Victoza

1 

ss 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 



 2 

1. NAME OF THE MEDICINAL PRODUCT 
 
Victoza 6 mg/ml solution for injection in pre-filled pen 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
1 ml of solution contains 6 mg of liraglutide*. One pre-filled pen contains 18 mg liraglutide in 3 ml. 
 
* human glucagon-like peptide-1 (GLP-1) analogue produced by recombinant DNA technology in 
Saccharomyces cerevisiae. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection. 
Clear and colourless or almost colourless, isotonic solution; pH=8.15. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Victoza is indicated for the treatment of adults, adolescents and children aged 10 years and above with 
insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise 
• as monotherapy when metformin is considered inappropriate due to intolerance or 

contraindications 
• in addition to other medicinal products for the treatment of diabetes. 
For study results with respect to combinations, effects on glycaemic control and cardiovascular events, 
and the populations studied, see sections 4.4, 4.5 and 5.1. 
 
4.2 Posology and method of administration 
 
Posology 
 
To improve gastro-intestinal tolerability, the starting dose is 0.6 mg liraglutide daily. After at least one 
week, the dose should be increased to 1.2 mg. Some patients are expected to benefit from an increase 
in dose from 1.2 mg to 1.8 mg and based on clinical response, after at least one week, the dose can be 
increased to 1.8 mg to further improve glycaemic control. Daily doses higher than 1.8 mg are not 
recommended. 
 
When Victoza is added to a sulfonylurea or insulin, a reduction in the dose of sulfonylurea or insulin 
should be considered to reduce the risk of hypoglycaemia (see section 4.4). Combination therapy with 
sulfonylurea is only valid for adult patients. 
 
Self-monitoring of blood glucose is not needed in order to adjust the dose of Victoza. Blood glucose 
self-monitoring is necessary to adjust the dose of sulfonylurea and insulin, particularly when Victoza 
therapy is started and insulin is reduced. A stepwise approach to insulin dose reduction is 
recommended.  
 
Special populations 
 
Elderly patients (>65 years old) 
No dose adjustment is required based on age (see section 5.2). 
 



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Renal impairment 
No dose adjustment is required for patients with mild, moderate or severe renal impairment. There is 
no therapeutic experience in patients with end-stage renal disease, and Victoza is therefore not 
recommended for use in these patients (see sections 5.1 and 5.2). 
 
Hepatic impairment 
No dose adjustment is recommended for patients with mild or moderate hepatic impairment. Victoza 
is not recommended for use in patients with severe hepatic impairment (see section 5.2).  
 
Paediatric population 
No dose adjustment is required for adolescents and children aged 10 years and above. No data are 
available for children below 10 years of age (see sections 5.1 and 5.2).  
 
Method of administration 
 
Victoza must not be administered intravenously or intramuscularly. 
 
Victoza is administered once daily at any time, independent of meals, and can be injected 
subcutaneously in the abdomen, in the thigh or in the upper arm. The injection site and timing can be 
changed without dose adjustment. However, it is preferable that Victoza is injected around the same 
time of the day, when the most convenient time of the day has been chosen. For further instructions on 
administration, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Liraglutide should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic 
ketoacidosis. 
 
Liraglutide is not a substitute for insulin. Diabetic ketoacidosis has been reported in insulin-dependent 
patients after rapid discontinuation or dose reduction of insulin (see section 4.2).  
 
There is no therapeutic experience in patients with congestive heart failure New York Heart 
Association (NYHA) class IV, and liraglutide is therefore not recommended for use in these patients. 
 
There is limited experience in patients with inflammatory bowel disease and diabetic gastroparesis. 
Use of liraglutide is not recommended in these patients since it is associated with transient 
gastrointestinal adverse reactions, including nausea, vomiting and diarrhoea.  
 
Acute pancreatitis 
 
Acute pancreatitis has been observed with the use of GLP-1 receptor agonists. Patients should be 
informed of the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, liraglutide 
should be discontinued; if acute pancreatitis is confirmed, liraglutide should not be restarted (see 
sections 4.8 and 5.1). 
 
Thyroid disease 
 
Thyroid adverse events, such as goitre, have been reported in clinical trials and in particular in patients 
with pre-existing thyroid disease. Liraglutide should therefore be used with caution in these patients. 
 
Hypoglycaemia 
 
Patients receiving liraglutide in combination with a sulfonylurea or insulin may have an increased risk 



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of hypoglycaemia (see section 4.8). The risk of hypoglycaemia can be lowered by a reduction in the 
dose of sulfonylurea or insulin. 
 
Dehydration 
 
Signs and symptoms of dehydration, including renal impairment and acute renal failure, have been 
reported in patients treated with liraglutide. Patients treated with liraglutide should be advised of the 
potential risk of dehydration in relation to gastrointestinal side effects and take precautions to avoid 
fluid depletion. 
 
Excipients 
 
Victoza contains less than 1 mmol sodium (23 mg) per dose, therefore the medicinal product is 
essentially ‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
In vitro, liraglutide has shown very low potential to be involved in pharmacokinetic interactions with 
other active substances related to cytochrome P450 and plasma protein binding. 
 
The small delay of gastric emptying with liraglutide may influence absorption of concomitantly 
administered oral medicinal products. Interaction studies did not show any clinically relevant delay of 
absorption and therefore no dose adjustment is required. Few patients treated with liraglutide reported 
at least one episode of severe diarrhoea. Diarrhoea may affect the absorption of concomitant oral 
medicinal products. 
 
Warfarin and other coumarin derivatives 
 
No interaction study has been performed. A clinically relevant interaction with active substances with 
poor solubility or with narrow therapeutic index such as warfarin cannot be excluded. Upon initiation 
of liraglutide treatment in patients on warfarin or other coumarin derivatives, more frequent 
monitoring of INR (International Normalised Ratio) is recommended. 
 
Paracetamol 
 
Liraglutide did not change the overall exposure of paracetamol following a single dose of 1000 mg. 
Paracetamol Cmax was decreased by 31% and median tmax was delayed up to 15 min. No dose 
adjustment for concomitant use of paracetamol is required. 
 
