Onglyza

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

Onglyza 2.5 mg film-coated tablets
Onglyza 5 mg film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Onglyza 2.5 mg film-coated tablets
Each tablet contains 2.5 mg saxagliptin (as hydrochloride).

Onglyza 5 mg film-coated tablets
Each tablet contains 5 mg saxagliptin (as hydrochloride).

Excipient(s) with known effect:
Each tablet contains 99 mg lactose (as monohydrate).
Onglyza contains less than 1 mmol sodium (23 mg) per dose, i.e. is essentially ‘sodium-free’.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet (tablet).

Onglyza 2.5 mg film-coated tablets
Onglyza 2.5 mg tablets are pale yellow to light yellow, biconvex, round, film-coated tablets, with 
“2.5” printed on one side and “4214” printed on the other side, in blue ink.

Onglyza 5 mg film-coated tablets
Onglyza 5 mg tablets are pink, biconvex, round, film-coated tablets, with “5” printed on one side and 
“4215” printed on the other side, in blue ink.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Onglyza is indicated in adult patients with type 2 diabetes mellitus as an adjunct to diet and exercise to 
improve glycaemic control:

 as monotherapy when metformin is inappropriate due to intolerance or contraindications

 in combination with other medicinal products for the treatment of diabetes, including insulin,
when these do not provide adequate glycaemic control (see sections 4.4, 4.5 and 5.1 for 
available data on different combinations).

4.2 Posology and method of administration

Posology

The recommended dose of Onglyza is 5 mg once daily. When Onglyza is used in combination with 
insulin or a sulphonylurea, a lower dose of the insulin or sulphonylurea may be required to reduce the 
risk of hypoglycaemia (see section 4.4).

The safety and efficacy of saxagliptin as triple oral therapy in combination with metformin and a 
thiazolidinedione have not been established.



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Special populations
Elderly (≥ 65 years)
No dose adjustment is recommended based solely on age (see also sections 5.1 and 5.2).

Renal impairment
No dose adjustment is recommended for patients with mild renal impairment or in patients with 
moderate renal impairment that have GFR ≥ 45 mL/min.

The dose should be reduced to 2.5 mg once daily in patients with moderate renal impairment that have 
GFR < 45 mL/min and in patients with severe renal impairment.

Onglyza is not recommended for patients with end-stage renal disease (ESRD) requiring 
haemodialysis (see section 4.4).

Because the dose should be limited to 2.5 mg based upon renal function, assessment of renal function 
is recommended prior to initiation of treatment, and, in keeping with routine care, renal assessment 
should be done periodically thereafter (see sections 4.4 and 5.2).

Hepatic impairment
No dose adjustment is necessary for patients with mild or moderate hepatic impairment (see 
section 5.2). Saxagliptin should be used with caution in patients with moderate hepatic impairment, 
and is not recommended for use in patients with severe hepatic impairment (see section 4.4).

Paediatric population
The safety and efficacy of Onglyza in children aged birth to < 18 years have not yet been established. 
No data are available.

Method of administration
The tablets can be taken with or without a meal at any time of the day. Tablets must not be split or cut.

If a dose is missed, it should be taken as soon as the patient remembers. A double dose should not be 
taken on the same day.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1, or history of a 
serious hypersensitivity reaction, including anaphylactic reaction, anaphylactic shock, and 
angioedema, to any dipeptidyl peptidase-4 (DPP4) inhibitor (see sections 4.4 and 4.8).

4.4 Special warnings and precautions for use

General
Onglyza should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic 
ketoacidosis.

Onglyza is not a substitute for insulin in insulin-requiring patients.

Acute Pancreatitis
Use of DPP4 inhibitors has been associated with a risk of developing acute pancreatitis. Patients 
should be informed of the characteristic symptoms of acute pancreatitis; persistent, severe abdominal 
pain. If pancreatitis is suspected, Onglyza should be discontinued; if acute pancreatitis is confirmed, 
Onglyza should not be restarted. Caution should be exercised in patients with a history of pancreatitis.

In postmarketing experience of saxagliptin, there have been spontaneously reported adverse reactions 
of acute pancreatitis. 



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Renal impairment
In patients with GFR < 45 mL/min, the recommended dose is 2.5 mg once daily. Saxagliptin is not 
recommended for use in patients with end-stage renal disease (ESRD) requiring haemodialysis. 
Assessment of renal function is recommended prior to initiation of Onglyza, and in keeping with 
routine care, renal assessment should be done periodically thereafter (see sections 4.2 and 5.2).

Hepatic impairment
Saxagliptin should be used with caution in patients with moderate hepatic impairment, and is not 
recommended for use in patients with severe hepatic impairment (see section 4.2).

Use with medicinal products known to cause hypoglycaemia
Sulphonylureas and insulin are known to cause hypoglycaemia. Therefore, a lower dose of 
sulphonylurea or insulin may be required to reduce the risk of hypoglycaemia when used in 
combination with Onglyza.

Hypersensitivity reactions
Onglyza must not be used in patients who have had any serious hypersensitivity reaction to a 
dipeptidyl peptidase-4 (DPP4) inhibitor (see section 4.3).

During postmarketing experience, including spontaneous reports and clinical trials, the following 
adverse reactions have been reported with the use of saxagliptin: serious hypersensitivity reactions, 
including anaphylactic reaction, anaphylactic shock, and angioedema. If a serious hypersensitivity 
reaction to saxagliptin is suspected, Onglyza should be discontinued, assess for other potential causes 
for the event, and institute alternative treatment for diabetes (see section 4.8).

Skin disorders
Ulcerative and necrotic skin lesions have been reported in extremities of monkeys in non-clinical 
toxicology studies (see section 5.3). Skin lesions were not observed at an increased incidence in 
clinical trials. Postmarketing reports of rash have been described in the DPP4 inhibitor class. Rash is 
also noted as an adverse reaction for Onglyza (see section 4.8). Therefore, in keeping with routine care 
of the diabetic patient, monitoring for skin disorders, such as blistering, ulceration or rash, is 
recommended.

Bullous pemphigoid
Postmarketing cases of bullous pemphigoid requiring hospitalisation have been reported with DPP4
inhibitor use, including saxagliptin. In reported cases, patients typically responded to topical or 
systemic immunosuppressive treatment and discontinuation of the DPP4 inhibitor. If a patient 
develops blisters or erosions while receiving saxagliptin and bullous pemphigoid is suspected, this 
medicinal product should be discontinued and referral to a dermatologist should be considered for 
diagnosis and appropriate treatment (see section 4.8).

Cardiac failure
Experience in NYHA class III-IV is still limited. In the SAVOR trial a small increase in the rate for 
hospitalisation for heart failure was observed in the saxagliptin treated patients compared to placebo, 
although a causal relationship has not been established (see section 5.1). Additional analysis did not 
indicate a differential effect among NYHA classes. Caution is warranted if Onglyza is used in patients 
who have known risk factors for hospitalisation for heart failure, such as a history of heart failure or 
moderate to severe renal impairment. Patients should be advised of the characteristic symptoms of 
heart failure, and to immediately report such symptoms.

