In adults with type 2 diabetes

Across 7 clinical trials, 70% of patients lost some weight with Victoza®.1

Victoza® is not indicated for chronic weight management, and weight change was a secondary end point in clinical trials.

-0.4 lb with Victoza® 1.8 mg | +0.7 lb with Victoza® 1.2 mg | +4.6 lb with rosiglitazone 4 mg | -0.2 lb with placebo
 
-6.2 lb with Victoza® 1.8 mg | -5.7 lb with Victoza® 1.2 mg | +2.2 lb with glimepiride 4 mg | -3.3 lb with placebo
 
_____

Victoza® + metformin provided
reductions of up to 17% in visceral fat.4

Victoza® + metformin provided reductions of up to 17% in visceral fat.4

 
-4.4 lb with Victoza® 1.8 mg | -2.2 lb with Victoza® 1.2 mg | +1.3 lb with placebo
 
-7.3 lb with Victoza® 1.8 mg | -5.9 lb with Victoza® 1.2 mg | -1.8 lb with sitagliptin 100 mg
 
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Victoza® offers 3-for-1 benefits.

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Victoza® offers 3-for-1 benefits.

 
 

Safety and tolerability were studied

 

LEAD 1


LEAD 1
  • Hypoglycemia was infrequent with all treatments
 
 

LEAD 2


LEAD 2
  • Nausea was transient in nature
  • No major hypoglycemic events occurred
  • Low rate of minor hypoglycemia
 
 

LEAD 4


LEAD 4
  • Nausea was transient in nature
  • No major hypoglycemic events occurred
  • Low rate of minor hypoglycemia with Victoza®
 
 

Pratley (1860)


Pratley (1860)
  • Nausea occurred more frequently with Victoza® but was transient and the percentage of patients reporting it declined over time
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LEAD 1


LEAD 1

Common adverse reactions
 All Victoza® + glimepiride (N=695)
 glimepiride + rosiglitazone (n=231)
 glimepiride + placebo (n=114)
Nausea
7.5%
2.6%
1.8%
Diarrhea
7.2%
2.2%
1.8%
Constipation
5.3%
1.7%
0.9%
Dyspepsia
5.2%
2.6%
0.9%

  • Hypoglycemia was infrequent with all treatments
  • Hypoglycemia was infrequent with all treatments
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LEAD 4


LEAD 4

Common adverse reactions
 All Victoza® + metformin + rosiglitazone (n=355)
 placebo + metformin + rosiglitazone (n=175)
Nausea
34.6%
8.6%
Diarrhea
14.1%
6.3%
Vomiting
12.4%
2.9%
Headache
8.2%
4.6%
Constipation
5.1%
1.1%

  • Nausea was transient in nature
  • No major hypoglycemic events occurred
  • Low rate of minor hypoglycemia with Victoza®
  • Nausea was transient in nature
  • No major hypoglycemic events occurred
  • Low rate of minor hypoglycemia with Victoza®
 
 

LEAD 2


LEAD 2

Common adverse reactions
 All Victoza® + metformin (n=724)
metformin + placebo (n=121)
 metformin + glimepiride (n=242)
Nausea
15.2%
4.1%
3.3%
Diarrhea
10.9%
4.1%
3.7%
Headache
9.0%
6.6%
9.5%
Vomiting
6.5%
0.8%
0.4%

  • Nausea was transient in nature
  • No major hypoglycemic events occurred
  • Low rate of minor hypoglycemia
  • Nausea was transient in nature
  • No major hypoglycemic events occurred
  • Low rate of minor hypoglycemia
 
 

Pratley (1860)


Pratley (1860)

Common
adverse
reactions
 
Victoza® + metformin (n=439)
metformin + sitagliptin 100 mg (n=219)
Nausea
23.9%
4.6%
Headache
10.3%
10.0%
Diarrhea
9.3%
4.6%
Vomiting
8.7%
4.1%
Minor hypoglycemia
5.0%
5.0%

  • Nausea occurred more frequently with Victoza® but was transient and the percentage of patients reporting it declined over time
  • Nausea occurred more frequently with Victoza® but was transient and the percentage of patients reporting it declined over time
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Study designs

LEAD 1
A 26-week, double-blind, double-dummy, placebo- and active-controlled, 5-armed, parallel trial to compare the efficacy and safety of Victoza®, rosiglitazone, and placebo, all in combination with glimepiride, in type 2 diabetes. Patients with type 2 diabetes (N=1041) were randomized to receive once-daily Victoza® 0.6 mg (n=233), Victoza® 1.2 mg (n=228), Victoza®1.8 mg (n=234), rosiglitazone 4 mga (n=232), or placebo (n=114) in combination with glimepiride (2-4 mg). The primary outcome was change in A1C.2