Atorvastatin 
 
Liraglutide did not change the overall exposure of atorvastatin to a clinically relevant degree following 
single dose administration of atorvastatin 40 mg. Therefore, no dose adjustment of atorvastatin is 
required when given with liraglutide. Atorvastatin Cmax was decreased by 38% and median tmax was 
delayed from 1 h to 3 h with liraglutide. 
 
Griseofulvin 
 
Liraglutide did not change the overall exposure of griseofulvin following administration of a single 
dose of griseofulvin 500 mg. Griseofulvin Cmax increased by 37% while median tmax did not change. 
Dose adjustments of griseofulvin and other compounds with low solubility and high permeability are 
not required. 
 
Digoxin 
 
A single dose administration of digoxin 1 mg with liraglutide resulted in a reduction of digoxin AUC 
by 16%; Cmax decreased by 31%. Digoxin median tmax was delayed from 1 h to 1.5 h. No adjustment of 



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digoxin dose is required based on these results. 
 
Lisinopril 
 
A single dose administration of lisinopril 20 mg with liraglutide resulted in a reduction of lisinopril 
AUC by 15%; Cmax decreased by 27%. Lisinopril median tmax was delayed from 6 h to 8 h with 
liraglutide. No dose adjustment of lisinopril is required based on these results. 
 
Oral contraceptives 
 
Liraglutide lowered ethinyloestradiol and levonorgestrel Cmax by 12 and 13%, respectively, following 
administration of a single dose of an oral contraceptive product. Tmax was delayed by 1.5 h with 
liraglutide for both compounds. There was no clinically relevant effect on the overall exposure of 
either ethinyloestradiol or levonorgestrel. The contraceptive effect is therefore anticipated to be 
unaffected when co-administered with liraglutide. 
 
Insulin 
 
No pharmacokinetic or pharmacodynamic interactions were observed between liraglutide and insulin 
detemir when administering a single dose of insulin detemir 0.5 U/kg with liraglutide 1.8 mg at steady 
state in patients with type 2 diabetes. 
 
Paediatric Population 
 
Interaction studies have only been performed in adults.  
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no adequate data from the use of liraglutide in pregnant women. Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. 
 
Liraglutide should not be used during pregnancy, and the use of insulin is recommended instead. If a 
patient wishes to become pregnant, or pregnancy occurs, treatment with Victoza should be 
discontinued. 
 
Breast-feeding 
 
It is not known whether liraglutide is excreted in human milk. Animal studies have shown that the 
transfer of liraglutide and metabolites of close structural relationship into milk is low. Non-clinical 
studies have shown a treatment-related reduction of neonatal growth in suckling rat pups (see section 
5.3). Because of lack of experience, Victoza should not be used during breast-feeding. 
 
Fertility 
 
Apart from a slight decrease in the number of live implants, animal studies did not indicate harmful 
effects with respect to fertility. 
 
4.7 Effects on ability to drive and use machines 
 
Victoza has no or negligible influence on the ability to drive and use machines. 
Patients should be advised to take precautions to avoid hypoglycaemia while driving and using 
machines, in particular when Victoza is used in combination with a sulfonylurea or insulin. 
 
4.8 Undesirable effects 
 



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Summary of the safety profile 
 
In five large long-term clinical phase 3a trials over 2,500 adult patients have received treatment with 
Victoza alone or in combination with metformin, a sulfonylurea (with or without metformin) or 
metformin plus rosiglitazone. 
 
The most frequently reported adverse reactions during clinical trials were gastrointestinal disorders: 
nausea and diarrhoea were very common, whereas vomiting, constipation, abdominal pain, and 
dyspepsia were common. At the beginning of the therapy, these gastrointestinal adverse reactions may 
occur more frequently. These reactions usually diminish within a few days or weeks on continued 
treatment. Headache and nasopharyngitis were also common. Furthermore, hypoglycaemia was 
common, and very common when liraglutide is used in combination with a sulfonylurea. Severe 
hypoglycaemia has primarily been observed when combined with a sulfonylurea. 
 
Tabulated list of adverse reactions 
 
Table 1 lists adverse reactions reported in long-term phase 3a controlled trials, the LEADER trial (a 
long-term cardiovascular outcome trial) and spontaneous (post-marketing) reports. Frequencies for all 
events have been calculated based on their incidence in phase 3a clinical trials. 
Frequencies are defined as: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 
to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from 
the available data). Within each frequency grouping, adverse reactions are presented in order of 
decreasing seriousness. 
 
Table 1 Adverse reactions from long-term controlled phase 3a trials, the long-term 

cardiovascular outcome trial (LEADER) and spontaneous (post-marketing) reports 
 

MedDRA 
system organ 
classes 

Very common Common Uncommon Rare Very rare 

Infections and 
infestations 

 Nasopharyngitis 
Bronchitis 

   

Immune 
system 
disorders 

   Anaphylactic 
reactions 

 

Metabolism 
and nutrition 
disorders 

 Hypoglycaemia 
Anorexia 
Appetite decreased 

Dehydration   

Nervous 
system 
disorders 

 Headache 
Dizziness 

   

Cardiac 
disorders 

 Increased heart rate    

Gastrointestina
l disorders 

Nausea 
Diarrhoea 

Vomiting 
Dyspepsia 
Abdominal pain 
upper 
Constipation 
Gastritis 
Flatulence 
Abdominal 
distension 
Gastroesophageal 
reflux disease 
Abdominal 
discomfort 
Toothache 

Delayed 
gastric 
emptying 

Intestinal 
obstruction 

Pancreatitis 
(including 
necrotising 
pancreatitis) 

Hepatobiliary 
disorders 

  Cholelithiasis 
Cholecystitis 

  



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Skin and 
subcutaneous 
tissue disorder 

 Rash Urticaria 
Pruritus 

  

Renal and 
urinary 
disorders 

  Renal 
impairment 
Renal failure 
acute 

  

General 
disorders and 
administration 
site conditions 

 Fatigue 
Injection site 
reactions 

Malaise   

Investigations  Increased lipase* 
Increased amylase* 

   

* From controlled phase 3b and 4 clinical trials only where they were measured. 
 