Arthralgia
Joint pain, which may be severe, has been reported in postmarketing reports for DPP4 inhibitors (see 
section 4.8). Patients experienced relief of symptoms after discontinuation of the medication and some 
experienced recurrence of symptoms with reintroduction of the same or another DPP4 inhibitor. Onset 
of symptoms following initiation of drug therapy may be rapid or may occur after longer periods of 
treatment. If a patient presents with severe joint pain, continuation of drug therapy should be 
individually assessed.



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Immunocompromised patients
Immunocompromised patients, such as patients who have undergone organ transplantation or patients 
diagnosed with human immunodeficiency syndrome, have not been studied in the Onglyza clinical 
program. Therefore, the efficacy and safety profile of saxagliptin in these patients has not been 
established.

Use with potent CYP3A4 inducers
Using CYP3A4 inducers like carbamazepine, dexamethasone, phenobarbital, phenytoin, and 
rifampicin may reduce the glycaemic lowering effect of Onglyza (see section 4.5).

Lactose
The tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose 
intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal 
product.

4.5 Interaction with other medicinal products and other forms of interaction

Clinical data described below suggest that the risk for clinically meaningful interactions with 
co-administered medicinal products is low.

The metabolism of saxagliptin is primarily mediated by cytochrome P450 3A4/5 (CYP3A4/5).

The co-administration of saxagliptin and CYP3A4/5 inducers, other than rifampicin (such as 
carbamazepine, dexamethasone, phenobarbital and phenytoin) have not been studied and may result in 
decreased plasma concentration of saxagliptin and increased concentration of its major metabolite. 
Glycaemic control should be carefully assessed when saxagliptin is used concomitantly with a potent 
CYP3A4/5 inducer.

Concomitant administration of saxagliptin with the moderate inhibitor of CYP3A4/5 diltiazem, 
increased the Cmax and AUC of saxagliptin by 63% and 2.1-fold, respectively, and the corresponding 
values for the active metabolite were decreased by 44% and 34%, respectively. 

Concomitant administration of saxagliptin with the potent inhibitor of CYP3A4/5 ketoconazole, 
increased the Cmax and AUC of saxagliptin by 62% and 2.5-fold, respectively, and the corresponding 
values for the active metabolite were decreased by 95% and 88%, respectively.

Concomitant administration of saxagliptin with the potent CYP3A4/5 inducer rifampicin, reduced Cmax
and AUC of saxagliptin by 53% and 76%, respectively. The exposure of the active metabolite and the 
plasma DPP4 activity inhibition over a dose interval were not influenced by rifampicin (see 
section 4.4).

In in vitro studies, saxagliptin and its major metabolite neither inhibited CYP1A2, 2A6, 2B6, 2C8, 
2C9, 2C19, 2D6, 2E1, or 3A4, nor induced CYP1A2, 2B6, 2C9, or 3A4. In studies conducted in 
healthy subjects, neither the pharmacokinetics of saxagliptin nor its major metabolite, were 
meaningfully altered by metformin, glibenclamide, pioglitazone, digoxin, simvastatin, omeprazole, 
antacids or famotidine. In addition, saxagliptin did not meaningfully alter the pharmacokinetics of 
metformin, glibenclamide, pioglitazone, digoxin, simvastatin, the active components of a combined 
oral contraceptive (ethinyl estradiol and norgestimate), diltiazem or ketoconazole.

The effects of smoking, diet, herbal products, and alcohol use on the pharmacokinetics of saxagliptin 
have not been specifically studied.



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4.6 Fertility, pregnancy and lactation

Pregnancy
The use of saxagliptin has not been studied in pregnant women. Studies in animals have shown 
reproductive toxicity at high doses (see section 5.3). The potential risk for humans is unknown. 
Onglyza should not be used during pregnancy unless clearly necessary.

Breast-feeding
It is unknown whether saxagliptin is excreted in human breast milk. Animal studies have shown 
excretion of saxagliptin and/or metabolite in milk. A risk to the suckling child cannot be excluded. A 
decision must be made whether to discontinue breast-feeding or to discontinue therapy taking into 
account the benefit of breast-feeding for the child and the benefit of therapy to the woman.

Fertility
The effect of saxagliptin on fertility in humans has not been studied. Effects on fertility were observed 
in male and female rats at high doses producing overt signs of toxicity (see section 5.3).

4.7 Effects on ability to drive and use machines

Onglyza may have a negligible influence on the ability to drive and use machines.

When driving or using machines, it should be taken into account that dizziness has been reported in 
studies with saxagliptin. In addition, patients should be alerted to the risk of hypoglycaemia when 
Onglyza is used in combination with other antidiabetic medicinal products known to cause 
hypoglycaemia (e.g. insulin, sulphonylureas).

4.8 Undesirable effects

Summary of the safety profile

The most commonly reported adverse reactions in placebo-controlled trials reported in ≥5% of patients 
treated with Onglyza 5 mg and more commonly than in patients treated with placebo are upper 
respiratory tract infection (7.7%), urinary tract infection (6.8%) and headache (6.5%).

There were 4,148 patients with type 2 diabetes, including 3,021 patients treated with Onglyza, 
randomised in six double-blind, controlled clinical safety and efficacy studies conducted to evaluate 
the effects of saxagliptin on glycaemic control. In randomised, controlled, double-blind clinical trials 
(including developmental and postmarketing experience), over 17,000 patients with type 2 diabetes 
have been treated with Onglyza.

In a pooled analysis of 1,681 patients with type 2 diabetes including 882 patients treated with Onglyza 
5 mg, randomised in five double-blind, placebo-controlled clinical safety and efficacy studies 
conducted to evaluate the effects of saxagliptin on glycaemic control, the overall incidence of adverse 
events in patients treated with saxagliptin 5 mg was similar to placebo. Discontinuation of therapy due 
to adverse events was higher in patients who received saxagliptin 5 mg as compared to placebo (3.3% 
as compared to 1.8%).

Tabulated list of adverse reactions

Adverse reactions reported in ≥ 5% of patients treated with saxagliptin 5 mg and more commonly than 
in patients treated with placebo or that were reported in ≥ 2% of patients treated with saxagliptin 5 mg 
and ≥ 1% more frequently compared to placebo from the pooled analysis of five studies of glycaemic 
control, plus an additional active-controlled study of initial combination with metformin are shown in 
Table 1.

The adverse reactions are listed by system organ class and absolute frequency. Frequencies are defined 
as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to 1/100), rare 



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(≥ 1/10,000 to 1/1,000), very rare (< 1/10,000), or not known (cannot be estimated from the available 
data).

