SAXENDA 6mg / ml solution for injection in pre-filled pen medication leaflet

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

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.

Solution for injection.

Clear and colourless or almost colourless, isotonic solution; pH=8.15.

Saxenda is indicated as an adjunct to a reduced-calorie diet and increased physical activity for weightmanagement in adult patients with an initial Body Mass Index (BMI) of:

* ≥ 30 kg/m² (obesity), or

* ≥ 27 kg/m² to <30 kg/m² (overweight) in the presence of at least one weight-related comorbiditysuch as dysglycaemia (prediabetes or type 2 diabetes mellitus), hypertension, dyslipidaemia orobstructive sleep apnoea.

Treatment with Saxenda should be discontinued after 12 weeks on the 3.0 mg/day dose if patientshave not lost at least 5% of their initial body weight.

Adolescents (≥ 12 years)

Saxenda can be used as an adjunct to a healthy nutrition and increased physical activity for weightmanagement in adolescent patients from the age of 12 years and above with:

* obesity (BMI corresponding to ≥ 30 kg/m2 for adults by international cut-off points)* and

* body weight above 60 kg.

Treatment with Saxenda should be discontinued and re-evaluated if patients have not lost at least 4%of their BMI or BMI z score after 12 weeks on the 3.0 mg/day or maximum tolerated dose.

*IOTF BMI cut-off points for obesity by sex between 12-18 years (see table 1), in accordance withstudy design of the Trial 4180, see section 5.1.

Table 1 IOTF BMI cut-off points for obesity by sex between 12-18 years

Age BMI corresponding to 30 kg/m2 for adults by international(years) cut-off points.

Males Females12 26.02 26.6712.5 26.43 27.2413 26.84 27.7613.5 27.25 28.2014 27.63 28.5714.5 27.98 28.8715 28.30 29.1115.5 28.60 29.2916 28.88 29.4316.5 29.14 29.5617 29.41 29.6917.5 29.70 29.8418 30.00 30.00

Children (6 to <12 years)

Saxenda is indicated as an adjunct to healthy nutrition and increased physical activity for weightmanagement in children from the age of 6 to <12 years with

* obesity (BMI ≥95th percentile)* and

* body weight ≥45 kg

Treatment with Saxenda should be discontinued and re-evaluated if patients have not lost at least 4%of their BMI or BMI z score after 12 weeks on the 3.0 mg/day or maximum tolerated dose.

*CDC BMI cut-off points for obesity (≥95th percentile) by sex between 6 to <12 years (see table 2), inaccordance with study design of the Trial 4392, see section 5.1.

Table 2 Cut-off points for BMI (Weight in kg/Height in m2) for obesity (≥95th percentile) by sexfor children from 6 and < 12 years of age

Obesity

Age (Years) BMI ≥ 95th percentile

Males Females6 18.41 18.846.5 18.76 19.237 19.15 19.687.5 19.59 20.178 20.07 20.708.5 20.57 21.259 21.09 21.829.5 21.62 22.4010 22.15 22.9810.5 22.69 23.5711 23.21 24.14

Obesity

Age (Years) BMI ≥ 95th percentile

Males Females11.5 23.73 24.71

The starting dose is 0.6 mg once daily. The dose should be increased to 3.0 mg once daily inincrements of 0.6 mg with at least one-week intervals to improve gastro-intestinal tolerability (seetable 3). If escalation to the next dose step is not tolerated for two consecutive weeks, considerdiscontinuing treatment. Daily doses higher than 3.0 mg are not recommended.

Table 3 Dose escalation schedule

Dose Weeks0.6 mg 1

Dose escalation 1.2 mg 14 weeks 1.8 mg 12.4 mg 1

Maintenance dose 3.0 mg

Adolescents (≥ 12 years)

For adolescents from the age of 12 to below 18 years old a similar dose escalation schedule as foradults should be applied (see table 3). The dose should be increased until 3.0 mg (maintenance dose)or maximum tolerated dose has been reached. Daily doses higher than 3.0 mg are not recommended.

Children (6 to <12 years)

For children from the age of 6 to below 12 years old a similar dose escalation schedule as for adultsshould be applied (see table 3). The dose should be increased until 3.0 mg (maintenance dose) ormaximum tolerated dose has been reached. Daily doses higher than 3.0 mg are not recommended.

Liraglutide in children should be initiated by a physician experienced in the management of obesity inchildren.

If a dose is missed within 12 hours from when it is usually taken, the patient should take the dose assoon as possible. If there is less than 12 hours to the next dose, the patient should not take the misseddose and resume the once-daily regimen with the next scheduled dose. An extra dose or increase indose should not be taken to make up for the missed dose.

Saxenda should not be used in combination with another GLP-1 receptor agonist.

When initiating Saxenda, it should be considered to reduce the dose of concomitantly administeredinsulin or insulin secretagogues (such as sulfonylureas) to reduce the risk of hypoglycaemia. Bloodglucose self-monitoring is necessary to adjust the dose of insulin or insulin-secretagogues (see section4.4).

Elderly (≥ 65 years old)

No dose adjustment is required based on age. Therapeutic experience in patients ≥ 75 years of age islimited and use in these patients is not recommended (see sections 4.4 and 5.2).

No dose adjustment is required for patients with mild or moderate renal impairment (creatinineclearance ≥ 30 ml/min). Saxenda is not recommended for use in patients with severe renal impairment(creatinine clearance < 30 ml/min) including patients with end-stage renal disease (see sections 4.4,4.8 and 5.2).

No dose adjustment is recommended for patients with mild or moderate hepatic impairment. Saxendais not recommended for use in patients with severe hepatic impairment and should be used cautiouslyin patients with mild or moderate hepatic impairment (see sections 4.4 and 5.2).

No dose adjustment is required for adolescents and children from the age of 6 years and above.

The safety and efficacy of Saxenda in children below 6 years of age has not been established (seesection 5.1).

Saxenda is for subcutaneous use only. It must not be administered intravenously or intramuscularly.

Saxenda is administered once daily at any time, independent of meals. It should be injected in theabdomen, thigh or upper arm. The injection site and timing can be changed without dose adjustment.

However, it is preferable that Saxenda is injected around the same time of the day, when the mostconvenient time of the day has been chosen. Injection sites should always be rotated to reduce the riskof injection site amyloid deposits (see section and 4.8).