Description of selected adverse reactions 
 
In a clinical trial with liraglutide as monotherapy, rates of hypoglycaemia reported with liraglutide 
were lower than rates reported for patients treated with active comparator (glimepiride). The most 
frequently reported adverse reactions were gastrointestinal disorders, infections and infestations. 
 
Hypoglycaemia 
Most episodes of confirmed hypoglycaemia in clinical trials were minor. No episodes of severe 
hypoglycaemia were observed in the trial with liraglutide used as monotherapy. Severe hypoglycaemia 
may occur uncommonly and has primarily been observed when liraglutide is combined with a 
sulfonylurea (0.02 events/patient year). Very few episodes (0.001 events/patient year) were observed 
with administration of liraglutide in combination with oral antidiabetics other than sulfonylureas. The 
risk of hypoglycaemia is low with combined use of basal insulin and liraglutide (1.0 events per patient 
year, see section 5.1). In the LEADER trial, severe hypoglycaemic episodes were reported at a lower 
rate with liraglutide vs placebo (1.0 vs 1.5 events per 100 patient years; estimated rate ratio 0.69 [0.51 
to 0.93]) (see section 5.1). For patients treated with premix insulin at baseline and at least for the 
following 26 weeks, the rate of severe hypoglycaemia for both liraglutide and placebo was 2.2 events 
per 100 patient years. 
 
Gastrointestinal adverse reactions 
When combining liraglutide with metformin, 20.7% of patients reported at least one episode of 
nausea, and 12.6% of patients reported at least one episode of diarrhoea. When combining liraglutide 
with a sulfonylurea, 9.1% of patients reported at least one episode of nausea and 7.9% of patients 
reported at least one episode of diarrhoea. Most episodes were mild to moderate and occurred in a 
dose-dependent fashion. With continued therapy, the frequency and severity decreased in most 
patients who initially experienced nausea. 
 
Patients >70 years may experience more gastrointestinal effects when treated with liraglutide. 
Patients with mild and moderate renal impairment (creatinine clearance 60–90 ml/min and 30–
59 ml/min, respectively) may experience more gastrointestinal effects when treated with liraglutide. 
 
Cholelithiasis and cholecystitis 
Few cases of cholelithiasis (0.4%) and cholecystitis (0.1%) have been reported during long-term, 
controlled phase 3a clinical trials with liraglutide. In the LEADER trial, the frequency of cholelithiasis 
and cholecystitis was 1.5% and 1.1% for liraglutide and 1.1% and 0.7% for placebo, respectively (see 
section 5.1). 
 
Withdrawal 
The incidence of withdrawal due to adverse reactions was 7.8% for liraglutide-treated patients and 
3.4% for comparator-treated patients in the long-term controlled trials (26 weeks or longer). The most 
frequent adverse reactions leading to withdrawal for liraglutide-treated patients were nausea (2.8% of 
patients) and vomiting (1.5%). 
 



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Injection site reactions 
Injection site reactions have been reported in approximately 2% of patients receiving Victoza in long-
term (26 weeks or longer) controlled trials. These reactions have usually been mild. 
 
Pancreatitis 
Few cases of acute pancreatitis (<0.2%) have been reported during long-term, controlled phase 3 
clinical trials with Victoza. Pancreatitis was also reported from marketed use. In the LEADER trial, 
the frequency of acute pancreatitis confirmed by adjudication was 0.4% for liraglutide and 0.5% for 
placebo, respectively (see sections 4.4 and 5.1). 
 
Allergic reactions 
Allergic reactions including urticaria, rash and pruritus have been reported from marketed use of 
Victoza. 
Few cases of anaphylactic reactions with additional symptoms such as hypotension, palpitations, 
dyspnoea and oedema have been reported with marketed use of Victoza. Few cases (0.05%) of 
angioedema have been reported during all long-term clinical trials with Victoza. 
 
Paediatric population 
Overall, frequency, type and severity of adverse reactions in adolescents and children aged 10 years 
and above were comparable to that observed in the adult population. Rate of confirmed 
hypoglycaemic episodes was higher with liraglutide (0.58 events/patient year) compared to placebo 
(0.29 events/patient year). In patients treated with insulin prior to a confirmed hypoglycaemic episode 
the rate was higher with liraglutide (1.82 events/patient year) compared to placebo (0.91 events/patient 
years). No severe hypoglycaemic episodes occurred in the liraglutide treatment group.  
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
From clinical trials and marketed use, overdoses have been reported of up to 40 times (72 mg) the 
recommended maintenance dose. Generally, the patients reported severe nausea, vomiting and 
diarrhoea. None of the patients reported severe hypoglycaemia. All patients recovered without 
complications. 
In the event of overdose, appropriate supportive treatment should be initiated according to the 
patient’s clinical signs and symptoms. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
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 

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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). 
 



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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) 
 

 N Mean 
baseline 
HbA1c (%) 

Mean HbA1c 
change from 
baseline (%) 

Patients (%) 
achieving 
HbA1c<7% 

Mean 
baseline 
weight (kg) 

Mean 
weight 
change from 
baseline 
(kg) 

Monotherapy 
Liraglutide 1.2 mg 251 8.18 -0.84* 42.81, 58.33 92.1 -2.05** 
Liraglutide 1.8 mg 246 8.19 -1.14** 50.91, 62.03 92.6 -2.45** 
Glimepiride 8 mg/day 248 8.23 -0.51 27.81, 30.83 93.3 1.12 
Add-on to metformin (2,000 mg/day) 
Liraglutide 1.2 mg 240 8.3 -0.97† 35.31, 52.82 88.5 -2.58** 
Liraglutide 1.8 mg 242 8.4 -1.00† 42.41, 66.32 88.0 -2.79** 
Placebo 121 8.4 0.09 10.81, 22.52 91.0 -1.51 
Glimepiride 4 mg/day 242 8.4 -0.98 36.31, 56.02 89.0 0.95 
Add-on to glimepiride (4 mg/day) 
Liraglutide 1.2 mg 228 8.5 -1.08** 34.51, 57.42 80.0 0.32** 
Liraglutide 1.8 mg 234 8.5 -1.13** 41.61, 55.92 83.0 -0.23** 
Placebo 114 8.4 0.23 7.51, 11.82 81.9 -0.10 
Rosiglitazone 4 
mg/day 