Table 1 Frequency of adverse reactions by system organ class from clinical trials and 
postmarketing experience

System organ class

Adverse reaction

Frequency of adverse reactions by treatment regimen

Saxagliptin 
monotherapy

Saxagliptin 
with 
metformin1

Saxagliptin 
with a 
sulphonylurea 
(glibenclamide)

Saxagliptin 
with a thia-
zolidinedione 

Saxagliptin as 
add-on to 
metformin 
plus a 
sulphonylurea

Infections and 
infestations
Upper respiratory 
infection

Common Common Common Common

Urinary tract 
infection

Common Common Common Common

Gastroenteritis Common Common Common Common
Sinusitis Common Common Common Common
Naso-
pharyngitis Common2

Immune system 
disorders
Hyper-
sensitivity 
reactions†‡

Uncommon Uncommon Uncommon Uncommon

Anaphylactic 
reactions including 
anaphylactic shock†‡

Rare Rare Rare Rare

Metabolism and 
nutrition disorders
Hypo-
glycaemia

Very common3

Dyslipidaemia Uncommon
Hypertri-
glyceridaemia

Uncommon

Nervous system 
disorders
Dizziness Common Common
Headache Common Common Common Common
Gastro-
intestinal disorders
Abdominal pain† Common Common Common Common
Diarrhoea4 Common Common Common Common
Dyspepsia Common
Flatulence Common
Gastritis Common
Nausea† Common Common Common Common
Vomiting Common Common Common Common
Pancreatitis† Uncommon Uncommon Uncommon Uncommon
Constipation† Not known Not known Not known Not known Not known



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Skin and 
subcutaneous tissue 
disorders
Rash† Common Common Common
Dermatitis† Uncommon Uncommon Uncommon Uncommon
Pruritus† Uncommon Uncommon Uncommon Uncommon
Urticaria† Uncommon Uncommon Uncommon Uncommon
Angioedema†‡ Rare Rare Rare Rare
Bullous pemhigoid† Not known Not known Not known Not known Not known
Musculo-
skeletal and 
connective tissue 
disorders
Arthralgia* Uncommon
Myalgia5 Common
Reproductive 
system and breast 
disorders
Erectile dysfunction Uncommon
General disorders 
and administration 
site conditions
Fatigue Common Uncommon Common
Oedema peripheral Common
1 Includes saxagliptin in add-on to metformin and initial combination with metformin.
2 Only in the initial combination therapy.
3 There was no statistically significant difference compared to placebo. The incidence of confirmed hypoglycaemia was 
uncommon for Onglyza 5 mg (0.8%) and placebo (0.7%).
4 The incidence of diarrhoea was 4.1% (36/882) in the saxagliptin 5 mg group and 6.1% (49/799) in the placebo group.
5 As initial combination with metformin, myalgia is reported as uncommon.
† Adverse reactions were identified through postmarketing surveillance.
‡ See sections 4.3 and 4.4.
* Also reported during postmarketing surveillance (see section 4.4).

SAVOR trial results

The SAVOR trial included 8240 patients treated with Onglyza 5 mg or 2.5 mg once daily and 
8173 patients on placebo. The overall incidence of adverse events in patients treated with Onglyza in 
this trial was similar to placebo (72.5% versus 72.2%, respectively).

The incidence of adjudicated pancreatitis events was 0.3% in both Onglyza-treated patients and 
placebo-treated patients in the intent-to-treat population.

The incidence of hypersensitivity reactions was 1.1% in both Onglyza-treated patients and placebo-
treated patients.

The overall incidence of reported hypoglycaemia (recorded in daily patient diaries) was 17.1% in 
subjects treated with Onglyza and 14.8% among patients treated with placebo. The percent of subjects 
with reported on-treatment events of major hypoglycaemia (defined as an event that required 
assistance of another person) was higher in the saxagliptin group than in the placebo group (2.1% and 
1.6%, respectively). The increased risk of overall hypoglycaemia and major hypoglycaemia observed 
in the saxagliptin-treated group occurred primarily in subjects treated with SU at baseline and not in 
subjects on insulin or metformin monotherapy at baseline. The increased risk of overall and major 
hypoglycaemia was primarily observed in subjects with A1C <7% at baseline.

Decreased lymphocyte counts were reported in 0.5% of Onglyza-treated patients and 0.4% of placebo-
treated patients.



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Hospitalisation for heart failure, occurred at a greater rate in the saxagliptin group (3.5%) compared 
with the placebo group (2.8%), with nominal statistical significance favouring placebo [HR = 1.27; 
95% CI 1.07, 1.51); P = 0.007]. See also section 5.1.

Description of selected adverse reactions

Hypoglycaemia
Adverse reactions of hypoglycaemia were based on all reports of hypoglycaemia; a concurrent glucose 
measurement was not required.

When used as add-on combination therapy with metformin plus sulphonylurea, the overall incidence 
of reported hypoglycaemia was 10.1% for Onglyza 5 mg and 6.3% for placebo.

When used as add-on to insulin (with or without metformin), the overall incidence of reported 
hypoglycaemia was 18.4% for Onglyza 5 mg and 19.9% for placebo.

Investigations
Across clinical studies, the incidence of laboratory adverse events was similar in patients treated with 
saxagliptin 5 mg compared to patients treated with placebo. A small decrease in absolute lymphocyte 
count was observed. From a baseline mean absolute lymphocyte count of approximately 
2,200 cells/μl, a mean decrease of approximately 100 cells/μl relative to placebo was observed in the 
placebo-controlled-pooled analysis. Mean absolute lymphocyte counts remained stable with daily 
dosing up to 102 weeks in duration. The decreases in lymphocyte count were not associated with 
clinically relevant adverse reactions. The clinical significance of this decrease in lymphocyte count 
relative to placebo is not known.

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

Onglyza had no clinically meaningful effect on QTc interval or heart rate at oral doses up to 400 mg 
daily for 2 weeks (80 times the recommended dose). In the event of an overdose, appropriate 
supportive treatment should be initiated as dictated by the patient’s clinical status. Saxagliptin and its 
major metabolite can be removed by haemodialysis (23% of dose over 4 hours).

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs used in diabetes. Dipeptidyl peptidase 4 (DPP4) inhibitors, ATC 
code: A10BH03

Mechanism of action and pharmacodynamic effects
Saxagliptin is a highly potent (Ki: 1.3 nM), selective, reversible, competitive, DPP4 inhibitor. In 
patients with type 2 diabetes, administration of saxagliptin led to inhibition of DPP4 enzyme activity 
for a 24-hour period. After an oral glucose load, this DPP4 inhibition resulted in a 2- to 3-fold increase 
in circulating levels of active incretin hormones, including glucagon-like peptide-1 (GLP-1) and 
glucose-dependent insulinotropic polypeptide (GIP), decreased glucagon concentrations and increased 
glucose-dependent beta-cell responsiveness, which resulted in higher insulin and C-peptide 
concentrations. The rise in insulin from pancreatic beta-cells and the decrease in glucagon from 
pancreatic alpha-cells were associated with lower fasting glucose concentrations and reduced glucose 

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excursion following an oral glucose load or a meal. Saxagliptin improves glycaemic control by 
reducing fasting and postprandial glucose concentrations in patients with type 2 diabetes.

Clinical efficacy and safety
In randomised, controlled, double-blind clinical trials (including developmental and postmarketing 
experience), over 17,000 patients with type 2 diabetes have been treated with saxagliptin.