For further instructions on administration, see section 6.6.

Hypersensitivity to liraglutide or to any of the excipients listed in section 6.1.

Aspiration in association with general anaesthesia or deep sedation

Cases of pulmonary aspiration have been reported in patients receiving GLP-1 receptor agonistsundergoing general anaesthesia or deep sedation. Therefore, the increased risk of residual gastriccontent due to delayed gastric emptying (see section 4.8) should be considered prior to performingprocedures with general anaesthesia or deep sedation.

In order to improve the traceability of biological medicinal products, the name and the batch numberof the administered product should be clearly recorded.

There is no clinical 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.

The safety and efficacy of liraglutide for weight management have not been established in patients:- aged 75 years or more,- treated with other products for weight management,- with obesity secondary to endocrinological or eating disorders or to treatment with medicinalproducts that may cause weight gain,- with severe renal impairment,- with severe hepatic impairment.

Use in these patients is not recommended (see section 4.2).

As liraglutide for weight management was not investigated in subjects with mild or moderate hepaticimpairment, it should be used with caution in these patients (see sections 4.2 and 5.2).

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 transientgastrointestinal adverse reactions, including nausea, vomiting and diarrhoea.

Acute pancreatitis has been observed with the use of GLP-1 receptor agonists. Patients should beinformed of the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, liraglutideshould be discontinued; if acute pancreatitis is confirmed, liraglutide should not be restarted.

In clinical trials for weight management, a higher rate of cholelithiasis and cholecystitis was observedin patients treated with liraglutide than in patients on placebo. The fact that substantial weight loss canincrease the risk of cholelithiasis and thereby cholecystitis only partially explained the higher rate withliraglutide. Cholelithiasis and cholecystitis may lead to hospitalisation and cholecystectomy. Patientsshould be informed of the characteristic symptoms of cholelithiasis and cholecystitis.

In clinical trials in type 2 diabetes, thyroid adverse events, such as goitre, have been reported inparticular in patients with pre-existing thyroid disease. Liraglutide should therefore be used withcaution in patients with thyroid disease.

An increase in heart rate was observed with liraglutide in clinical trials (see section 5.1). Heart rateshould be monitored at regular intervals consistent with usual clinical practice. Patients should beinformed of the symptoms of increased heart rate (palpitations or feelings of a racing heartbeat whileat rest). For patients who experience a clinically relevant sustained increase in resting heart rate,treatment with liraglutide should be discontinued.

Signs and symptoms of dehydration, including renal impairment and acute renal failure, have beenreported in patients treated with GLP-1 receptor agonists. Patients treated with liraglutide should beadvised of the potential risk of dehydration in relation to gastrointestinal side effects and takeprecautions to avoid fluid depletion.

Patients with type 2 diabetes mellitus receiving liraglutide in combination with insulin and/orsulfonylurea may have an increased risk of hypoglycaemia. The risk of hypoglycaemia may belowered by a reduction in the dose of insulin and/or sulfonylurea.

Episodes of clinically significant hypoglycaemia have been reported in adolescents (≥ 12 years)treated with liraglutide. Patients should be informed about the characteristic symptoms ofhypoglycaemia and the appropriate actions.

In patients with diabetes mellitus Saxenda must not be used as a substitute for insulin. Diabeticketoacidosis has been reported in insulin-dependent patients after rapid discontinuation or dosereduction of insulin (see section 4.2).

Saxenda contains less than 1 mmol sodium (23 mg) per dose, therefore the medicinal product isessentially ‘sodium-free’.

In vitro, liraglutide has shown very low potential to be involved in pharmacokinetic interactions withother active substances related to cytochrome P450 (CYP) and plasma protein binding.

The small delay of gastric emptying with liraglutide may influence absorption of concomitantlyadministered oral medicinal products. Interaction studies did not show any clinically relevant delay ofabsorption and therefore no dose adjustment is required.

Interaction studies have been performed with 1.8 mg liraglutide. The effect on rate of gastric emptyingwas equivalent between liraglutide 1.8 mg and 3.0 mg, (paracetamol AUC0-300 min). Few patientstreated with liraglutide reported at least one episode of severe diarrhoea. Diarrhoea may affect theabsorption of concomitant oral medicinal products.

No interaction study has been performed. A clinically relevant interaction with active substances withpoor solubility or narrow therapeutic index such as warfarin cannot be excluded. Upon initiation ofliraglutide treatment in patients on warfarin or other coumarin derivatives, more frequent monitoringof International Normalised Ratio (INR) is recommended.

Liraglutide did not change the overall exposure of paracetamol following a single dose of 1 000 mg.

Paracetamol Cmax was decreased by 31% and median tmax was delayed up to 15 min. No doseadjustment for concomitant use of paracetamol is required.

Liraglutide did not change the overall exposure of atorvastatin following single dose administration ofatorvastatin 40 mg. Therefore, no dose adjustment of atorvastatin is required when given withliraglutide. Atorvastatin Cmax was decreased by 38% and median tmax was delayed from 1 h to 3 h withliraglutide.

Liraglutide did not change the overall exposure of griseofulvin following administration of a singledose 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 arenot required.

A single dose administration of digoxin 1 mg with liraglutide resulted in a reduction of digoxin AUCby 16%; Cmax decreased by 31%. Digoxin median tmax was delayed from 1 h to 1.5 h. No doseadjustment of digoxin is required based on these results.

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 withliraglutide. No dose adjustment of lisinopril is required based on these results.

Liraglutide lowered ethinylestradiol and levonorgestrel Cmax by 12% and 13%, respectively, followingadministration of a single dose of an oral contraceptive product. tmax was delayed by 1.5 h withliraglutide for both compounds. There was no clinically relevant effect on the overall exposure ofeither ethinylestradiol or levonorgestrel. The contraceptive effect is therefore anticipated to beunaffected when co-administered with liraglutide.

Interaction studies have only been performed in adults.

There are limited data from the use of liraglutide in pregnant women. Studies in animals have shownreproductive toxicity (see section 5.3). The potential risk for humans is unknown.

Liraglutide should not be used during pregnancy. If a patient wishes to become pregnant or pregnancyoccurs, treatment with liraglutide should be discontinued.