LEAD 2
A 26-week, double-blind, double-dummy, placebo- and active-controlled, parallel-group, randomized trial to compare the safety and efficacy of Victoza®, glimepiride, and placebo, all in combination with metformin. Patients with type 2 diabetes (N=1091) were randomized to receive Victoza® 0.6 mg (n=242), Victoza® 1.2 mg (n=241), Victoza® 1.8 mg (n=242), glimepiride 4 mga (n=244), or placebo (n=122). The primary end point was change in A1C.3

LEAD 4
A 26-week, double-blind, placebo-controlled, parallel-group, multicenter study to compare the efficacy and safety of Victoza® in combination with rosiglitazone + metformin vs rosiglitazone + metformin. Patients with type 2 diabetes (N=533) were randomized to receive once-daily Victoza® 1.2 mg (n=178), Victoza® 1.8 mg (n=178), or placebo (n=177). The primary outcome was change in A1C.5

Pratley (1860)
A 26-week, open-label, active-comparator, 3-armed, parallel-group trial to compare the efficacy and safety of Victoza® with sitagliptin for the treatment of type 2 diabetes. Patients with type 2 diabetes inadequately controlled on metformin (N=665) were randomized to receive once-daily Victoza® 1.2 mg (n=225), Victoza® 1.8 mg (n=221), or sitagliptin 100 mg (n=219). The primary outcome was change in A1C.6

a4 mg=half the maximal approved dose in the United States.

 

SU=sulfonylurea; TZD=thiazolidinedione.


References: 1. Niswender K, Pi-Sunyer X, Buse J, et al. Weight change with liraglutide and comparator therapies: an analysis of seven phase 3 trials from the liraglutide diabetes development programme. Diabetes Obes Metab. 2013;15(1):42-54. 2. Marre M, Shaw J, Brändle M, et al; on behalf of the LEAD-1 SU study group. Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with type 2 diabetes (LEAD-1 SU). Diabet Med. 2009;26(3):268-278. 3. Nauck M, Frid A, Hermansen K, et al; for the LEAD-2 Study Group. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 2009;32(1):84-90. 4. Jendle J, Nauck MA, Matthews DR, et al; for the LEAD-2 and LEAD-3 Study Groups. Weight loss with liraglutide, a once-daily human glucagon-like peptide-1 analogue for type 2 diabetes treatment as monotherapy or added to metformin, is primarily as a result of a reduction in fat tissue. Diabetes Obes Metab. 2009;11(12):1163-1172. 5. Zinman B, Gerich J, Buse JB, et al; for the LEAD-4 Study Investigators. Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met+TZD). Diabetes Care. 2009;32(7):1224-1230. 6. Pratley RE, Nauck M, Bailey T, et al; for the 1860-LIRA-DPP-4 Study Group. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet. 2010;375(9724):1447-1456.

 

 

Selected Important Safety Information

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 Victoza® 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.
  • Victoza® 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 Victoza® 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 Victoza®.

Victoza® (liraglutide [rDNA origin] injection) Indications and Usage

  • Victoza® (liraglutide [rDNA origin] injection) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Important Limitations of Use

  • Victoza® is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise because of the uncertain relevance of the rodent C-cell tumor findings to humans. Prescribe Victoza® only to patients for whom the potential benefits are considered to outweigh the potential risk.
  • Based on spontaneous postmarketing reports, acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with Victoza®. Victoza® has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using Victoza®. Other antidiabetic therapies should be considered in patients with a history of pancreatitis.
  • Victoza® is not a substitute for insulin. Victoza® should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings.
  • The concurrent use of Victoza® and prandial insulin has not been studied.

Important Safety Information

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 Victoza® 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.
  • Victoza® 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 Victoza® 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 Victoza®.

Contraindications

  • Victoza® is contraindicated in patients with a prior serious hypersensitivity reaction to Victoza® or to any of the product components.