Glycaemic control
A total of 4,148 patients with type 2 diabetes, including 3,021 patients treated with saxagliptin, were 
randomised in 6 double-blind, controlled clinical safety and efficacy studies conducted to evaluate the 
effects of saxagliptin on glycaemic control. Treatment with saxagliptin 5 mg once daily produced 
clinically relevant and statistically significant improvements in haemoglobin A1c (HbA1c), fasting 
plasma glucose (FPG) and postprandial glucose (PPG) compared to placebo in monotherapy, in 
combination with metformin (initial or add-on therapy), in combination with a sulphonylurea, and in 
combination with a thiazolidinedione (see Table 2). There was also no apparent change in body weight 
associated with saxagliptin. Reductions in HbA1c were seen across subgroups including gender, age, 
race, and baseline body mass index (BMI) and higher baseline HbA1c was associated with a greater 
adjusted mean change from baseline with saxagliptin.

Saxagliptin as monotherapy
Two double-blind, placebo-controlled studies of 24-week duration were conducted to evaluate the 
efficacy and safety of saxagliptin monotherapy in patients with type 2 diabetes. In both studies, 
once-daily treatment with saxagliptin provided significant improvements in HbA1c (see Table 2). The 
findings of these studies were confirmed with two subsequent 24-week regional (Asian) monotherapy 
studies comparing saxagliptin 5 mg with placebo.

Saxagliptin add-on to metformin therapy
An add-on to metformin placebo-controlled study of 24-week duration was conducted to evaluate the 
efficacy and safety of saxagliptin in combination with metformin in patients with inadequate 
glycaemic control (HbA1c 7-10%) on metformin alone. Saxagliptin (n=186) provided significant 
improvements in HbA1c, FPG, and PPG compared to placebo (n=175). Improvements in HbA1c, 
PPG, and FPG following treatment with saxagliptin 5 mg plus metformin were sustained up to 
Week 102. The HbA1c change for saxagliptin 5 mg plus metformin (n=31) compared to placebo plus 
metformin (n=15) was -0.8% at Week 102.

Saxagliptin add-on to metformin compared with SU add-on to metformin
A 52-week study was conducted to evaluate the efficacy and safety of saxagliptin 5 mg in combination 
with metformin (428 patients) compared with a sulphonylurea (glipizide, 5 mg titrated as needed to 
20 mg, mean dose of 15 mg) in combination with metformin (430 patients) in 858 patients with 
inadequate glycaemic control (HbA1c 6.5%-10%) on metformin alone. The mean metformin dose was 
approximately 1900 mg in each treatment group. After 52 weeks, the saxagliptin and glipizide groups 
had similar mean reductions from baseline in HbA1c in the per-protocol analysis (-0.7% vs. –0.8%, 
respectively, mean baseline HbA1c of 7.5% for both groups). The intent-to-treat analysis showed 
consistent results. The reduction in FPG was slightly less in the saxagliptin-group and there were more 
discontinuations (3.5% vs. 1.2%) due to lack of efficacy based on FPG criteria during the first 
24 weeks of the study. Saxagliptin also resulted in a significantly lower proportion of patients with 
hypoglycaemia, 3% (19 events in 13 subjects) vs. 36.3% (750 events in 156 patients) for glipizide. 
Patients treated with saxagliptin exhibited a significant decrease from baseline in body weight 
compared to a weight gain in patients administered glipizide (-1.1 vs. +1.1 kg).

Saxagliptin add-on to metformin compared with sitagliptin add-on to metformin
An 18-week study was conducted to evaluate the efficacy and safety of saxagliptin 5 mg in 
combination with metformin (403 patients), compared with sitagliptin 100 mg in combination with 
metformin (398 patients) in 801 patients with inadequate glycaemic control on metformin alone. After 
18 weeks, saxagliptin was non-inferior to sitagliptin in mean reduction from baseline in HbA1c in both 
the per-protocol and the full analysis sets. The reductions from baseline in HbA1c respectively for 
saxagliptin and sitagliptin in the primary per-protocol analysis were -0.5% (mean and median) and 



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-0.6% (mean and median). In the confirmatory full analysis set, mean reductions were -0.4% and 
-0.6% respectively for saxagliptin and sitagliptin, with median reductions of -0.5% for both groups.

Saxagliptin in combination with metformin as initial therapy
A 24-week study was conducted to evaluate the efficacy and safety of saxagliptin 5 mg in combination 
with metformin as initial combination therapy in treatment-naïve patients with inadequate glycaemic 
control (HbA1c 8-12%). Initial therapy with the combination of saxagliptin 5 mg plus metformin 
(n=306) provided significant improvements in HbA1c, FPG, and PPG compared to with either 
saxagliptin (n=317) or metformin alone (n=313) as initial therapy. Reductions in HbA1c from baseline 
to Week 24 were observed in all evaluated subgroups defined by baseline HbA1c, with greater 
reductions observed in patients with a baseline HbA1c ≥ 10% (see Table 2). Improvements in HbA1c, 
PPG and FPG following initial therapy with saxagliptin 5 mg plus metformin were sustained up to 
Week 76. The HbA1c change for saxagliptin 5 mg plus metformin (n=177) compared to metformin 
plus placebo (n=147) was -0.5% at Week 76.

Saxagliptin add-on to glibenclamide therapy
An add-on placebo-controlled study of 24-week duration was conducted to evaluate the efficacy and 
safety of saxagliptin in combination with glibenclamide in patients with inadequate glycaemic control 
at enrollment (HbA1c 7.5-10%) on a sub-maximal dose of glibenclamide alone. Saxagliptin in 
combination with a fixed, intermediate dose of a sulphonylurea (glibenclamide 7.5 mg) was compared 
to titration to a higher dose of glibenclamide (approximately 92% of patients in the placebo plus 
glibenclamide group were uptitrated to a final total daily dose of 15 mg). Saxagliptin (n=250) provided 
significant improvements in HbA1c, FPG, and PPG compared to titration to a higher dose of 
glibenclamide (n=264). Improvements in HbA1c and PPG following treatment with saxagliptin 5 mg 
were sustained up to Week 76. The HbA1c change for saxagliptin 5 mg (n=56) compared to uptitrated 
glibenclamide plus placebo (n=27) was -0.7% at Week 76.

Saxagliptin add-on combination therapy with insulin (with or without metformin)
A total of 455 patients with type 2 diabetes participated in a 24-week randomised, double-blind, 
placebo-controlled study to evaluate the efficacy and safety of saxagliptin in combination with a stable 
dose of insulin (baseline mean: 54.2 Units) in patients with inadequate glycaemic control (HbA1c 
≥ 7.5% and ≤ 11%) on insulin alone (n=141) or on insulin in combination with a stable dose of 
metformin (n=314). Saxagliptin 5 mg add-on to insulin with or without metformin provided significant 
improvements after 24 weeks in HbA1c and PPG compared with placebo add-on to insulin with or 
without metformin. Similar HbA1c reductions versus placebo were achieved for patients receiving 
saxagliptin 5 mg add-on to insulin regardless of metformin use (−0.4% for both subgroups). 
Improvements from baseline HbA1c were sustained in the saxagliptin add-on to insulin group 
compared to the placebo add-on to insulin group with or without metformin at Week 52. The HbA1c 
change for the saxagliptin group (n=244) compared to placebo (n=124) was -0.4% at Week 52. 