It is not known whether liraglutide is excreted in human milk. Animal studies have shown that thetransfer of liraglutide and metabolites of close structural relationship into milk is low. Non-clinicalstudies have shown a treatment-related reduction of neonatal growth in suckling rat pups (see section5.3). Because of lack of experience, Saxenda should not be used during breast-feeding.

Apart from a slight decrease in the number of live implants, animal studies did not indicate harmfuleffects with respect to fertility (see section 5.3).

Saxenda has no or negligible influence on the ability to drive and use machines. However, dizzinesscan be experienced mainly during the first 3 months of treatment with Saxenda. Driving or use ofmachines should be exercised with caution if dizziness occurs.

Saxenda was evaluated for safety in 5 double-blind, placebo-controlled trials that enrolled 5 813 adultpatients with overweight or obesity with at least one weight-related comorbidity. Overall,gastrointestinal reactions were the most frequently reported adverse reactions during treatment(67.9%) (see section ‘Description of selected adverse reactions’).

Table 4 lists adverse reactions reported in adults. Adverse reactions are listed by system organ classand frequency. Frequency categories 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). andnot known (cannot be estimated from the available data). Within each frequency grouping, adversereactions are presented in order of decreasing seriousness.

Table 4 Adverse reactions reported in adults

MedDRA system Very common Common Uncommon Rare Not knownorgan classes

Immune system Anaphylacticdisorders reaction

Metabolism and Hypoglycaemia* Dehydrationnutrition disorders

Psychiatric disorders Insomnia**

Nervous system Headache Dizzinessdisorders Dysgeusia

Cardiac disorders Tachycardia

Gastrointestinal Nausea Dry mouth Pancreatitis*** Intestinaldisorders Vomiting Dyspepsia Delayed gastric obstruction†

Diarrhoea Gastritis emptying****

Constipation Gastro-oesophagealreflux disease

Abdominal pain upper

Flatulence

Eructation

Abdominal distension

Hepatobiliary Cholelithiasis*** Cholecystitis***disorders

Skin and Rash Urticaria Cutaneoussubcutaneous tissue amyloidosisdisorders

Renal and urinary Acute renaldisorders failure

Renalimpairment

General disorders Injection site reactions Malaiseand administration Astheniasite conditions Fatigue

Investigations Increased lipase

Increased amylase

*Hypoglycaemia (based on self-reported symptoms by patients and not confirmed by blood glucose measurements) reportedin patients without type 2 diabetes mellitus treated with Saxenda in combination with diet and exercise. Please see section‘Description of selected adverse reactions’ for further information.

**Insomnia was mainly seen during the first 3 months of treatment.

***See section 4.4.

****From controlled phase 2, 3a and 3b clinical trials.†ADR from post marketing sources.

In clinical trials in overweight or obese patients without type 2 diabetes mellitus treated with Saxendain combination with diet and exercise, no severe hypoglycaemic events (requiring third partyassistance) were reported. Symptoms of hypoglycaemic events were reported by 1.6% of patientstreated with Saxenda and 1.1% of patients treated with placebo; however, these events were notconfirmed by blood glucose measurements. The majority of events were mild.

In a clinical trial in overweight or obese patients with type 2 diabetes mellitus treated with Saxenda incombination with diet and exercise, severe hypoglycaemia (requiring third party assistance) wasreported by 0.7% of patients treated with Saxenda and only in patients concomitantly treated withsulfonylurea. Also, in these patients documented symptomatic hypoglycaemia was reported by 43.6%of patients treated with Saxenda and in 27.3% of patients treated with placebo. Among patients notconcomitantly treated with sulfonylurea, 15.7% of patients treated with Saxenda and 7.6% of patientstreated with placebo reported documented symptomatic hypoglycaemic events (defined as plasmaglucose ≤ 3.9 mmol/L accompanied by symptoms).

In a clinical trial in overweight or obese patients with type 2 diabetes mellitus treated with insulin andliraglutide 3.0 mg/day in combination with diet and exercise and up to 2 OADs, severe hypoglycaemia(requiring third party assistance) was reported by 1.5% of patients treated with liraglutide 3.0 mg/day.

In this trial, documented symptomatic hypoglycaemia (defined as plasma glucose ≤ 3.9 mmol/Laccompanied by symptoms) was reported by 47.2% of patients treated with liraglutide 3.0 mg/day andby 51.8% of patients treated with placebo. Among patients concomitantly treated with sulfonylurea,60.9% of patients treated with liraglutide 3.0 mg/day and 60.0% of patients treated with placeboreported documented symptomatic hypoglycaemic events.

Most episodes of gastrointestinal events were mild to moderate, transient and the majority did not leadto discontinuation of therapy. The reactions usually occurred during the first weeks of treatment anddiminished within a few days or weeks on continued treatment.

Patients ≥ 65 years of age may experience more gastrointestinal effects when treated with Saxenda.

Patients with mild or moderate renal impairment (creatinine clearance ≥ 30 ml/min) may experiencemore gastrointestinal effects when treated with Saxenda.

In patients treated with GLP-1 receptor agonists, there have been reports of acute renal failure. Amajority of the reported events occurred in patients who had experienced nausea, vomiting ordiarrhoea leading to volume depletion (see section 4.4).

Few cases of anaphylactic reactions with symptoms such as hypotension, palpitations, dyspnoea andoedema have been reported with marketed use of liraglutide. Anaphylactic reactions may potentiallybe life threatening. If an anaphylactic reaction is suspected, liraglutide should be discontinued andtreatment should not be restarted (see section 4.3).

Injection site reactions have been reported in patients treated with Saxenda. These reactions wereusually mild and transitory and the majority disappeared during continued treatment.

In clinical trials, tachycardia was reported in 0.6% of patients treated with Saxenda and in 0.1% ofpatients treated with placebo. The majority of events were mild or moderate. Events were isolated andthe majority resolved during continued treatment with Saxenda.

Cutaneous amyloidosis

Cutaneous amyloidosis may occur at the injection site (see section 4.2).

In a clinical trial conducted in adolescents of 12 years to less than 18 years with obesity, 125 patientswere exposed to Saxenda for 56 weeks.

