Victoza® is unsurpassed in reducing A1C across these multiple studies in adults with type 2 diabetes.


Mean change in A1C (%)


LEAD 4 vs metformin +TZD1

Zinman: 
Victoza® + metformin +
TZD vs metformin + TZD

Baseline A1C 8.4% to 8.6%

Victoza® 1.8 mg (n=178)
Victoza® 1.2 mg (n=177)

Placebo (n=175)

LEAD 4 vs. metformin + TZD
 
Pratley (1860) vs sitagliptin2

Pratley (1860): 
Victoza® + metformin
vs sitagliptin + metformin

Baseline A1C 8.4% to 8.5%

Victoza® 1.8 mg (n=218)
Victoza® 1.2 mg (n=221)

sitagliptin 100 mg (n=219)

Pratley (1860) vs. sitagliptin
 
LEAD 1 vs TZD3,g

Marre: 
Victoza® + SU vs TZD + SU

Baseline A1C 8.4% to 8.5%

Victoza® 1.8 mg (n=234)
Victoza® 1.2 mg (n=228)

rosiglitazone 4 mg (n=231)
Placebo (n=114)

 
LEAD 1 vs. TZD
 
LEAD 2 vs glimepiride4,g

Nauck: 
Victoza® + metformin vs glimepiride + metformin

Baseline A1C 8.3% to 8.4%

Victoza® 1.8 mg (n=242)
Victoza® 1.2 mg (n=240)

glimepiride 4 mg (n=242)
Placebo (n=121)

LEAD 2 vs. glimepiride
 


Weight change: An additional benefit of Victoza®

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


Safety and tolerability were studied

LEAD 4


Lead 4 AE

Nausea was transient.1
No major hypoglycemic events occurred.1
Low rate of minor hypoglycemia with Victoza®.1

Pratley (1860)


Pratley AE

Nausea occurred more frequently with Victoza® but was transient, and the percentage of patients reporting it declined over time.2

LEAD 1


Lead 1 AE

Hypoglycemia was infrequent with all treatments.3

LEAD 2


Lead 2 AE

Nausea was transient.4
No major hypoglycemic events occurred.4
Low rate of minor hypoglycemia compared with glimepiride.4


aP<0.0001 vs placebo.
bETD Victoza® 1.2 mg vs placebo: -0.9%, 95% CI (-1.1, -0.8).1
c
ETD Victoza® 1.8 mg vs placebo: -1.1%, 95% CI (-1.1, -0.8).1
d
P<0.0001 vs comparator.
eETD Victoza® 1.2 mg vs sitagliptin 100 mg: -0.3, 95% CI (-0.5, -0.2).
fETD Victoza® 1.8 mg vs sitagliptin 100 mg: -0.6, 95% CI (-0.8, -0.4).
gGlimepiride and rosiglitazone were given at half the maximal US-approved dose.
hVictoza® 1.2 mg and 1.8 mg were superior to rosiglitazone. ETD for Victoza® 1.2 mg vs placebo: -1.3%, 95% CI (1.5, -1.1); Victoza® 1.8 mg vs placebo: -1.4%, 95% CI (1.6, -1.1).3
i
ETD for both Victoza® 1.2 mg and 1.8 mg: 0.0%, 95% CI (-0.2, 0.2).4


Establishing Noninferiority/Superiority2,5-7:
In LEAD 1 and Pratley (1860), A1C was analyzed using hierarchical testing. In LEAD 1 and Pratley (1860), noninferiority of Victoza® 1.8 mg and 1.2 mg to active comparator (rosiglitazone and sitagliptin) was established first. Then superiority of the 2 therapeutic doses of Victoza® vs active comparator was demonstrated. In LEAD 4, superiority of Victoza® 1.8 mg and 1.2 mg + metformin and TZD vs placebo + metformin was demonstrated; therefore, equivalence testing was precluded. In LEAD 2, superiority of all doses of Victoza® vs placebo was demonstrated and so too was noninferiority of Victoza® 1.2 mg and 1.8 mg vs glimepiride.