231 8.4 -0.44 21.91, 36.12 80.6 2.11 

Add-on to metformin (2,000 mg/day) + rosiglitazone (4 mg twice daily) 
Liraglutide 1.2 mg 177 8.48 -1.48 57.51 95.3 -1.02 
Liraglutide 1.8 mg 178 8.56 -1.48 53.71 94.9 -2.02 
Placebo 175 8.42 -0.54 28.11 98.5 0.60 
Add-on to metformin (2,000 mg/day) + glimepiride (4 mg/day) 
Liraglutide 1.8 mg 230 8.3 -1.33* 53.11 85.8 -1.81** 
Placebo 114 8.3 -0.24 15.31 85.4 -0.42 
Insulin glargine4  232 8.1 -1.09 45.81 85.2 1.62 
Add-on to SGLT2i5 ± metformin (≥1500 mg/day) 
Liraglutide 1.8 mg 203 8.00 -1.02*** 54.8*** 91.0 -2.92 
Placebo 100 7.96 -0.28 13.9 91.4 -2.06 

*Superiority (p<0.01) vs active comparator; **Superiority (p<0.0001) vs active comparator; ***Superiority 
(p<0.001) vs active comparator, †Non-inferiority (p<0.0001) vs active comparator 
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 

Self-measured FPG Increase in insulin glargine dose (IU) 
≤5.5 mmol/l (≤100 mg/dl) Target No adjustment 
>5.5 and <6.7 mmol/l (>100 and <120 mg/dl) 0–2 IUa 
≥6.7 mmol/l (≥120 mg/dl) 2 IU 

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 



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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 [-1.00; -0.70]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. 



 12 

 
• 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). 
 

  

Pa
tie

nt
s w

ith
 a

n 
ev

en
t (

%
) 

Time from randomisation (months) 
Patients at risk 

FAS: full analysis set. 

Placebo 
Victoza 

HR: 0.87 
95% CI [0.78; 0.97] 

p<0.001 for non-inferiority 
p=0.005 for superiority 

Placebo 
Victoza 

4672 
4668 

4587 
4593 

4473 
4496 

4352 
4400 

4237 
4280 

4123 
4172 

4010 
4072 

3914 
3982 

1543 
1562 

407 
424 

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



 13 

    Hazard Ratio (95% CI) Victoza N (%) Placebo N (%) 

FAS: full analysis set 
CI: confidence interval  
MACE: major adverse cardiovascular event 
%: proportion in percent of subjects with an event 
N: number of subjects 

 

Favours Victoza Favours Placebo 
0.7 0.8 0.9 1.1 1.2 

Primary endpoint – MACE 

Components of MACE: 

 

FAS 

Cardiovascular death 

Non-fatal stroke 

Non-fatal myocardial infarction 

Expanded MACE 

Additional components in expanded MACE: 

Unstable angina pectoris (hospitalisation) 

Coronary revascularisation 

Heart failure (hospitalisation) 

Other secondary endpoints: 

All cause death 

Non-cardiovascular death 

1 

0.87 
(0.78-0.97) 

0.78  
(0.66-0.93) 

0.89  
(0.72-1.11) 

0.88 
(0.75-1.03) 

0.88  
(0.81-0.96) 

0.98 
(0.76-1.26) 

0.91 
(0.80-1.04) 

0.87 
(0.73-1.05) 

0.85 
(0.74-0.97) 

0.95 
(0.77-1.18) 

608 
(13.0) 

219 
(4.7) 
159  
(3.4) 
281  
(6.0) 
948  

(20.3) 

122 
(2.6) 
405 
(8.7) 
218 
(4.7) 

381 
(8.2) 
162 
(3.5) 

694 
(14.9) 

278  
(6.0) 
177  
(3.8) 
317  
(6.8) 
1062  
(22.7) 

124 
(2.7) 
441 
(9.4) 
248 
(5.3) 

447 
(9.6) 
169 
(3.6) 

4668 
(100) 4672 (100) 

 
Figure 2: Forest plot of analyses of individual cardiovascular event types – FAS population 
 
A significant and sustained reduction in HbA1c from baseline to month 36 was observed with 
liraglutide vs placebo, in addition to standard of care (-1.16% vs -0.77%; estimated treatment 
difference [ETD] -0.40% [-0.45; -0.34]). The need for treatment intensification with insulin was 
reduced by 48% with liraglutide vs placebo in insulin-naive patients at baseline (HR 0.52 [0.48; 
0.57]). 
 
• 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 [0.73, 0.97]. 
The HR for liraglutide vs placebo was 0.78 [0.67, 0.92] for time to first nephropathy event and 1.15 
[0.87, 1.52] 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, [-1.65, 0.46]). The 
treatment difference in HbA1c was 1.3% after additional 26 weeks of open label extension, confirming 
the sustained glycaemic control with Victoza. 
 



 14 

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%). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
The absorption of liraglutide following subcutaneous administration is slow, reaching maximum 
concentration 8–12 hours post dosing. Estimated maximum liraglutide concentration was 9.4 nmol/l 
(mean body weight approximately 73 kg) for a subcutaneous single dose of liraglutide 0.6 mg. At 
1.8 mg liraglutide, the average steady state concentration of liraglutide (AUCτ/24) reached 
approximately 34 nmol/l (mean body weight approximately 76 kg). The exposure of liraglutide 
decreases with increasing body weight. Liraglutide exposure increased proportionally with dose. The 
intra-subject coefficient of variation for liraglutide AUC was 11% following single dose 
administration. 
Absolute bioavailability of liraglutide following subcutaneous administration is approximately 55%. 
 
Distribution 



 15 

 
The apparent volume of distribution after subcutaneous administration is 11–17 l. The mean volume of 
distribution after intravenous administration of liraglutide is 0.07 l/kg. Liraglutide is extensively bound 
to plasma proteins (>98%). 
 
Biotransformation 
 
During 24 hours following administration of a single radiolabelled [3H]-liraglutide dose to healthy 
subjects, the major component in plasma was intact liraglutide. Two minor plasma metabolites were 
detected (≤9% and ≤5% of total plasma radioactivity exposure). Liraglutide is metabolised in a similar 
manner to large proteins without a specific organ having been identified as major route of elimination. 
 