Overall, the frequency, type and severity of adverse reactions in the adolescents with obesity werecomparable to that observed in the adult population. Vomiting occurred with a 2-fold higher frequencyin adolescents compared to adults.

The percentage of patients reporting at least one episode of clinically significant hypoglycaemia washigher with liraglutide (1.6%) compared to placebo (0.8%). No severe hypoglycaemic episodesoccurred in the trial.

In a clinical trial conducted in children of 6 to less than 12 years with obesity (Trial 4392), 56 patientswere exposed to Saxenda for 56 weeks.

Overall, the frequency, type and severity of adverse reactions in the children with obesity werecomparable to that observed in the adolescent and adult population.

Children reported more GI events in both liraglutide and placebo groups compared to adolescents andadults, with a 2-fold increase in vomiting observed in children compared to adolescents.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

From clinical trials and post-marketing use of liraglutide overdoses have been reported up to 72 mg(24 times the recommended dose for weight management). Events reported included severe nausea,severe vomiting and severe hypoglycaemia.

In the event of overdose, appropriate supportive treatment should be initiated according to thepatient’s clinical signs and symptoms. The patient should be observed for clinical signs of dehydrationand blood glucose should be monitored.

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

ATC code: A10BJ02

Liraglutide is an acylated human glucagon-like peptide-1 (GLP-1) analogue with 97% amino acidsequence homology to endogenous human GLP-1. Liraglutide binds to and activates the GLP-1receptor (GLP-1R).

GLP-1 is a physiological regulator of appetite and food intake, but the exact mechanism of action isnot entirely clear. In animal studies, peripheral administration of liraglutide led to uptake in specificbrain regions involved in regulation of appetite, where liraglutide, via specific activation of the 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 andkidneys. In mouse models of atherosclerosis, liraglutide prevented aortic plaque progression andreduced 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.

Liraglutide lowers body weight in humans mainly through loss of fat mass with relative reductions invisceral fat being greater than for subcutaneous fat loss. Liraglutide regulates appetite by increasingfeelings of fullness and satiety, while lowering feelings of hunger and prospective food consumption,thereby leading to reduced food intake. Liraglutide does not increase energy expenditure compared toplacebo.

Liraglutide stimulates insulin secretion and lowers glucagon secretion in a glucose-dependent mannerwhich results in a lowering of fasting and post-prandial glucose. The glucose-lowering effect is morepronounced in patients with prediabetes and diabetes compared to patients with normoglycaemia.

Clinical trials suggest that liraglutide improves and sustains beta-cell function, according to HOMA-Band the proinsulin-to-insulin ratio.

The efficacy and safety of liraglutide for weight management in conjunction with reduced calorieintake and increased physical activity were studied in four phase 3 randomised, double-blind, placebo-controlled trials which included a total of 5 358 adult patients.

* Trial 1 (SCALE Obesity & Pre-Diabetes - 1839): A total of 3 731 patients with obesity (BMI≥ 30 kg/m²) or with overweight (BMI ≥ 27 kg/m²) with dyslipidaemia and/or hypertension werestratified according to prediabetes status at screening and BMI at baseline (≥ 30 kg/m² or< 30 kg/m²). All 3 731 patients were randomised to 56 weeks of treatment and the 2 254patients with prediabetes at screening were randomised to 160 weeks of treatment. Bothtreatment periods were followed by a 12-week off drug/placebo observational follow-up period.

Lifestyle intervention in the form of an energy-restricted diet and exercise counselling wasbackground therapy for all patients.

The 56-week part of trial 1 assessed body weight loss in all the 3 731 randomised patients(2 590 completers).

The 160-week part of trial 1 assessed time to onset of type 2 diabetes in the 2 254 randomisedpatients with prediabetes (1 128 completers).

* Trial 2 (SCALE Diabetes - 1922): A 56-week trial assessing body weight loss in 846randomised (628 completers) obese and overweight patients with insufficiently controlled type2 diabetes mellitus (HbA1c range 7-10%). The background treatment at trial start was either dietand exercise alone, metformin, a sulfonylurea, a glitazone as single agents or any combinationhereof.

* Trial 3 (SCALE Sleep Apnoea - 3970): A 32-week trial assessing sleep apnoea severity andbody weight loss in 359 randomised (276 completers) obese patients with moderate or severeobstructive sleep apnoea.

* Trial 4 (SCALE Maintenance - 1923): A 56-week trial assessing body weight maintenanceand weight loss in 422 randomised (305 completers) obese and overweight patients withhypertension or dyslipidaemia after a preceding weight loss of ≥ 5% induced by a low-caloriediet.

Superior weight loss was achieved with liraglutide compared to placebo in obese/overweight patientsin all groups studied. Across the trial populations, greater proportions of the patients achieved ≥ 5%and > 10% weight loss with liraglutide than with placebo (tables 5-7). In the 160-weeks part of trial 1,the weight loss occurred mainly in the first year and was sustained throughout 160 weeks. In trial 4,more patients maintained the weight loss achieved prior to treatment initiation with liraglutide thanwith placebo (81.4% and 48.9%, respectively). Specific data on weight loss, responders, time courseand cumulative distribution of weight change (%) for trials 1-4 are presented in tables 5-9 and figures1, 2 and 3.

Early responders were defined as patients who achieved ≥ 5% weight loss after 12 weeks on treatmentdose of liraglutide (4 weeks of dose escalation and 12 weeks on treatment dose). In the 56-week partof trial 1, 67.5% achieved ≥ 5% weight loss after 12 weeks. In trial 2, 50.4% achieved ≥ 5% weightloss after 12 weeks. With continued treatment with liraglutide, 86.2% of these early responders arepredicted to achieve a weight loss of ≥ 5% and 51% are predicted to achieve a weight loss of ≥ 10%after 1 year of treatment. The predicted mean weight loss in early responders who complete 1 year oftreatment is 11.2% of their baseline body weight (9.7% for males and 11.6% for females). For patientswho have achieved a weight loss of < 5% after 12 weeks on treatment dose of liraglutide, theproportion of patients not reaching a weight loss of ≥ 10% after 1 year is 93.4%.