Superiority of glycemic control with Victoza® vs placebo/active comparator was concluded if the upper limit of the 2-sided 95% CI for the treatment difference was <0%; noninferiority was concluded if the upper limit was <0.4%.    


In adults with type 2 diabetes

As monotherapy, Victoza® provides early and lasting change in A1C.

A1C reductions were sustained for 104 weeks8,9

A chart showing reductions in the A1C level of type 2 diabetes patients.

Plot points on the above chart represent ITT, observed data.
End values represent completer patients.
Victoza® is not recommended as first-line therapy in patients inadequately controlled on diet and exercise.

Additional results


Additional results for A1C reductions after 1 year

jP=0.0014 vs glimepiride.
kP<0.0001 vs glimepiride.

 

Safety and tolerability were studied

  • Occurrence of nausea remained low and was transient9
  • One event of major hypoglycemia (Victoza® 1.8 mg) occurred after regular insulin was infused as part of a substudy procedure9
  • 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%)8


Get to know Victoza®


A1C by baseline

Victoza® offers A1C reductions in adults with type 2 diabetes with baseline A1C from 7.5% to 10%.10

Victoza® samples

Licensed practitioners can register to receive complimentary Victoza® samples.

 

Study designs

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.1

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.2

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 mgl (n=232), or placebo (n=114) in combination with glimepiride (2-4 mg). The primary outcome was change in A1C.3

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 mgl (n=244), or placebo (n=122). The primary endpoint was change in A1C.4
 

LEAD 3
A 52-week, double-blind, double-dummy, active-controlled, parallel-group, multicenter study. Patients with type 2 diabetes (N=746) were randomized to receive once-daily Victoza® 1.2 mg (n=251), Victoza® 1.8 mg (n=246), or glimepiride 8 mg (n=248). The primary outcome was change in A1C after 52 weeks. 11
 

LEAD 3 Extension
A 52-week, open-label extension study of LEAD 3. Completer patients with type 2 diabetes (N=440) continued on Victoza® 1.2 mg (n=149), Victoza® 1.8 mg (n=154), or glimepiride 8 mg (n=137) following a 52-week, double-blind, double-dummy, active-controlled, parallel-group, multicenter study. The key efficacy variable of the open-label extension was change in A1C from baseline after 104 weeks.9


l4 mg=half the maximal approved dose in the United States.
CI=confidence interval; ETD=estimated treatment difference; SU=sulfonylurea; TZD=thiazolidinedione; ITT=intent-to-treat.


References: 
1. 
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. 2. 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. 3. 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. 4. 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. 5. Novo Nordisk Inc. Liraglutide effect and action in diabetes (LEAD-1): effect on glycaemic control after once daily administration of liraglutide in combination with glimepiride versus glimepiride monotherapy versus glimepiride and rosiglitazone combination therapy in subjects with type 2 diabetes. Clinical Trial Report. February 15, 2008. 6. Novo Nordisk Inc. Liraglutide effect and action in diabetes (LEAD-2): effect on glycaemic control after once daily administration of liraglutide in combination with metformin versus metformin monotherapy versus metformin and glimepiride combination therapy in subjects with type 2 diabetes. Clinical Trial Report. February 5, 2008. 7. Novo Nordisk Inc. Liraglutide effect and action in diabetes (LEAD-4): effect on glycaemic control of liraglutide in combination with rosiglitazone plus metformin versus rosiglitazone plus metformin in type 2 diabetes (a twenty-six week double-blind parallel trial to investigate safety and efficacy). Clinical Trial Report. February 1, 2008. 8. Novo Nordisk Inc. Liraglutide effect and action in diabetes (LEAD 3): effect on glycemic control of liraglutide versus glimepiride in type 2 diabetes [a fifty-two week (with fifty-two week open-label extension) double-blind, multicenter, randomized, parallel study to investigate safety and efficacy]. Clinical Trial Report. March 6, 2009. 9. Garber A, Henry RR, Ratner R, Hale P, Chang CT, Bode B; on behalf of the LEAD-3 (Mono) Study Group. Liraglutide, a once-daily human glucagon-like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes. Diabetes Obes Metab. 2011;13(4):348-356. 10. Pratley R, Nauck M, Bailey T, et al; for the 1860-LIRA-DPP-4 Study Group. One year of liraglutide treatment offers sustained and more effective glycaemic control and weight reduction compared with sitagliptin, both in combination with metformin, in patients with type 2 diabetes: a randomised, parallel-group, open-label trial. Int J Clin Pract. 2011;65(4):397-407. 11. Garber A, Henry R, Ratner R, et al; for the LEAD-3 (Mono) Study Group. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009;373(9662):473-481. 