Elimination 
 
Following a [3H]-liraglutide dose, intact liraglutide was not detected in urine or faeces. Only a minor 
part of the administered radioactivity was excreted as liraglutide-related metabolites in urine or faeces 
(6% and 5%, respectively). The urine and faeces radioactivity was mainly excreted during the first 6–
8 days, and corresponded to three minor metabolites, respectively. 
 
The mean clearance following subcutaneous administration of a single dose liraglutide is 
approximately 1.2 l/h with an elimination half-life of approximately 13 hours. 
 
Special populations 
 
Elderly patients 
Age had no clinically relevant effect on the pharmacokinetics of liraglutide based on the results from a 
pharmacokinetic study in healthy subjects and population pharmacokinetic data analysis of patients 
(18 to 80 years). 
 
Gender 
Gender had no clinically meaningful effect on the pharmacokinetics of liraglutide based on the results 
of population pharmacokinetic data analysis of male and female patients and a pharmacokinetic study 
in healthy subjects. 
 
Ethnic origin 
Ethnic origin had no clinically relevant effect on the pharmacokinetics of liraglutide based on the 
results of population pharmacokinetic analysis which included patients of White, Black, Asian and 
Hispanic groups. 
 
Obesity 
Population pharmacokinetic analysis suggests that body mass index (BMI) has no significant effect on 
the pharmacokinetics of liraglutide. 
 
Hepatic impairment 
The pharmacokinetics of liraglutide was evaluated in patients with varying degree of hepatic 
impairment in a single-dose trial. Liraglutide exposure was decreased by 13–23% in patients with mild 
to moderate hepatic impairment compared to healthy subjects. 
Exposure was significantly lower (44%) in patients with severe hepatic impairment (Child Pugh 
score >9). 
 
Renal impairment 
Liraglutide exposure was reduced in patients with renal impairment compared to individuals with 
normal renal function. Liraglutide exposure was lowered by 33%, 14%, 27% and 26% in patients with 
mild (creatinine clearance, CrCl 50–80 ml/min), moderate (CrCl 30–50 ml/min), and severe (CrCl 
<30 ml/min) renal impairment and in end-stage renal disease requiring dialysis, respectively. 
 
Similarly, in a 26-week clinical trial, patients with type 2 diabetes and moderate renal impairment 



 16 

(CrCL 30–59 ml/min, see section 5.1) had 26% lower liraglutide exposure when compared with a 
separate trial including patients with type 2 diabetes with normal renal function or mild renal 
impairment.  
 
Paediatric population 
Pharmacokinetic properties were assessed in clinical studies in the paediatric population with type 2 
diabetes aged 10 years and above. The liraglutide exposure in adolescents and children was 
comparable to that observed in the adult population. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazards for humans based on conventional studies of safety 
pharmacology, repeat-dose toxicity or genotoxicity. 
 
Non-lethal thyroid C-cell tumours were seen in 2-year carcinogenicity studies in rats and mice. In rats, 
a no observed adverse effect level (NOAEL) was not observed. These tumours were not seen in 
monkeys treated for 20 months. These findings in rodents are caused by a non-genotoxic, specific 
GLP-1 receptor-mediated mechanism to which rodents are particularly sensitive. The relevance for 
humans is likely to be low but cannot be completely excluded. No other treatment-related tumours 
have been found. 
 
Animal studies did not indicate direct harmful effects with respect to fertility but slightly increased 
early embryonic deaths at the highest dose. Dosing with Victoza during mid-gestation caused a 
reduction in maternal weight and foetal growth with equivocal effects on ribs in rats and skeletal 
variation in the rabbit. Neonatal growth was reduced in rats while exposed to Victoza, and persisted in 
the post-weaning period in the high dose group. It is unknown whether the reduced pup growth is 
caused by reduced pup milk intake due to a direct GLP-1 effect or reduced maternal milk production 
due to decreased caloric intake. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Disodium phosphate dihydrate 
Propylene glycol 
Phenol 
Water for injections 
 
6.2 Incompatibilities 
 
Substances added to Victoza may cause degradation of liraglutide. In the absence of compatibility 
studies, this medicinal product must not be mixed with other medicinal products. 
 
6.3 Shelf life 
 
30 months. 
 
After first use: 1 month. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C–8°C). 
Do not freeze. 
Store away from the freezer compartment. 
 
After first use: Store below 30°C or store in a refrigerator (2°C–8°C). Do not freeze. 



 17 

 
Keep the cap on the pen in order to protect from light. 
 
6.5 Nature and contents of container 
 
Cartridge (type 1 glass) with a plunger (bromobutyl) and a laminate rubber sheet 
(bromobutyl/polyisoprene) contained in a pre-filled multidose disposable pen made of polyolefin and 
polyacetal. 
 
Each pen contains 3 ml solution, delivering 30 doses of 0.6 mg, 15 doses of 1.2 mg or 10 doses of 
1.8 mg. 
 
Pack sizes of 1, 2, 3, 5 or 10 pre-filled pens. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Victoza should not be used if it does not appear clear and colourless or almost colourless. 
Victoza should not be used if it has been frozen. 
 
Victoza can be administered with needles up to a length of 8 mm and as thin as 32G. The pen is 
designed to be used with NovoFine or NovoTwist disposable needles. 
Needles are not included. 
The patient should be advised to discard the injection needle in accordance with local requirements 
after each injection and store the pen without an injection needle attached. This prevents 
contamination, infection and leakage. It also ensures that the dosing is accurate. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/09/529/001-005 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 30 June 2009 
Date of last renewal: 11 April 2014 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

  

http://www.ema.europa.eu/


 18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR 
BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 

SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 



 19 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
Novo Nordisk A/S 
Hallas Allé 
DK-4400 Kalundborg 
Denmark 
 
Name and address of the manufacturer responsible for batch release 
 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed Risk Management Plan (RMP) presented in Module 1.8.2 of the Marketing Authorisation and 
any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
  



 20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 
 
  



 21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 
 

  



 22 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Victoza 6 mg/ml solution for injection in pre-filled pen 
Liraglutide 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
1 ml contains 6 mg of liraglutide. One pre-filled pen contains 18 mg liraglutide 
 
 
3. LIST OF EXCIPIENTS 
 
Disodium phosphate dihydrate, propylene glycol, phenol, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection. 
 