Treatment with liraglutide significantly improved glycaemic parameters across sub-populations withnormoglycaemia, prediabetes and type 2 diabetes mellitus. In the 56-week part of trial 1, fewerpatients treated with liraglutide had developed type 2 diabetes mellitus compared to patients treatedwith placebo (0.2% vs. 1.1%). More patients with prediabetes at baseline had reversed theirprediabetes compared to patients treated with placebo (69.2% vs. 32.7%). In the 160-week part of trial1, the primary efficacy endpoint was the proportion of patients with onset of type 2 diabetes mellitusevaluated as time to onset. At week 160, while on treatment, 3% treated with Saxenda and 11% treatedwith placebo were diagnosed with type 2 diabetes mellitus. The estimated time to onset of type 2diabetes mellitus for patients treated with liraglutide 3.0 mg was 2.7 times longer (with a 95%confidence interval of [1.9, 3.9]), and the hazard ratio for risk of developing type 2 diabetes mellituswas 0.2 for liraglutide versus placebo.

Treatment with liraglutide significantly improved systolic blood pressure and waist circumferencecompared with placebo (tables 5, 6 and 7).

Treatment with liraglutide significantly reduced the severity of obstructive sleep apnoea as assessed bychange from baseline in the AHI compared with placebo (table 8).

Table 5 Trial 1: Changes from baseline in body weight, glycaemia and cardiometabolicparameters at week 56

Saxenda (N=2437) Placebo (N=1225) Saxenda vs. placebo

Baseline, kg (SD) 106.3 (21.2) 106.3 (21.7) -

Mean change at week 56, % (95% CI) -8.0 -2.6 -5.4** (-5.8; -5.0)

Mean change at week 56, kg (95% CI) -8.4 -2.8 -5.6** (-6.0; -5.1)

Proportion of patients losing ≥ 5% body **weight at week 56, % (95% CI) 63.5 26.6 4.8 (4.1; 5.6)

Proportion of patients losing > 10% body **weight at week 56, % (95% CI) 32.8 10.1 4.3 (3.5; 5.3)

Glycaemia and cardiometabolic factors Baseline Change Baseline Change

HbA1c, % 5.6 -0.3 5.6 -0.1 -0.23** (-0.25; -0.21)

FPG, mmol/L 5.3 -0.4 5.3 -0.01 -0.38** (-0.42; -0.35)

Systolic blood pressure, mmHg 123.0 -4.3 123.3 -1.5 -2.8** (-3.6; -2.1)

Diastolic blood pressure, mmHg 78.7 -2.7 78.9 -1.8 -0.9* (-1.4; -0.4)

Waist circumference, cm 115.0 -8.2 114.5 -4.0 -4.2** (-4.7; -3.7)

Full Analysis Set. For body weight, HbA1c, FPG, blood pressure and waist circumference, baseline values are means, changesfrom baseline at week 56 are estimated means (least-squares) and treatment contrasts at week 56 are estimated treatmentdifferences. For the proportions of patients losing ≥ 5/> 10% body weight, estimated odds ratios are presented. Missing post-baseline values were imputed using the last observation carried forward. * p< 0.05. ** p< 0.0001. CI=confidence interval.

FPG=fasting plasma glucose. SD=standard deviation.

Table 6 Trial 1: Changes from baseline in body weight, glycaemia and cardiometabolicparameters at week 160

Saxenda (N=1472) Placebo (N=738) Saxenda vs. placebo

B aseline, kg (SD) 107.6 (21.6) 108.0 (21.8)

Mean change at week 160, % (95% CI) -6.2 -1.8 -4.3** (-4.9; -3.7)

Mean change at week 160, kg (95% CI) -6.5 -2.0 -4.6** (-5.3; -3.9)

Proportion of patients losing ≥ 5% body **weight at week 160, % (95% CI) 49.6 23.4 3.2 (2.6; 3.9)

Proportion of patients losing > 10% bodyweight at week 160, % (95% CI) 24.4 9.5 3.1** (2.3; 4.1)

Glycaemia and cardiometabolic factors Baseline Change Baseline Change

HbA1c, % 5.8 -0.4 5.7 -0.1 -0.21** (-0.24; -0.18)

FPG, mmol/L 5.5 -0.4 5.5 0.04 - 0.4** (-0.5; -0.4)

Systolic blood pressure, mmHg 124.8 -3.2 125.0 -0.4 -2.8** (-3.8; -1.8)

Diastolic blood pressure, mmHg 79.4 -2.4 79.8 -1.7 -0.6 (-1.3; 0.1)

Waist circumference, cm 116.6 -6.9 116.7 -3.4 - 3.5** (-4.2; -2.8)

Full Analysis Set. For body weight, HbA1c, FPG, blood pressure and waist circumference, baseline values are means, changesfrom baseline at week 160 are estimated means (least-squares) and treatment contrasts at week 160 are estimated treatmentdifferences. For the proportions of patients losing ≥ 5/> 10% body weight, estimated odds ratios are presented. Missing post-baseline values were imputed using the last observation carried forward. ** p< 0.0001. CI=confidence interval. FPG=fastingplasma glucose. SD=standard deviation.

Time in weeks

Saxenda Placebo Last observation carried forward (LOCF)

Observed values for patients completing each scheduled visit

Figure 1 Change from baseline in body weight (%) by time in trial 1 (0-56 weeks)

Change in Body Weight (%)

Saxenda Placebo

Last observation carried forward.

Figure 2 Cumulative distribution of weight change (%) after 56 weeks of treatment in trial 1

Table 7 Trial 2: Changes from baseline in body weight, glycaemia and cardiometabolicparameters at week 56

Saxenda (N=412) Placebo (N=211) Saxenda vs. placebo

Baseline, kg (SD) 105.6 (21.9) 106.7 (21.2) -

Mean change at week 56, % (95% CI) -5.9 -2.0 -4.0** (-4.8; -3.1)

Mean change at week 56, kg (95% CI) -6.2 -2.2 -4.1** (-5.0; -3.1)

Proportion of patients losing ≥ 5% body **weight at week 56, % (95% CI) 49.8 13.5 6.4 (4.1; 10.0)

Proportion of patients losing > 10% body **weight at week 56, % (95% CI) 22.9 4.2 6.8 (3.4; 13.8)

Glycaemia and cardiometabolic factors Baseline Change Baseline Change

HbA1c, % 7.9 -1.3 7.9 -0.4 -0.9** (-1.1; -0.8)