Saxagliptin add-on to thiazolidinedione therapy
A placebo-controlled study of 24-week duration was conducted to evaluate the efficacy and safety of 
saxagliptin in combination with a thiazolidinedione (TZD) in patients with inadequate glycaemic 
control (HbA1c 7-10.5%) on TZD alone. Saxagliptin (n=183) provided significant improvements in 
HbA1c, FPG, and PPG compared to placebo (n=180). Improvements in HbA1c, PPG and FPG 
following treatment with saxagliptin 5 mg were sustained up to Week 76. The HbA1c change for 
saxagliptin 5 mg (n=82) compared to TZD plus placebo (n=53) was -0.9% at Week 76.

Saxagliptin add-on combination therapy with metformin and sulphonylurea
A total of 257 patients with type 2 diabetes participated in a 24-week randomised, double-blind, 
placebo-controlled study to evaluate the efficacy and safety of saxagliptin (5 mg once daily) in 
combination with metformin plus sulphonylurea (SU) in patients with inadequate glycemic control 
(HbA1c ≥ 7% and ≤ 10%). Saxagliptin (n=127) provided significant improvements in HbA1c and 
PPG compared with the placebo (n=128). The HbA1c change for saxagliptin compared to placebo  
was -0.7% at Week 24.



12

Saxagliptin add-on to dapagliflozin plus metformin therapy
A 24-week randomised, double-blind, placebo-controlled study conducted in patients with type 2 
diabetes mellitus compared saxagliptin 5 mg with placebo as add-on therapy in individuals with 
HbA1c 7-10.5% treated with dapagliflozin (a SGLT2-inhibtor) and metformin. Patients who 
completed the initial 24-week study period were eligible to enter a controlled 28-week long-term study 
extension (52 weeks).

Individuals treated with saxagliptin added to dapagliflozin and metformin (n=153) achieved 
statistically significantly (p-value < 0.0001) greater reductions in HbA1c versus the group with 
placebo added to dapagliflozin plus metformin (n=162) at 24 weeks (see Table 2). The effect on 
HbA1c observed at Week 24 was sustained at Week 52. The safety profile of saxagliptin added to 
dapagliflozin plus metformin in the long-term treatment period was consistent with that observed in 
the 24-week treatment period in this study and in the trial in which saxagliptin and dapagliflozin were 
given concomitantly as add-on therapy to patients treated with metformin (described below).

Proportion of patients achieving HbA1c < 7%
The proportion of patients achieving HbA1c < 7% at Week 24 was higher in the saxagliptin 5 mg plus 
dapagliflozin plus metformin group 35.3% (95% CI [28.2, 42.4]) compared to the placebo plus 
dapagliflozin plus metformin group 23.1% (95% CI [16.9, 29.3]). The effect in HbA1c observed at 
Week 24 was sustained at Week 52.

Table 2 Key efficacy results of Onglyza 5 mg per day in placebo-controlled monotherapy 
trials and in add-on combination therapy trials

Mean 
baseline 
HbA1c 
(%)

Mean change2 from 
baseline HbA1c
(%) at Week 24

Placebo-corrected 
mean change in 
HbA1c (%) at 
Week 24 (95% CI)

MONOTHERAPY STUDIES
 Study CV181011 (n=103) 8.0 -0.5 -0.6 (-0.9, -0.4)3

 Study CV181038 (n=69) 7.9 -0.7 (morning) -0.4 (-0.7, -0.1)4

(n=70) 7.9 -0.6 (evening) -0.4 (-0.6, -0.1)5

ADD-ON/COMBINATION STUDIES

 Study CV181014: add-on to metformin 
(n=186)

8.1 -0.7 -0.8 (-1.0, -0.6)3

 Study CV181040: add-on to SU1

(n=250)
8.5 -0.6 -0.7 (-0.9, -0.6)3

 Study D1680L00006: add-on to 
metformin plus SU (n=257)

8.4 -0.7 -0.7 (-0.9, -0.5)3

 Study CV181013: add-on to TZD 
(n=183)

8.4 -0.9
-0.6 (-0.8, -0.4)3

 Study CV181039: initial combination 
with metformin6

Overall population (n=306)
Baseline HbA1c ≥ 10% stratum 
(n=107)

9.4
10.8

-2.5
-3.3

-0.5 (-0.7, -0.4)7

-0.6 (-0.9, -0.3)8

 Study CV181168: sequential add-on to 
dapagliflozin + metformin (n=315)

7.9 -0.5 -0.4 (-0.5, -0.2)9

 Study CV181057: add-on to insulin 
(+/-metformin)

Overall population (n=300)

8.7 -0.7 -0.4 (-0.6, -0.2)3

n=Randomised patients (primary efficacy-intention-to-treat analysis) with data available.
1 Placebo group had uptitration of glibenclamide from 7.5 to 15 mg total daily dose.
2 Adjusted mean change from baseline adjusted for baseline value (ANCOVA). 
3 p<0.0001 compared to placebo. 
4 p=0.0059 compared to placebo.
5 p=0.0157 compared to placebo.



13

6 Metformin was uptitrated from 500 to 2000 mg per day as tolerated.
7 Mean HbA1c change is the difference between the saxagliptin+metformin and metformin alone groups (p<0.0001).
8 Mean HbA1c change is the difference between the saxagliptin+metformin and metformin alone groups.
9 Mean HbA1c change is the difference between the saxagliptin+dapagliflozin+metformin and dapagliflozin+metformin

groups (p< 0.0001).

Saxagliptin and dapagliflozin add-on to metformin therapy
A total of 534 adult patients with type 2 diabetes mellitus and inadequate glycaemic control on 
metformin alone (HbA1c 8%-12%), participated in this 24-week randomised, double-blind, active 
comparator-controlled trial to compare the combination of saxagliptin and dapagliflozin added 
concurrently to metformin, versus saxagliptin or dapagliflozin added to metformin. Patients were 
randomised to one of three double-blind treatment groups to receive saxagliptin 5 mg and 
dapagliflozin 10 mg added to metformin, saxagliptin 5 mg and placebo added to metformin, or 
dapagliflozin 10 mg and placebo added to metformin.

The saxagliptin and dapagliflozin group achieved significantly greater reductions in HbA1c versus 
either the saxagliptin group or dapagliflozin group at 24 weeks (see Table 3).

Table 3 HbA1c at Week 24 in active-controlled study comparing the combination of 
saxagliptin and dapagliflozin added concurrently to metformin with either 
saxagliptin or dapagliflozin added to metformin

Efficacy parameter

Saxagliptin 5 mg
+ dapagliflozin 

10 mg 
+ metformin

N=1792

Saxagliptin 5 mg 
+ metformin

N=1762

Dapagliflozin 
10 mg

+ metformin
N=1792

HbA1c (%) at week 241

Baseline (mean) 8.93 9.03 8.87

Change from baseline (adjusted 
mean3)
(95% Confidence interval [CI])

−1.47
(−1.62, −1.31)

−0.88
(−1.03, −0.72)

−1.20
(−1.35, −1.04)

Difference from saxagliptin + 
metformin (adjusted mean3)
(95% CI)

−0.594

(−0.81, −0.37) - -

Difference from dapagliflozin + 
metformin (adjusted mean3)
(95% CI)

−0.275

(−0.48, −0.05) - -

1 LRM = Longitudinal repeated measures (using values prior to rescue).
2 Randomised and treated patients with baseline and at least 1 post baseline efficacy measurement.
3 Least squares mean adjusted for baseline value.
4 p-value < 0.0001.
5 p-value=0.0166.