1 pen 
2 pens 
3 pens 
5 pens 
10 pens 
 
Each pen contains 3 ml solution, delivering 30 doses of 0.6 mg, 15 doses of 1.2 mg or 10 doses of 
1.8 mg. 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous use 
 
Victoza pen is designed to be used with NovoFine or NovoTwist disposable needles. 
Needles are not included. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNINGS, IF NECESSARY 
 
Do not store the pen with a needle attached. 
For use by one person only  
 



 23 

 
8. EXPIRY DATE 
 
EXP 
 
Discard pen 1 month after first use. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
After first use of the pen, store below 30°C or in a refrigerator. Do not freeze. 
Keep the pen cap on in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
 
12. MARKETING AUTHORISATION NUMBERS 
 
EU/1/09/529/001   1 x 3 ml 
EU/1/09/529/002   2 x 3 ml 
EU/1/09/529/003   3 x 3 ml 
EU/1/09/529/004   5 x 3 ml 
EU/1/09/529/005   10 x 3 ml 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Victoza 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 



 24 

2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



 25 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED PEN LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Victoza 6 mg/ml injection 
Liraglutide 
Subcutaneous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Batch 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3 ml 
 
 
6. OTHER 
 
Novo Nordisk A/S 

  



 26 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 
 



 27 

Package leaflet: Information for the user 
 

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

 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
– Keep this leaflet. You may need to read it again. 
– If you have any further questions, ask your doctor, pharmacist or nurse. 
– This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
– If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Victoza is and what it is used for 
2. What you need to know before you use Victoza 
3. How to use Victoza 
4. Possible side effects 
5. How to store Victoza 
6. Contents of the pack and other information 
 
 
1. What Victoza is and what it is used for 
 
Victoza contains the active substance liraglutide. It helps your body reduce your blood sugar level 
only when blood sugar is too high. It also slows food passage through your stomach and can help 
prevent heart disease. 
 
Victoza is used on its own if your blood sugar is not properly controlled by diet and exercise alone, 
and you cannot use metformin (another diabetes medicine). 
 
Victoza is used with other medicines for diabetes when they are not enough to control your blood 
sugar levels. These may include: 
• oral antidiabetics (such as metformin, pioglitazone, sulfonylurea, sodium-glucose cotransporter 

2 inhibitor (SGLT2i)) and/or insulin. 
 
 
2. What you need to know before you use Victoza 
 
Do not use Victoza 
– if you are allergic to liraglutide or any of the other ingredients of this medicine (listed in section 

6). 
 
Warnings and precautions 
Talk to your doctor, pharmacist or nurse: 
• before using Victoza. 
• if you have or have had a disease of the pancreas. 
 
This medicine should not be used if you have type 1 diabetes (your body does not produce any insulin) 
or diabetic ketoacidosis (a complication of diabetes with high blood sugar and increase in effort to 
breathe). It is not an insulin and should therefore not be used as a substitute for insulin. 
 
The use of Victoza is not recommended if you are on dialysis. 
The use of Victoza is not recommended if you have severe liver disease. 
The use of Victoza is not recommended if you have severe heart failure. 



 28 

 
This medicine is not recommended if you have a severe stomach or gut problem which results in 
delayed stomach emptying (called gastroparesis), or inflammatory bowel disease. 
 
If you have symptoms of acute pancreatitis, such as persistent, severe stomach ache, you should 
consult your doctor immediately (see section 4). 
 
If you have thyroid disease including thyroid nodules and enlargement of the thyroid gland, consult 
your doctor. 
 
When initiating treatment with Victoza, you may in some cases experience loss of fluids/dehydration, 
e.g. in case of vomiting, nausea and diarrhoea. It is important to avoid dehydration by drinking plenty 
of fluids. Contact your doctor if you have any questions or concerns. 
 
Children and adolescents 
Victoza can be used in adolescents and children aged 10 years and above. No data are available in 
children below 10 years of age. 
 
Other medicines and Victoza 
Please tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any 
other medicines. 
 
In particular, tell your doctor, pharmacist or nurse if you are using medicines containing any of the 
following active substances: 
• Sulfonylurea (such as glimepiride or glibenclamide) or insulin. You may get hypoglycaemia 

(low blood sugar) when using Victoza together with a sulfonylurea or insulin, as sulfonylureas 
and insulin increase the risk of hypoglycaemia. When you first start using these medicines 
together, your doctor may tell you to lower the dose of the sulfonylurea or insulin. Please see 
section 4 for the warning signs of low blood sugar. If you are also taking a sulfonylurea (such as 
glimepiride or glibenclamide) or insulin, your doctor may tell you to test your blood sugar 
levels. This will help your doctor to decide if the dose of the sulfonylurea or insulin needs to be 
changed. 

• If you are using insulin, your doctor will tell you how to reduce the dose of insulin and will 
recommend you to monitor your blood sugar more frequently, in order to avoid hyperglycaemia 
(high blood sugar) and diabetic ketoacidosis (a complication of diabetes that occurs when the 
body is unable to break down glucose because there is not enough insulin). 

• Warfarin or other oral anti-coagulation medicines. More frequent blood testing to determine the 
ability of your blood to clot may be required. 

 
Pregnancy and breast-feeding 
Tell your doctor if you are, you think you might be, or are planning to become pregnant. Victoza 
should not be used during pregnancy because it is not known if it may harm your unborn child. 
 
It is not known if Victoza passes into breast milk, therefore do not use this medicine if you are breast-
feeding. 
 
Driving and using machines 
Low blood sugar (hypoglycaemia) may reduce your ability to concentrate. Avoid driving or using 
machines if you experience signs of hypoglycaemia. Please see section 4 for the warning signs of low 
blood sugar. Please consult your doctor for further information on this topic. 
 
Important information about some of the ingredients of Victoza 
This medicine contains less than 1 mmol sodium (23 mg) per dose. This means that it is essentially 
‘sodium free’. 
 
 
3. How to use Victoza 



 29 

 
Always use this medicine exactly as your doctor has told you. Check with your doctor, pharmacist or 
nurse if you are not sure. 
 