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®.

Indication and Limitations of Use

Victoza® (liraglutide) injection 1.2 mg or 1.8 mg is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, and to reduce the risk of major adverse cardiovascular (CV) events (CV death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus and established CV disease.

  • Victoza® is not a substitute for insulin and should not be used in patients with type 1 diabetes mellitus or diabetic ketoacidosis.
  • Concurrent use with 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 personal or family history of MTC or in patients with MEN 2, and in patients with a prior serious hypersensitivity reaction to Victoza® or to any of the product components. Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with Victoza®.

Warnings and Precautions

  • Risk of Thyroid C-cell Tumors: Patients should be referred to an endocrinologist for further evaluation if serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging.
  • Pancreatitis: Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with Victoza® postmarketing. Observe patients carefully for signs and symptoms of pancreatitis (persistent severe abdominal pain, sometimes radiating to the back with or without vomiting). If pancreatitis is suspected, discontinue Victoza® promptly and if pancreatitis is confirmed, do not restart. Victoza® has been studied in a limited number of patients with a history of pancreatitis. It is unknown if patients with a history of pancreatitis are at a higher risk for development of pancreatitis on Victoza®.
  • Never Share a Victoza® Pen Between Patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens.
  • Hypoglycemia: When Victoza® is used with an insulin secretagogue (eg, 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: Acute renal failure and worsening of chronic renal failure, which may sometimes require hemodialysis, have been reported postmarketing, usually in association with nausea, vomiting, diarrhea, or dehydration. Use caution when initiating or escalating doses of Victoza® in patients with renal impairment.
  • Hypersensitivity Reactions: Serious hypersensitivity reactions (eg, anaphylaxis and angioedema) have been reported post-marketing. If symptoms of hypersensitivity reactions occur, patients must stop taking Victoza®; treat promptly per standard of care, and monitor until signs and symptoms resolve.  Do not use in patients with a previous hypersensitivity reaction to Victoza®. Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists.  Use caution in a patient with a history of anaphylaxis or angioedema with another GLP-receptor agonist because it is unknown whether such patients will be predisposed to these reactions with Victoza®.
  • Acute Gallbladder Disease: In the LEADER trial, 3.1% of Victoza® vs. 1.9% of placebo-treated patients reported an acute event of gallbladder disease, such as cholelithiasis or cholecystitis. The majority of events required hospitalization or cholecystectomy. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow up are indicated.

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 nausea, diarrhea, headache, vomiting, decreased appetite, dyspepsia, and constipation. Immunogenicity-related events, including urticaria, were more common among Victoza®-treated patients (0.8%) than among comparator-treated patients (0.4%) in clinical trials.

Drug Interactions

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

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.
  • Victoza® slows gastric emptying. Victoza® has not been studied in patients with pre-existing gastroparesis.
  • Victoza® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Additional Important Safety Information

In 5 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.

In the pool of 5 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 to 3 months of the trials.

Please click here for Prescribing Information.