Proportion of patients achieving HbA1c < 7%
In the saxagliptin and dapagliflozin combination group, 41.4% (95% CI [34.5, 48.2]) of patients
achieved HbA1c levels of less than 7% compared to 18.3% (95% CI [13.0, 23.5]) of patients in the 
saxagliptin group and 22.2% (95% CI [16.1, 28.3]) of patients in the dapagliflozin group.

Patients with renal impairment
A 12-week, multi-centre, randomised, double-blind, placebo-controlled study was conducted to 
evaluate the treatment effect of saxagliptin 2.5 mg once daily compared with placebo in 170 patients 
(85 patients on saxagliptin and 85 on placebo) with type 2 diabetes (HbA1c 7.0-11%) and renal 
impairment (moderate [n=90]; severe [n=41]; or ESRD [n=39]). In this study, 98.2% of the patients 
received other antihyperglycaemic treatments (75.3% on insulin and 31.2% on oral 
antihyperglycaemics; some received both). Saxagliptin significantly decreased HbA1c compared with 



14

placebo; the HbA1c change for saxagliptin was -0.9% at Week 12 (HbA1c change of -0.4% for 
placebo). Improvements in HbA1c following treatment with saxagliptin 2.5 mg were sustained up to 
Week 52, however, the number of patients who completed 52 weeks without modification of other 
antihyperglycaemic treatment was low (26 subjects in the saxagliptin group versus 34 subjects in the 
placebo group). The incidence of confirmed hypoglycaemic events was somewhat higher in the 
saxagliptin group (9.4%) versus placebo group (4.7%) although the number of subjects with any 
hypoglycaemic event did not differ between the treatment groups. There was no adverse effect on 
renal function as determined by estimated glomerular filtration rate or CrCL at Week 12 and Week 52.

Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus -
Thrombolysis in Myocardial Infarction (SAVOR) Study
SAVOR was a CV outcome trial in 16,492 patients with HbA1c ≥6.5% and <12% (12959 with 
established CV disease; 3533 with multiple risk factors only) who were randomised to saxagliptin 
(n=8280) or placebo (n=8212) added to regional standards of care for HbA1c and CV risk factors. The 
study population included those ≥65 years (n=8561) and ≥75 years (n=2330), with normal or mild 
renal impairment (n=13,916) as well as moderate (n=2240) or severe (n=336) renal impairment.

The primary safety (noninferiority) and efficacy (superiority) endpoint was a composite endpoint 
consisting of the time-to-first occurrence of any of the following major adverse CV events (MACE): 
CV death, nonfatal myocardial infarction, or nonfatal ischaemic stroke.

After a mean follow up of 2 years, the trial met its primary safety endpoint demonstrating saxagliptin 
does not increase the cardiovascular risk in patients with type 2 diabetes compared to placebo when 
added to current background therapy.

No benefit was observed for MACE or all-cause mortality.

Table 4 Primary and Secondary Clinical Endpoints by Treatment Group in the SAVOR 
Study*

Endpoint

Saxagliptin
(N=8280)

Placebo
(N=8212)

Hazard 
Ratio 

(95% CI)†

Subjects with 
events
n (%)

Event rate 
per 100 

patient-yrs

Subjects 
with events

n (%)
Event rate per 
100 patient-yrs

Primary composite 
endpoint: MACE

613
(7.4)

3.76 609
(7.4)

3.77 1.00
(0.89, 1.12)‡,§, #

Secondary composite 
endpoint: MACE plus

1059
(12.8)

6.72 1034
(12.6)

6.60 1.02
(0.94, 1.11)¶

All-cause mortality 420
(5.1)

2.50 378
(4.6)

2.26 1.11
(0.96, 1.27)¶

* Intent-to-treat population
† Hazard ratio adjusted for baseline renal function category and baseline CVD risk category.
‡ p-value <0.001 for noninferiority (based on HR <1.3) compared to placebo.
§ p-value = 0.99 for superiority (based on HR <1.0) compared to placebo.
# Events accumulated consistently over time, and the event rates for Onglyza and placebo did not diverge notably over 

time.
¶ Significance not tested.

One component of the secondary composite endpoint, hospitalisation for heart failure, occurred at a 
greater rate in the saxagliptin group (3.5%) compared with the placebo group (2.8%), with nominal 
statistical significance favouring placebo [HR = 1.27; (95% CI 1.07, 1.51); P = 0.007]. Clinically 
relevant factors predictive of increased relative risk with saxagliptin treatment could not be 
definitively identified. Subjects at higher risk for hospitalisation for heart failure, irrespective of 
treatment assignment, could be identified by known risk factors for heart failure such as baseline 
history of heart failure or impaired renal function. However, subjects on saxagliptin with a history of 
heart failure or impaired renal function at baseline were not at an increased risk relative to placebo for 
the primary or secondary composite endpoints or all-cause mortality.



15

Another secondary endpoint, all-cause mortality, occurred at a rate of 5.1% in the saxagliptin group 
and 4.6% in the placebo group (see Table 4). CV deaths were balanced across the treatment groups. 
There was a numerical imbalance in non-CV death, with more events on saxagliptin (1.8%) than 
placebo (1.4%) [HR = 1.27; (95% CI 1.00, 1.62); P = 0.051].

A1C was lower with saxagliptin compared to placebo in an exploratory analysis.

Paediatric population
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Onglyza in one or more subsets of the paediatric population in the treatment of type 2 diabetes 
mellitus (see section 4.2 for information on paediatric use).

Elderly population 
In the SAVOR study subgroups over 65 and over 75 years of age, efficacy and safety were consistent 
with the overall study population. 

GENERATION was a 52-week glycaemic control study in 720 elderly patients, the mean age was 
72.6 years; 433 subjects (60.1%) were < 75 years of age, and 287 subjects (39.9%) were ≥ 75 years of 
age. Primary endpoint was the proportion of patients reaching HbA1c < 7% without confirmed or 
severe hypoglycaemia. There appeared to be no difference in percentage responders: 37.9% 
(saxagliptin) and 38.2% (glimepiride) achieved the primary endpoint. A lower proportion of patients 
in the saxagliptin group (44.7%) compared to the glimepiride group (54.7%) achieved an HbA1c 
target of 7.0%. A lower proportion of patients in the saxagliptin group (1.1%) compared to the
glimepiride group (15.3%) experienced a confirmed or severe hypoglycaemic event.

5.2 Pharmacokinetic properties

The pharmacokinetics of saxagliptin and its major metabolite were similar in healthy subjects and in 
patients with type 2 diabetes.