• The starting dose is 0.6 mg once a day, for at least one week. 
• Your doctor will tell you when to increase it to 1.2 mg once a day. 
• Your doctor may tell you to further increase the dose to 1.8 mg once a day, if your blood 

glucose is not adequately controlled with a dose of 1.2 mg. 
Do not change your dose unless your doctor has told you to. 
 
Victoza is given as an injection under the skin (subcutaneous). Do not inject it into a vein or muscle. 
The best places to give yourself the injection are the front of your thighs, the front of your waist 
(abdomen), or your upper arm. 
 
You can give yourself the injection at any time of the day, regardless of meals. When you have found 
the most convenient time of the day it is preferred that you inject Victoza around the same time of the 
day. 
 
Before you use the pen for the first time, your doctor or nurse will show you how to use it. 
Detailed instructions for use are provided on the other side of this leaflet. 
 
If you use more Victoza than you should 
If you use more Victoza than you should, talk to your doctor straight away. You may need medical 
treatment. You may experience nausea, vomiting or diarrhoea. 
 
If you forget to use Victoza 
If you forget a dose, use Victoza as soon as you remember. 
However, if it is more than 12 hours since you should have used Victoza, skip the missed dose. Then 
take your next dose as usual the following day. 
Do not take an extra dose or increase the dose on the following day to make up for the missed dose. 
 
If you stop using Victoza 
Do not stop using Victoza without talking to your doctor. If you stop using it, your blood sugar levels 
may increase. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Serious side effects 
Common: may affect up to 1 in 10 people 
• Hypoglycaemia (low blood sugar). The warning signs of low blood sugar may come on 

suddenly and can include: cold sweat, cool pale skin, headache, fast heartbeat, feeling sick, 
feeling very hungry, changes in vision, feeling sleepy, feeling weak, nervous, anxious, 
confused, difficulty concentrating, shaking (tremor). Your doctor will tell you how to treat low 
blood sugar and what to do if you notice these warning signs. This is more likely to happen if 
you also take a sulfonylurea or insulin. Your doctor may reduce your dose of these medicines 
before you start using Victoza. 

 
Rare: may affect up to 1 in 1,000 people 
• A severe form of allergic reaction (anaphylactic reaction) with additional symptoms such as 

breathing problems, swelling of throat and face, fast heartbeat, etc. If you experience these 
symptoms you should seek immediate medical help and inform your doctor as soon as possible. 



 30 

• Bowel obstruction. A severe form of constipation with additional symptoms such as stomach 
ache, bloating, vomiting etc. 

 
Very rare: may affect up to 1 in 10,000 people 
• Cases of inflammation of the pancreas (pancreatitis). Pancreatitis can be a serious, potentially 

life-threatening medical condition. Stop taking Victoza and contact a doctor immediately if you 
notice any of the following serious side effects: 

 
 Severe and persistent pain in the abdomen (stomach area) which might reach through to your 

back, as well as nausea and vomiting, as it could be a sign of an inflamed pancreas 
(pancreatitis). 

 
Other side effects 
Very common: may affect more than 1 in 10 people 
• Nausea (feeling sick). This usually goes away over time. 
• Diarrhoea. This usually goes away over time. 
 
Common 
• Vomiting. 
 
When initiating treatment with Victoza, you may in some cases experience loss of fluids/dehydration, 
e.g. in case of vomiting, nausea and diarrhoea. It is important to avoid dehydration by drinking plenty 
of fluids. 
 
• Headache 
• Indigestion 
• Inflamed stomach (gastritis). The signs include stomach ache, nausea and vomiting. 
• Gastro-oesophageal reflux disease (GORD). The signs include heartburn. 
• Painful or swollen tummy (abdomen) 
• Abdominal discomfort 
• Constipation 
• Wind (flatulence) 
• Decreased appetite 
• Bronchitis 
• Common cold 
• Dizziness 
• Increased pulse 
• Tiredness 
• Toothache 
• Injection site reactions (such as bruising, pain, irritation, itching and rash) 
• Increase of pancreatic enzymes (such as lipase and amylase). 
 
Uncommon: may affect up to 1 in 100 people 
• Allergic reactions like pruritus (itching) and urticaria (a type of skin rash) 
• Dehydration, sometimes with a decrease in kidney function 
• Malaise (feeling unwell) 
• Gallstones 
• Inflamed gallbladder 
• A delay in the emptying of the stomach. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 31 

5. How to store Victoza 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the pen label and carton after ‘EXP’. 
The expiry date refers to the last day of that month. 
 
Before opening: 
Store in a refrigerator (2˚C–8˚C). Do not freeze. Keep away from the freezer compartment. 
 
During use: 
You can keep the pen for 1 month when stored at a temperature below 30˚C or in a refrigerator (2˚C–
8˚C), away from the freezer compartment. Do not freeze. 
When you are not using the pen, keep the pen cap on in order to protect from light. 
 
Do not use this medicine if the solution is not clear and colourless or almost colourless. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Victoza contains 
– The active substance is liraglutide. 1 ml solution for injection contains 6 mg liraglutide. One 

pre-filled pen contains 18 mg liraglutide. 
– The other ingredients are disodium phosphate dihydrate, propylene glycol, phenol and water for 

injections. 
 
What Victoza looks like and contents of the pack 
Victoza is supplied as a clear, and colourless or almost colourless, solution for injection in a pre-filled 
pen. Each pen contains 3 ml of solution, delivering 30 doses of 0.6 mg, 15 doses of 1.2 mg or 10 doses 
of 1.8 mg. 
 
Victoza is available in packs containing 1, 2, 3, 5 or 10 pens. Not all pack sizes may be marketed. 
Needles are not included. 
 
Marketing Authorisation Holder and Manufacturer 
 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
This leaflet was last revised in  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu 
  

http://www.ema.europa.eu/


 32 

INSTRUCTIONS FOR USING THE VICTOZA PEN 
Please read these instructions carefully before using 
your pen. 
Your pen comes with 18 mg of liraglutide. You can select 
doses of 0.6 mg, 1.2 mg and 1.8 mg. 
The pen is designed to be used with NovoFine or 
NovoTwist disposable injection needles up to a length of 
8 mm and as thin as 32G (0.25/0.23 mm).  