Warnings and Precautions

  • Pancreatitis: Based on spontaneous postmarketing reports, acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with Victoza®. After initiation of Victoza®, observe patients carefully 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, Victoza® should promptly be discontinued and appropriate management should be initiated. If pancreatitis is confirmed, Victoza® should not be restarted. Consider antidiabetic therapies other than Victoza® in patients with a history of pancreatitis.
  • Never Share a Victoza® Pen Between Patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens.
  • Use with Medications Known to Cause Hypoglycemia: When Victoza® is used with an insulin secretagogue (e.g. a sulfonylurea) or insulin, serious hypoglycemia can occur. Consider lowering the dose of the insulin secretagogue or insulin to reduce the risk of hypoglycemia.
  • Renal Impairment: Renal impairment has been reported postmarketing, usually in association with nausea, vomiting, diarrhea, or dehydration, which may sometimes require hemodialysis. Use caution when initiating or escalating doses of Victoza® in patients with renal impairment.
  • Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g. anaphylaxis and angioedema) have been reported postmarketing. If symptoms of hypersensitivity reactions occur, patients must stop taking Victoza® and seek medical advice promptly.
  • Macrovascular Outcomes: There have been no studies establishing conclusive evidence of macrovascular risk reduction with Victoza® or any other antidiabetic drug.

Adverse Reactions

  • The most common adverse reactions, reported in ≥5% of patients treated with Victoza® and more commonly than in patients treated with placebo, are headache, nausea, diarrhea, dyspepsia, constipation, and anti-liraglutide antibody formation. Immunogenicity-related events, including urticaria, were more common among Victoza®-treated patients (0.8%) than among comparator-treated patients (0.4%) in clinical trials.

Use in Specific Populations

  • Victoza® has not been studied in patients with type 2 diabetes below 18 years of age and is not recommended for use in pediatric patients.
  • There is limited data in patients with renal or hepatic impairment.

Additional Important Safety Information

Victoza® is not indicated for chronic weight management, and weight change was a secondary end point in clinical trials.

GLP-1 (7-37) represents <20% of total circulating endogenous GLP-1.

In a 52-week monotherapy study (N=745) with a 52-week extension, the adverse reactions reported in ≥5% of patients treated with Victoza® 1.8 mg, Victoza® 1.2 mg, or glimepiride were constipation (11.8%, 8.4%, and 4.8%), diarrhea (19.5%, 17.5%, and 9.3%), flatulence (5.3%, 1.6%, and 2.0%), nausea (30.5%, 28.7%, and 8.5%), vomiting (10.2%, 13.1%, and 4.0%), fatigue (5.3%, 3.2%, and 3.6%), bronchitis (3.7%, 6.0%, and 4.4%), influenza (11.0%, 9.2%, and 8.5%), nasopharyngitis (6.5%, 9.2%, and 7.3%), sinusitis (7.3%, 8.4%, and 7.3%), upper respiratory tract infection (13.4%, 14.3%, and 8.9%), urinary tract infection (6.1%, 10.4%, and 5.2%), arthralgia (2.4%, 4.4%, and 6.0%), back pain (7.3%, 7.2%, and 6.9%), pain in extremity (6.1%, 3.6%, and 3.2%), dizziness (7.7%, 5.2%, and 5.2%), headache (7.3%, 11.2%, and 9.3%), depression (5.7%, 3.2%, and 2.0%), cough (5.7%, 2.0%, and 4.4%), and hypertension (4.5%, 5.6%, and 6.9%).

In a 52-week monotherapy study (N=745), the adverse reactions reported in ≥5% of patients treated with Victoza® or ≥5% of patients treated with glimepiride were nausea (28.4% vs 8.5%), diarrhea (17.1% vs 8.9%), vomiting (10.9% vs 3.6%), constipation (9.9% vs 4.8%), upper respiratory tract infection (9.5% vs 5.6%), headache (9.1% vs 9.3%), influenza (7.4% vs 3.6%), urinary tract infection (6.0% vs 4.0%), dizziness (5.8% vs 5.2%), sinusitis (5.6% vs 6.0%), nasopharyngitis (5.2% vs 5.2%), back pain (5.0% vs 4.4%), and hypertension (3.0% vs 6.0%).

Adverse reactions reported in ≥5% of patients and occurring more frequently with Victoza® compared to exenatide were diarrhea (12.3% vs 12.1%), dyspepsia (8.9% vs 4.7%), and constipation (5.1% vs 2.6%). Rates of gastrointestinal adverse reactions, including nausea, were similar.

In a 26-week study (N=323) of Victoza® 1.8 mg and intensification with insulin detemir, the only adverse reaction reported in ≥5% of the patients treated with Victoza® 1.8 mg + metformin + insulin detemir and greater than in patients treated with Victoza® 1.8 mg + metformin alone was diarrhea (11.7% vs 6.9%).

In a 26-week open-label study (N=665) comparing Victoza® 1.2 mg, Victoza® 1.8 mg, and sitagliptin 100 mg, all in combination with metformin, the adverse reactions reported in ≥5% of the patients treated with Victoza® were nausea (23.9% vs 4.6%), headache (10.3% vs 10.0%), diarrhea (9.3% vs 4.6%), and vomiting (8.7% vs 4.1%).