Absorption
Saxagliptin was rapidly absorbed after oral administration in the fasted state, with maximum plasma 
concentrations (Cmax) of saxagliptin and its major metabolite attained within 2 and 4 hours (Tmax), 
respectively. The Cmax and AUC values of saxagliptin and its major metabolite increased 
proportionally with the increment in the saxagliptin dose, and this dose-proportionality was observed 
in doses up to 400 mg. Following a 5 mg single oral dose of saxagliptin to healthy subjects, the mean 
plasma AUC values for saxagliptin and its major metabolite were 78 ng·h/ml and 214 ng·h/ml, 
respectively. The corresponding plasma Cmax values were 24 ng/ml and 47 ng/ml, respectively. The 
intra-subject coefficients of variation for saxagliptin Cmax and AUC were less than 12%.

The inhibition of plasma DPP4 activity by saxagliptin for at least 24 hours after oral administration of 
saxagliptin is due to high potency, high affinity, and extended binding to the active site.

Interaction with food
Food had relatively modest effects on the pharmacokinetics of saxagliptin in healthy subjects. 
Administration with food (a high-fat meal) resulted in no change in saxagliptin Cmax and a 27% 
increase in AUC compared with the fasted state. The time for saxagliptin to reach Cmax (Tmax) was 
increased by approximately 0.5 hours with food compared with the fasted state. These changes were 
not considered to be clinically meaningful.

Distribution
The in vitro protein binding of saxagliptin and its major metabolite in human serum is negligible. 
Thus, changes in blood protein levels in various disease states (e.g. renal or hepatic impairment) are
not expected to alter the disposition of saxagliptin.



16

Biotransformation
The biotransformation of saxagliptin is primarily mediated by cytochrome P450 3A4/5 (CYP3A4/5). 
The major metabolite of saxagliptin is also a selective, reversible, competitive DPP4 inhibitor, half as 
potent as saxagliptin.

Elimination
The mean plasma terminal half-life (t1/2) values for saxagliptin and its major metabolite are 2.5 hours 
and 3.1 hours respectively, and the mean t1/2 value for plasma DPP4 inhibition was 26.9 hours. 
Saxagliptin is eliminated by both renal and hepatic pathways. Following a single 50 mg dose of 
14C-saxagliptin, 24%, 36%, and 75% of the dose was excreted in the urine as saxagliptin, its major 
metabolite, and total radioactivity respectively. The average renal clearance of saxagliptin 
(~230 ml/min) was greater than the average estimated glomerular filtration rate (~120 ml/min), 
suggesting some active renal excretion. For the major metabolite, renal clearance values were 
comparable to estimated glomerular filtration rate. A total of 22% of the administered radioactivity 
was recovered in faeces representing the fraction of the saxagliptin dose excreted in bile and/or 
unabsorbed medicinal product from the gastrointestinal tract.

Linearity
The Cmax and AUC of saxagliptin and its major metabolite increased proportionally to the saxagliptin 
dose. No appreciable accumulation of either saxagliptin or its major metabolite was observed with 
repeated once-daily dosing at any dose level. No dose- and time-dependence was observed in the 
clearance of saxagliptin and its major metabolite over 14 days of once-daily dosing with saxagliptin at 
doses ranging from 2.5 mg to 400 mg.

Special populations
Renal impairment
A single-dose, open-label study was conducted to evaluate the pharmacokinetics of a 10 mg oral dose 
of saxagliptin in subjects with varying degrees of chronic renal impairment compared to subjects with 
normal renal function. The study included patients with renal impairment classified on the basis of 
creatinine clearance as mild (approximately GFR ≥ 45 to < 90 mL/min), moderate (approximately
GFR ≥ 30 to < 45 mL/min), or severe (approximately GFR < 30 mL/min), as well as patients with 
ESRD on haemodialysis. 

The degree of renal impairment did not affect the Cmax of saxagliptin or its major metabolite. In 
subjects with mild renal impairment, the mean AUC values of saxagliptin and its major metabolite 
were 1.2- and 1.7- fold higher, respectively, than mean AUC values in subjects with normal renal 
function. Because increases of this magnitude are not clinically relevant, dose adjustment in patients 
with mild renal impairment is not recommended. In subjects with moderate or severe renal impairment 
or in subjects with ESRD on haemodialysis, the AUC values of saxagliptin and its major metabolite 
were up to 2.1- and 4.5-fold higher, respectively, than AUC values in subjects with normal renal 
function.

Hepatic impairment
In subjects with mild (Child-Pugh Class A), moderate (Child-Pugh Class B), or severe (Child-Pugh 
Class C) hepatic impairment the exposures to saxagliptin were 1.1-, 1.4- and 1.8-fold higher, 
respectively, and the exposures to BMS-510849 were 22%, 7% and 33% lower, respectively, than 
those observed in healthy subjects.

Elderly (≥ 65 years)
Elderly patients (65-80 years) had about 60% higher saxagliptin AUC than young patients 
(18-40 years). This is not considered clinically meaningful, therefore, no dose adjustment for Onglyza 
is recommended on the basis of age alone.

5.3 Preclinical safety data

In cynomolgus monkeys saxagliptin produced reversible skin lesions (scabs, ulcerations and necrosis) 
in extremities (tail, digits, scrotum and/or nose) at doses ≥ 3 mg/kg/day. The no effect level (NOEL) 



17

for the lesions is 1- and 2-times the human exposure of saxagliptin and the major metabolite 
respectively, at the recommended human dose of 5 mg/day (RHD).

The clinical relevance of the skin lesions is not known, however, clinical correlates to skin lesions in 
monkeys have not been observed in human clinical trials of saxagliptin.

Immune related findings of minimal, nonprogressive, lymphoid hyperplasia in spleen, lymph nodes 
and bone marrow with no adverse sequelae have been reported in all species tested at exposures 
starting from 7-times the RHD.

Saxagliptin produced gastrointestinal toxicity in dogs, including bloody/mucoid faeces and 
enteropathy at higher doses with a NOEL 4- and 2-times the human exposure for saxagliptin and the 
major metabolite, respectively, at RHD.

Saxagliptin was not genotoxic in a conventional battery of genotoxicity studies in vitro and in vivo. No 
carcinogenic potential was observed in two-year carcinogenicity assays with mice and rats.

Effects on fertility were observed in male and female rats at high doses producing overt signs of 
toxicity. Saxagliptin was not teratogenic at any doses evaluated in rats or rabbits. At high doses in rats, 
saxagliptin caused reduced ossification (a developmental delay) of the foetal pelvis and decreased 
foetal body weight (in the presence of maternal toxicity), with a NOEL 303- and 30-times the human 
exposure for saxagliptin and the major metabolite, respectively, at RHD. In rabbits, the effects of 
saxagliptin were limited to minor skeletal variations observed only at maternally toxic doses (NOEL 
158- and 224-times the human exposure for saxagliptin and the major metabolite, respectively at 
RHD). In a pre- and postnatal developmental study in rats, saxagliptin caused decreased pup weight at 
maternally toxic doses, with NOEL 488- and 45-times the human exposure for saxagliptin and the 
major metabolite, respectively at RHD. The effect on offspring body weights were noted until 
postnatal day 92 and 120 in females and males, respectively.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core
Lactose monohydrate
Cellulose, microcrystalline (E460i)
Croscarmellose sodium (E468)
Magnesium stearate

Film-coating
Onglyza 2.5 mg film-coated tablets
Polyvinyl alcohol
Macrogol 3350
Titanium dioxide (E171)
Talc (E553b)
Iron oxide yellow (E172)

Onglyza 5 mg film-coated tablets
Polyvinyl alcohol
Macrogol 3350
Titanium dioxide (E171)
Talc (E553b)
Iron oxide red (E172)

Printing ink
Shellac



18

Indigo carmine aluminium lake (E132)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Alu/Alu blister.