 

Prepare your pen 
 
Check the name and coloured label of your pen to make 
sure that it contains liraglutide. Using the wrong medicine 
could cause severe harm. 
 
Pull off the pen cap. 

 

Pull off the paper tab from a new disposable needle. 
Screw the needle straight and tightly onto your pen. 

 

Pull off the outer needle cap and keep it for later. 

 

Pull off the inner needle cap and dispose of it. 

 

 Always use a new needle for each injection. This reduces the risk of contamination, infection, 
leakage of liraglutide, blocked needles and inaccurate dosing. 

 Be careful not to bend or damage the needle. 
 Never try to put the inner needle cap back on the needle. You may stick yourself with the 

needle. 

Caring for your pen 
• Do not try to repair your pen or pull it apart. 
• Keep your pen away from dust, dirt and all kinds of liquids. 
• Clean the pen with a cloth moistened with a mild detergent. 



 33 

• Do not try to wash, soak or lubricate it – this can harm the pen. 

 Important information 
• Do not share your pen or needles with anyone else. 
• Keep your pen out of the reach of others, especially children. 

With each new pen, check the flow 
 
Check the flow before your first injection with each 
new pen. If your pen is already in use, go to ‘Select 
your dose’, step H. 
 
Turn the dose selector until the flow check symbol lines 
up with the pointer. 

 

Hold the pen with the needle pointing up. Tap the 
cartridge gently with your finger a few times. This will 
make any air bubbles collect at the top of the cartridge. 

 

Keep the needle pointing up and press the dose button 
until 0 mg lines up with the pointer. 
 
A drop of liraglutide should appear at the needle tip. If no 
drop appears, repeat steps E to G up to four times. 
 
If there is still no drop of liraglutide, change the needle 
and repeat steps E to G once more. 
 
Do not use the pen if a drop of liraglutide still does not 
appear. This indicates the pen is defective and you must 
use a new one.  

 If you have dropped your pen against a hard surface or suspect that something is wrong with it, 
always put on a new disposable needle and check the flow before you inject. 



 34 

Select your dose 
 
Always check that the pointer lines up with 0 mg. 
 
Turn the dose selector until your needed dose lines up 
with the pointer (0.6 mg, 1.2 mg or 1.8 mg). 
 
If you selected a wrong dose by mistake, simply change it 
by turning the dose selector backwards or forwards until 
the right dose lines up with the pointer. 
 
Be careful not to press the dose button when turning the 
dose selector backwards, as liraglutide may come out. 
 
If the dose selector stops before your needed dose lines up 
with the pointer, there is not enough liraglutide left for a 
full dose. Then you can either: 
 
Split your dose into two injections: 
Turn the dose selector in either direction until 0.6 mg or 
1.2 mg lines up with the pointer. Inject the dose. Then 
prepare a new pen for injection and inject the remaining 
number of mg to complete your dose. 
 
You may only split your dose between your current pen 
and a new pen if trained or advised by your healthcare 
professional. Use a calculator to plan the doses. If you 
split the dose wrong, you may inject too much or too little 
liraglutide. 
 
Inject the full dose with a new pen: 
If the dose selector stops before 0.6 mg lines up with the 
pointer, prepare a new pen and inject the full dose with 
the new pen. 

 

 Do not try to select other doses than 0.6 mg, 1.2 mg or 1.8 mg. The numbers in the display 
must line up precisely with the pointer to ensure that you get the correct dose. 
The dose selector clicks when you turn it. Do not use these clicks to select your dose. 
Do not use the cartridge scale to measure how much liraglutide to inject – it is not accurate 
enough. 

Inject your dose 
 
Insert the needle into your skin using the injection 
technique shown by your doctor or nurse. Then follow 
the instructions below: 
 
Press the dose button to inject until 0 mg lines up with the 
pointer. Be careful not to touch the display with your 
other fingers or press the dose selector sideways when 
you inject. This is because it may block the injection. 
Keep the dose button pressed down and leave the needle 
under the skin for at least 6 seconds. This is to make sure 
that you get your full dose.  

 



 35 

Pull out the needle. 
After that, you may see a drop liraglutide at the needle 
tip. 
This is normal and does not affect your dose. 

 

Guide the needle tip into the outer needle cap without 
touching the needle or the outer needle cap. 

 

When the needle is covered, carefully push the outer 
needle cap completely on. Then unscrew the needle. 
Dispose of it carefully and put the pen cap back on. 
 
When the pen is empty, carefully dispose of it without a 
needle attached. Please dispose of the pen and needle in 
accordance with local requirements. 

 

 Always remove the needle after each injection, and store your pen without a needle attached. 
 This reduces the risk of contamination, infection, leakage of liraglutide, blocked needles and 

inaccurate dosing. 
 Caregivers must be very careful when handling used needles – to prevent needle injury and 

cross-infection. 

 
  



 36 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Annex IV 
 

Scientific conclusions and grounds for the variation to the terms of the marketing 
authorisation 

 
 
 
  



 37 

Scientific conclusions 
 
Taking into account the PRAC Assessment Report on the PSUR for liraglutide, the scientific 
conclusions of CHMP are as follows:  
 
Data from clinical trials showed that liraglutide is associated with delayed gastric emptying. In the 
LEADER study, delayed gastric emptying was reported three times more frequently in the liraglutide 
group compared to the placebo group. As there is sufficient evidence to conclude on a causal 
relationship between delayed gastric emptying and liraglutide, delayed gastric emptying should be 
included as an ADR in section 4.8 of the SmPC with a frequency allocation of ‘uncommon’ and in 
section 4 of the Package Leaflet. 
 
The CHMP agrees with the scientific conclusions made by the PRAC. 
 
Grounds for the variation to the terms of the marketing authorisation 
 
On the basis of the scientific conclusions for liraglutide the CHMP is of the opinion that the benefit-
risk balance of the medicinal product(s) containing liraglutide is unchanged subject to the proposed 
changes to the product information 
 
The CHMP recommends that the terms of the marketing authorisation should be varied. 
 
 


	ANNEX ISUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
	Scientific conclusions and grounds for the variation to the terms of the marketing authorisation