with the potentially immunogenic properties of medicinal products containing proteins or peptides, patients may develop anti-liraglutide antibodies following treatment with liraglutide. On average, 8.6% of patients developed antibodies. Antibody formation has not been associated with reduced efficacy of liraglutide.

Paediatric population

In a double-blind study comparing the efficacy and safety of Victoza 1.8 mg versus placebo as add-on to metformin ± insulin in adolescents and children aged 10 years and above with type 2 diabetes, Victoza was superior to placebo treatment in reducing HbA1c after 26 weeks (-1.06, ). The treatment difference in HbA1c was 1.3% after additional 26 weeks of open label extension, confirming the sustained glycaemic control with Victoza.

The efficacy and safety profile of Victoza was comparable to that observed in the adult population treated with Victoza. Based on adequate glycaemic control or tolerability, 30% of trial subjects remained on a dose of 0.6 mg, 17% escalated to a dose of 1.2 mg and 53% escalated to a dose of 1.8 mg.

Other clinical data

In an open label trial comparing the efficacy and safety of liraglutide (1.2 mg and 1.8 mg) and sitagliptin (a DPP-4 inhibitor, 100 mg) in patients inadequately controlled on metformin therapy (mean HbA1c 8.5%), liraglutide at both doses was statistically superior to sitagliptin treatment in reducing HbA1c after 26 weeks (-1.24%, -1.50% vs -0.90%, p<0.0001). Patients treated with liraglutide had a significant decrease in body weight compared to that of patients treated with sitagliptin (-2.9 kg and -3.4 kg vs -1.0 kg, p<0.0001). Greater proportions of patients treated with liraglutide experienced transient nausea vs patients treated with sitagliptin (20.8% and 27.1% for liraglutide vs 4.6% for sitagliptin). The reductions in HbA1c and superiority vs sitagliptin observed after 26 weeks of liraglutide treatment (1.2 mg and 1.8 mg) were sustained after 52 weeks of treatment (-1.29% and -1.51% vs -0.88%, p<0.0001). Switching patients from sitagliptin to liraglutide after 52 weeks of treatment resulted in additional and statistically significant reduction in HbA1c (-0.24% and -0.45%, 95% CI: -0.41 to -0.07 and -0.67 to -0.23) at week 78, but a formal control group was not available.

In an open label trial comparing the efficacy and safety of liraglutide 1.8 mg once daily and exenatide 10 mcg twice daily in patients inadequately controlled on metformin and/or sulfonylurea therapy (mean HbA1c 8.3%), liraglutide was statistically superior to exenatide treatment in reducing HbA1c after 26 weeks (-1.12% vs -0.79%; estimated treatment difference: -0.33; 95% CI: -0.47 to -0.18). Significantly more patients achieved HbA1c below 7% with liraglutide compared with exenatide (54.2% vs 43.4%, p=0.0015). Both treatments resulted in mean body weight loss of approximately 3 kg. Switching patients from exenatide to liraglutide after 26 weeks of treatment resulted in an additional and statistically significant reduction in HbA1c (-0.32%, 95% CI: -0.41 to -0.24) at week 40, but a formal control group was not available. During the 26 weeks, there were 12 serious events in 235 patients (5.1%) using liraglutide, whereas there were 6 serious adverse events in 232 patients (2.6%) using exenatide. There was no consistent pattern with respect to system organ class of events.

In an open label trial comparing the efficacy and safety of liraglutide 1.8 mg with lixisenatide 20 mcg in 404 patients inadequately controlled on metformin therapy (mean HbA1c 8.4%), liraglutide was superior to lixisenatide in reducing HbA1c after 26 weeks of treatment (-1.83% vs -1.21%, p<0.0001). Significantly more patients achieved HbA1c below 7% with liraglutide compared to lixisenatide (74.2% vs 45.5%, p<0.0001), as well as the HbA1c target below or equal 6.5% (54.6% vs 26.2%, p<0.0001). Body weight loss was observed in both treatment arms (-4.3 kg with liraglutide and -3.7 kg with lixisenatide). Gastrointestinal adverse events were more frequently reported with liraglutide treatment (43.6% vs 37.1%).

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