FPG, mmol/L 8.8 -1.9 8.6 -0.1 -1.8** (-2.1; -1.4)

Systolic blood pressure, mmHg 128.9 -3.0 129.2 -0.4 -2.6* (-4.6; -0.6)

Diastolic blood pressure, mmHg 79.0 -1.0 79.3 -0.6 -0.4 (-1.7; 1.0)

Waist circumference, cm 118.1 -6.0 117.3 -2.8 -3.2** (-4.2; -2.2)

Cumulative Frequency (%) Change in Body Weight (%)

Full Analysis Set. For body weight, HbA1c, FPG, blood pressure and waist circumference, baseline values are means, changesfrom baseline at week 56 are estimated means (least-squares) and treatment contrasts at week 56 are estimated treatmentdifferences. For the proportions of patients losing ≥ 5/> 10% body weight, estimated odds ratios are presented. Missing post-baseline values were imputed using the last observation carried forward. * p< 0.05. ** p< 0.0001. CI=confidence interval.

FPG=fasting plasma glucose. SD=standard deviation.

Table 8 Trial 3: Changes from baseline in body weight and Apnoea-Hypopnoea Index at week

Saxenda (N=180) Placebo (N=179) Saxenda vs. placebo

Baseline, kg (SD) 116.5 (23.0) 118.7 (25.4) -

Mean change at week 32, % (95% CI) -5.7 -1.6 -4.2** (-5.2; -3.1)

Mean change at week 32, kg (95% CI) -6.8 -1.8 -4.9** (-6.2; -3.7)

Proportion of patients losing ≥ 5% bodyweight at week 32, % (95% CI) 46.4 18.1 3.9** (2.4; 6.4)

Proportion of patients losing > 10% body **weight at week 32 % (95% CI) 22.4 1.5 19.0 (5.7; 63.1)

Baseline Change Baseline Change

Apnoea-Hypopnoea Index, events/hour 49.0 -12.2 49.3 -6.1 -6.1* (-11.0; -1.2)

Full Analysis Set. Baseline values are means, changes from baseline at week 32 are estimated means (least-squares) andtreatment contrasts at week 32 are estimated treatment differences (95% CI). For the proportions of patients losing ≥ 5/> 10%body weight, estimated odds ratios are presented. Missing post-baseline values were imputed using the last observationcarried forward. * p< 0.05. ** p< 0.0001. CI=confidence interval. SD=standard deviation.

Table 9 Trial 4: Changes from baseline in body weight at week 56

Saxenda (N=207) Placebo (N=206) Saxenda vs. placebo

Baseline, kg (SD) 100.7 (20.8) 98.9 (21.2) -

Mean change at week 56, % (95% CI) -6.3 -0.2 -6.1** (-7.5; -4.6)

Mean change at week 56, kg (95% CI) -6.0 -0.2 -5.9** (-7.3; -4.4)

Proportion of patients losing ≥ 5% bodyweight at week 56, % (95% CI) 50.7 21.3 3.8** (2.4; 6.0)

Proportion of patients losing > 10% body **weight at week 56, % (95% CI) 27.4 6.8 5.1 (2.7; 9.7)

Full Analysis Set. Baseline values are means, changes from baseline at week 56 are estimated means (least-squares) andtreatment contrasts at week 56 are estimated treatment differences. For the proportions of patients losing ≥ 5/> 10% bodyweight, estimated odds ratios are presented. Missing post-baseline values were imputed using the last observation carriedforward. ** p< 0.0001. CI=confidence interval. SD=standard deviation.

Time in weeks

Saxenda Placebo Last observation carried forward (LOCF)

Observed values for patients completing each scheduled visit

Figure 3 Change from randomisation (week 0) in body weight (%) by time in trial 4

Change in Body Weight (%)

Before week 0 patients were only treated with low-calorie diet and exercise. At week 0 patients wererandomised to receive either Saxenda or placebo.

Consistent with the potentially immunogenic properties of protein and peptide pharmaceuticals,patients may develop anti-liraglutide antibodies following treatment with liraglutide. In clinical trials,2.5% of patients treated with liraglutide developed anti-liraglutide antibodies. Antibody formation hasnot been associated with reduced efficacy of liraglutide.

Major adverse cardiovascular events (MACE) were adjudicated by an external independent group ofexperts and defined as non-fatal myocardial infarction, non-fatal stroke and cardiovascular death. In allthe long-term clinical trials with Saxenda, there were 6 MACE for patients treated with liraglutide and10 MACE for placebo-treated patients. The hazard ratio and 95% CI is 0.33 [0.12; 0.90] for liraglutideversus placebo. A mean increase in heart rate from baseline of 2.5 beats per minute (ranging acrosstrials from 1.6 to 3.6 beats per minute) has been observed with liraglutide in clinical phase 3 trials. Theheart rate peaked after approximately 6 weeks. The long-term clinical impact of this mean increase inheart rate has not been established. The change in heart rate was reversible upon discontinuation ofliraglutide (see section 4.4).

The Liraglutide Effect and Action in Diabetes Evaluation of Cardiovascular Outcomes Results(LEADER) trial included 9 340 patients with insufficiently controlled type 2 diabetes. The vastmajority of these had established cardiovascular disease. Patients were randomly allocated to eitherliraglutide on a daily dose of up to 1.8 mg (4 668) or placebo (4 672), both on a background ofstandard of care.

The duration of exposure was between 3.5 and 5 years. The mean age was 64 years and the mean BMIwas 32.5 kg/m². Mean baseline HbA1c was 8.7 and had improved after 3 years by 1.2 % in patientsassigned to liraglutide and by 0.8 % in patients assigned to placebo. The primary endpoint was thetime from randomisation to first occurrence of any major adverse cardiovascular events (MACE):cardiovascular death, non-fatal myocardial infarction or non-fatal stroke.

Liraglutide significantly reduced the rate of major adverse cardiovascular events (primary endpointevents, MACE) vs. placebo (3.41 vs. 3.90 per 100 patient years of observation in the liraglutide andplacebo groups, respectively) with a risk reduction of 13%, HR 0.87, [0.78, 0.97] [95% CI]) (p=0.005)(see figure 4).