In a 26-week open-label study (N=665) with a 26-week extension (N=497), the adverse reactions reported in ≥5% of patients treated with metformin in combination with Victoza® 1.2 mg or Victoza® 1.8 mg or sitagliptin 100 mg were nausea (21.7%, 27.5%, and 5.5%), vomiting (8.1%, 10.6%, and 5.0%), diarrhea (9.0%, 12.4%, and 6.4%), and headache (9.5%, 13.3%, and 12.3%).

The most common adverse events occurring in 5% or more of patients in the treatment groups combined (Victoza® 1.8 mg vs exenatide ER 2 mg): nausea (21% vs 9%); diarrhea (13% vs 6%); headache (8% vs 6%); vomiting (11% vs 4%); nasopharyngitis (7% vs 7%); injection-site nodule (1% vs 10%); decreased appetite (6% vs 4%); constipation (5% vs 5%); dyspepsia (6% vs 2%); unexpected therapeutic response (6% vs 2%); and minor hypoglycemia in patients not taking concomitant sulfonylurea (3% vs 4%).

The most common adverse events occurring in 5% or more of patients in the treatment groups combined (Victoza® 1.8 mg vs albiglutide 50 mg): diarrhea (14% vs 15%); upper respiratory tract infection (11% vs 10%); nausea (29% vs 10%); injection-site reaction (1% vs 7%); urinary tract infection (6% vs 6%); nasopharyngitis (7% vs 6%); increased lipase concentration (7% vs 5%); headache (5% vs 5%); vomiting (9% vs 5%); and minor hypoglycemia (13% vs 10%). No major hypoglycemia occurred.

The HARMONY 7 trial included data from the Pancreatitis Adjudication Committee:

  • During the study itself, the Pancreatitis Adjudication Committee undertook masked adjudication of possible events of pancreatitis
  • Of these patients, 1 person in the albiglutide group and 2 in the Victoza® group were judged to have definite or probable pancreatitis that was at least possibly related to study treatment
  • The remaining cases were adjudicated as possible pancreatitis based on lipase elevation alone (11 albiglutide, 8 Victoza®) or unlikely (1 Victoza®)

The most common adverse events occurring in 5% or more of patients in the treatment groups combined (Victoza® 1.8 mg vs dulaglutide 1.5 mg): nausea (18% vs 20%); diarrhea (12% vs 12%); vomiting (8% vs 7%); dyspepsia (6% vs 8%); constipation (6% vs 4%); nasopharyngitis (7% vs 8%); headache (8% vs 7%); back pain (5% vs 4%); decreased appetite (7% vs 5%); and minor hypoglycemia (6% vs 9%). No major hypoglycemia occurred.

Counsel patients regarding the risk for MTC and the symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea or persistent hoarseness).

Patients with thyroid nodules noted on physical examination or neck imaging obtained for other reasons should be referred to an endocrinologist for further evaluation.

Although routine monitoring of serum calcitonin is of uncertain value in patients treated with Victoza®, if serum calcitonin is measured and found to be elevated, the patient should be referred to an endocrinologist for further evaluation.

After initiation of Victoza®, and after dose increases, observe patients carefully 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).

In the eight clinical trials of at least 26 weeks duration, hypoglycemia requiring the assistance of another person for treatment occurred in 11 Victoza®-treated patients and in two exenatide-treated patients. Of these 11 Victoza®-treated patients, six patients were concomitantly using metformin and a sulfonylurea, one was concomitantly using a sulfonylurea, two were concomitantly using metformin and two were using Victoza® as monotherapy. In the 26-week open-label trial comparing Victoza® to sitagliptin, the incidence of hypoglycemic events was comparable among the treatment groups.

The incidence of withdrawal due to adverse events was 7.8% for Victoza®-treated patients and 3.4% for comparator-treated patients in the 5 controlled trials of 26 weeks duration or longer. This difference was driven by withdrawals due to gastrointestinal adverse reactions, which occurred in 5.0% of Victoza®-treated patients and 0.5% of comparator-treated patients. The most common adverse reactions leading to withdrawal for Victoza®-treated patients were nausea (2.8% versus 0% for comparator) and vomiting (1.5% versus 0.1% for comparator).

Victoza® causes a delay in gastric emptying, and thereby has the potential to impact absorption of concomitantly administered oral medications. Caution should be exercised when oral medications are concomitantly administered with Victoza®.

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

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