Placebo

Liraglutide

HR: 0.8795% CI 0.78; 0.97p<0.001 for non-inferiorityp=0.005 for superiority

Time from randomization (months)

Patients at risk

Placebo 4672 4587 4473 4352 4237 4123 4010 3914 1543 407

Liraglutide 4668 4593 4496 4400 4280 4172 4072 3982 1562 424

FAS: full analysis set.

Figure 4 Kaplan Meier plot of time to first MACE - FAS population

Patients with an event (%)

In a double-blind trial comparing the efficacy and safety of Saxenda versus placebo on weight loss inadolescent patients aged 12 years and above with obesity, Saxenda was superior to placebo in weightreduction (evaluated as BMI Standard Deviation Score) after 56 weeks of treatment (table 10).

A greater proportion of the patients achieved ≥ 5% and ≥ 10% reductions in BMI with liraglutide thanwith placebo, as well as greater reductions in mean BMI and body weight (table 10). After 26 weeksof off-trial product follow-up period, weight regain was observed with liraglutide vs placebo (table10).

Table 10 Trial 4180: Changes from baseline in body weight and BMI at week 56 and change in

BMI SDS from week 56 to week 82

Saxenda (N=125) Placebo (N=126) Saxenda vs. placebo

BMI SDS

Baseline, BMI SDS (SD) 3.14 (0.65) 3.20 (0.77)

Mean change at week 56 (95% CI) -0.23 0.00 -0.22* (-0.37; -0.08)

Week 56, BMI SDS (SD) 2.88 (0.94) 3.14 (0.98)

Mean change from week 56 to week **82, BMI SDS (95% CI) 0.22 0.07 0.15 (0.07; 0.23)

Baseline, kg (SD) 99.3 (19.7) 102.2 (21.6) -

Mean change at week 56, % (95% CI) -2.65 2.37 -5.01** (-7.63; -2.39)

Mean change at week 56, kg (95% CI) -2.26 2.25 -4.50** (-7.17; -1.84)

BMI

Baseline, kg/m2 (SD) 35.3 (5.1) 35.8 (5.7) -

Mean change at week 56, kg/m2 (95% -1.39 0.19 -1.58** (-2.47; -0.69)

CI)

Proportion of patients with ≥ 5%reduction in baseline BMI at week 56, 43.25 18.73 3.31** (1.78; 6.16)% (95% CI)

Proportion of patients with ≥ 10%reduction in baseline BMI at week 56, 26.08 8.11 4.00** (1.81; 8.83)% (95% CI)

Full Analysis Set. For BMI SDS, body weight and BMI, baseline values are means, changes from baseline at week 56 areestimated means (least-squares) and treatment contrasts at week 56 are estimated treatment differences. For BMI SDS, valueat week 56 are means, changes from week 56 to week 82 are estimated means (least-squares) and treatment contrasts at week82 are estimated treatment differences. For the proportions of patients losing ≥ 5%/≥ 10% baseline BMI, estimated oddsratios are presented. Missing observations were imputed from the placebo arm based on a jump to reference multiple (x100)imputation approach.

*p< 0.01, **p< 0.001. CI=confidence interval. SD=standard deviation.

Based on tolerability, 103 patients (82.4%) escalated and remained on dose of 3.0 mg, 11 patients(8.8%) escalated and remained on dose of 2.4 mg, 4 patients (3.2%) escalated and remained on dose of1.8 mg, 4 patients (3.2%) escalated and remained on dose of 1.2 mg and 3 patients (2.4%) remained ondose of 0.6 mg.

No effects on growth or pubertal development were found after 56 weeks of treatment.

A 16-week double-blind, 36 week open-label study was conducted to evaluate the efficacy and safetyof Saxenda in paediatric patients with Prader-Willi Syndrome and obesity. The study included32 patients between 12 to < 18 years of age (part A) and 24 patients between 6 to < 12 years of age(part B). Patients were randomized 2:1 to receive Saxenda or placebo. Patients with a body weight lessthan 45 kg started dose escalation at a lower dose; 0.3 mg instead of 0.6 mg and were escalated to amaximum dose of 2.4 mg.

The estimated treatment difference in mean BMI SDS at 16 weeks (part A: -0.20 vs -0.13, part

B: -0.50 vs -0.44) and 52 weeks (part A: -0.31 vs -0.17, part B: -0.73 vs -0.67) were similar with

Saxenda and placebo.

No additional safety concerns were seen in the trial.

A 56-week double-blinded trial 82 children, aged 6 to <12 years, with obesity were randomised 2:1 toreceive liraglutide 3.0 mg or placebo once daily. All patients received counselling in healthy nutritionand physical activity throughout the trial.

At end of treatment (week 56), the improvement in BMI with liraglutide was superior and clinicallymeaningful compared with placebo (see Table 11). Furthermore, a higher proportion of patientsachieved ≥5% BMI reduction with Liraglutide compared with placebo (see Table 11).

Table 11 SCALE KIDS 4392: Results at week 56

SAXENDA Placebo SAXENDA vs Placebo(N=56) (N=26)

BMI

Baseline mean BMI, kg/m2 (SD) 30.9 (4.7) 31.3 (7.0)

Mean Change from Baseline, % (95% CI) -5.80 1.60 -7.40 (-11.56, -3.24)

Proportion of patients with ≥ to 5%reduction in baseline BMI at week 56, 46.2% 8.7% 6.27 (1.36, 28.79)

OR (95% CI)

Body Weight

Baseline mean body weight, kg (SD) 69.8 (17.7) 71.0 (23.2)

Mean Change from Baseline, % (95% CI) 1.59 9.96 -8.37 (-13.39, -3.34)

BMI: Body mass index, SD: Standard deviation, CI: Confidence interval.

For BMI and body weight, baseline values are means, changes from baseline at week 56 are estimated means (least-squares)and treatment contrasts at week 56 are estimated treatment differences. For the proportions of patients losing ≥5% baseline

BMI, estimated odds ratios are presented.

ANCOVA: Week 56 responses were analyzed using an analysis of covariance model with randomised treatment,stratification groups (gender and Tanner stage at baseline) and the interaction between stratification groups as factors andbaseline of respective endpoint as covariate. RD-MI: Missing observations were multiple (x1000) imputed from retrievedparticipants regardless of randomised treatment arm.

The absorption of liraglutide following subcutaneous administration was slow, reaching maximumconcentration approximately 11 hours post dosing. The average liraglutide steady state concentration(AUCτ/24) reached approximately 31 nmol/L in obese (BMI 30-40 kg/m2) patients followingadministration of 3 mg liraglutide. Liraglutide exposure increased proportionally with dose. Absolutebioavailability of liraglutide following subcutaneous administration is approximately 55%.

The mean apparent volume of distribution after subcutaneous administration is 20-25 L (for a personweighing approximately 100 kg). Liraglutide is extensively bound to plasma protein (> 98%).

During 24 hours following administration of a single [3H]-liraglutide dose to healthy subjects, themajor component in plasma was intact liraglutide. Two minor plasma metabolites were detected (≤ 9%and ≤ 5% of total plasma radioactivity exposure).

Liraglutide is endogenously metabolised in a similar manner to large proteins without a specific organas major route of elimination. Following a [3H]-liraglutide dose, intact liraglutide was not detected inurine or faeces. Only a minor part of the administered radioactivity was excreted as liraglutide-relatedmetabolites in urine or faeces (6% and 5%, respectively). The urine and faeces radioactivity wasmainly excreted during the first 6-8 days and corresponded to three minor metabolites, respectively.

The mean clearance following subcutaneous administration of liraglutide is approximately 0.9-1.4 L/hwith an elimination half-life of approximately 13 hours.

Age had no clinically relevant effect on the pharmacokinetics of liraglutide based on the results from apopulation pharmacokinetic analysis of data from overweight and obese patients (18 to 82 years). Nodosage adjustment is required based on age.

Based on the results of population pharmacokinetic analysis, females have 24% lower weight adjustedclearance of liraglutide compared to males. Based on the exposure response data, no dose adjustmentis necessary based on gender.

Ethnic origin had no clinically relevant effect on the pharmacokinetics of liraglutide based on theresults of population pharmacokinetic analysis which included overweight and obese patients of

White, Black, Asian and Hispanic/non-Hispanic groups.

The exposure of liraglutide decreases with an increase in baseline body weight. The 3.0 mg daily doseof liraglutide provided adequate systemic exposures over the body weight range of 60-234 kgevaluated for exposure response in the clinical trials. Liraglutide exposure was not studied in patientswith body weight > 234 kg.

The pharmacokinetics of liraglutide was evaluated in patients with varying degree of hepaticimpairment in a single-dose trial (0.75 mg). Liraglutide exposure was decreased by 13-23% in patientswith mild to moderate hepatic impairment compared to healthy subjects. Exposure was significantlylower (44%) in patients with severe hepatic impairment (Child Pugh score > 9).

Liraglutide exposure was reduced in patients with renal impairment compared to individuals withnormal renal function in a single-dose trial (0.75 mg). Liraglutide exposure was lowered by 33%, 14%,27% and 26%, respectively, 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 diseaserequiring dialysis.

Pharmacokinetic properties for liraglutide 3.0 mg were assessed in clinical studies for adolescentpatients with obesity aged 12 to less than 18 years (134 patients, body weight 62-178 kg). Theliraglutide exposure in adolescents (age 12 to less than 18 years) was similar to that in adults withobesity.

Pharmacokinetic properties for liraglutide 3.0 mg were also assessed in clinical studies in childrenwith obesity aged 6 to less than 12 years (59 patients, body weight 35-114 kg). The liraglutideexposure in children (aged 6 to less than 12 years) was higher than that in adults and adolescents.

After correction for body weight the exposure was similar to that in adults and adolescents.

Non-clinical data reveal no special hazard for humans based on conventional studies of safetypharmacology, repeat-dose toxicity or genotoxicity.

Non-lethal thyroid C-cell tumours were seen in two-year carcinogenicity studies in rats and mice. Inrats, a no observed adverse effect level (NOAEL) was not observed. These tumours were not seen inmonkeys 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 forhumans is likely to be low but cannot be completely excluded. No other treatment-related tumourshave been found.

Animal studies did not indicate direct harmful effects with respect to fertility but slightly increasedearly embryonic deaths at the highest dose. Dosing with liraglutide during mid-gestation caused areduction in maternal weight and foetal growth with equivocal effects on ribs in rats and skeletalvariation in the rabbit. Neonatal growth was reduced in rats while exposed to liraglutide and persistedin the post-weaning period in the high dose group. It is unknown whether the reduced pup growth iscaused by reduced pup milk intake due to a direct GLP-1 effect or reduced maternal milk productiondue to decreased caloric intake.

In juvenile rats, liraglutide caused delayed sexual maturation in both males and females at clinicalrelevant exposures. These delays had no impact upon fertility and reproductive capacity of either sex,or on the ability of the females to maintain pregnancy.

Disodium phosphate dihydrate

Phenol

Hydrochloric acid (for pH adjustment)

Sodium hydroxide (for pH adjustment)

Water for injections

Substances added to Saxenda may cause degradation of liraglutide. In the absence of compatibilitystudies, this medicinal product must not be mixed with other medicinal products.

30 months

After first use: 1 month

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).

Keep the cap on the pen in order to protect from light.

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 polypropylene,polyacetal, polycarbonate and acrylonitrile butadiene styrene.

Each pen contains 3 ml solution and is able to deliver doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg and3.0 mg.

Pack sizes of 1, 3 or 5 pre-filled pens.

Not all pack sizes may be marketed.

The solution should not be used if it does not appear clear and colourless or almost colourless.

Saxenda should not be used if it has been frozen.

The pen is designed to be used with NovoFine or NovoTwist disposable needles up to a length of8 mm and as thin as 32G.

Needles are not included.

The patient should be advised to discard the injection needle after each injection and store the penwithout an injection needle attached. This prevents contamination, infection and leakage. It alsoensures that the dosing is accurate.

Any unused medicinal product or waste material should be disposed in accordance with localrequirements.

Novo Nordisk A/S

Novo Alle 1

DK-2880 Bagsværd

Denmark

EU/1/15/992/001-003

Date of first authorisation: 23 March 2015

Date of latest renewal: 09 December 2019

Detailed information on this medicinal product is available on the website of the European Medicines

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