Onglyza 2.5 mg film-coated tablets
Pack sizes of 14, 28, and 98 film-coated tablets in non-perforated calendar blisters.
Pack sizes of 30x1 and 90x1 film-coated tablets in perforated unit dose blisters.
Not all pack sizes may be marketed.

Onglyza 5 mg film-coated tablets
Pack sizes of 14, 28, 56 and 98 film-coated tablets in non-perforated blisters.
Pack sizes of 14, 28, 56 and 98 film-coated tablets in non-perforated calendar blisters.
Pack sizes of 30x1 and 90x1 film-coated tablets in perforated unit dose blisters.
Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

7. MARKETING AUTHORISATION HOLDER

AstraZeneca AB
SE-151 85 Södertälje
Sweden

8. MARKETING AUTHORISATION NUMBER(S)

Onglyza 2.5 mg film-coated tablets
EU/1/09/545/011-015

Onglyza 5 mg film-coated tablets
EU/1/09/545/001-010

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 01 October 2009
Date of latest renewal: 18 July 2014



19

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/


20

ANNEX II

A. 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



21

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer(s) responsible for batch release

AstraZeneca GmbH
Tinsdaler Weg 183
22880 Wedel
Germany

AstraZeneca UK Limited
Silk Road Business Park
Macclesfield
Cheshire
SK10 2NA
United Kingdom

Bristol-Myers Squibb Company
Contrada Fontana del Ceraso
IT-03012 Anagni (FR)
Italy

The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch.

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 (RMP)

The MAH shall perform the required pharmacovigilance activities and interventions detailed in 
the agreed 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.



22

ANNEX III

LABELLING AND PACKAGE LEAFLET



23

A. LABELLING



24

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Onglyza 2.5 mg film-coated tablets
saxagliptin

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each film-coated tablet contains 2.5 mg saxagliptin (as hydrochloride).

3. LIST OF EXCIPIENTS

Contains lactose. See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

14 film-coated tablets
28 film-coated tablets
30x1 film-coated tablets
90x1 film-coated tablets
98 film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use

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 WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS



25

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

AstraZeneca AB
SE-151 85 Södertälje
Sweden

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/09/545/011
EU/1/09/545/012
EU/1/09/545/013
EU/1/09/545/014
EU/1/09/545/015

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

onglyza 2.5 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC
SN
NN



26

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTERS (PERFORATED/NON-PERFORATED) 

1. NAME OF THE MEDICINAL PRODUCT

Onglyza 2.5 mg tablets
saxagliptin

2. NAME OF THE MARKETING AUTHORISATION HOLDER

AstraZeneca AB

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



27

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

CALENDAR BLISTERS (NON-PERFORATED) 

1. NAME OF THE MEDICINAL PRODUCT

Onglyza 2.5 mg tablets
saxagliptin

2. NAME OF THE MARKETING AUTHORISATION HOLDER

AstraZeneca AB

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

Monday Tuesday Wednesday Thursday Friday Saturday Sunday



28

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Onglyza 5 mg film-coated tablets
saxagliptin

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each film-coated tablet contains 5 mg saxagliptin (as hydrochloride).

3. LIST OF EXCIPIENTS

Contains lactose. See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

14 film-coated tablets
28 film-coated tablets
30x1 film-coated tablets
56 film-coated tablets
90x1 film-coated tablets
98 film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use

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 WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS



29

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

AstraZeneca AB
SE-151 85 Södertälje
Sweden

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/09/545/001
EU/1/09/545/002
EU/1/09/545/003
EU/1/09/545/004
EU/1/09/545/005
EU/1/09/545/006
EU/1/09/545/007
EU/1/09/545/008
EU/1/09/545/009
EU/1/09/545/010

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

onglyza 5 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC
SN
NN



30

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

BLISTERS (PERFORATED/NON-PERFORATED)

1. NAME OF THE MEDICINAL PRODUCT

Onglyza 5 mg tablets
saxagliptin

2. NAME OF THE MARKETING AUTHORISATION HOLDER

AstraZeneca AB

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



31

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

CALENDAR BLISTERS (NON-PERFORATED) 

1. NAME OF THE MEDICINAL PRODUCT

Onglyza 5 mg tablets
saxagliptin

2. NAME OF THE MARKETING AUTHORISATION HOLDER

AstraZeneca AB

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

Monday Tuesday Wednesday Thursday Friday Saturday Sunday



32

B. PACKAGE LEAFLET



33

Package leaflet: Information for the patient

Onglyza 2.5 mg film-coated tablets
Saxagliptin

Read all of this leaflet carefully before you start taking 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 Onglyza is and what it is used for
2. What you need to know before you take Onglyza
3. How to take Onglyza
4. Possible side effects
5. How to store Onglyza
6. Contents of the pack and other information

1. What Onglyza is and what it is used for

Onglyza contains the active substance saxagliptin, which belongs to a group of medicines called ‘oral 
anti-diabetics’. They work by helping to control the level of sugar in your blood.

Onglyza is used for adult patients aged 18 years and older with ‘type 2 diabetes’, if the disease cannot 
be adequately controlled with one oral anti-diabetic medicine, diet and exercise. Onglyza is used alone 
or together with insulin or other anti-diabetic medicines.

It is important to keep following the advice about diet and exercise that you have been given by your 
doctor or nurse.

2. What you need to know before you take Onglyza

Do not take Onglyza
 if you are allergic to saxagliptin or any of the other ingredients of this medicine (listed in 

section 6).
 if you have had a serious allergic reaction to any other similar medicines that you take to control 

your blood sugar. See section 4.

Warnings and precautions:
Talk to your doctor or pharmacist before taking Onglyza:
 if you are taking insulin. Onglyza should not be used in place of insulin;
 if you have type 1 diabetes (your body does not produce any insulin) or diabetic ketoacidosis (a 

complication of diabetes with high blood sugar, rapid weight loss, nausea or vomiting). Onglyza 
should not be used to treat these conditions;

 if you have or have had a disease of the pancreas;



34

 if you are taking insulin or an anti-diabetic medicine known as ‘sulphonylurea’, your doctor 
may want to reduce your dose of insulin or the sulphonylurea when you take either of them 
together with Onglyza in order to avoid low blood sugar;

 if you have a condition that reduces your defence against infections, such as a disease like 
AIDS, or from medicines that you might take after an organ transplant;

 if you suffer from heart failure or you have other risk factors for developing heart failure such as 
problems with your kidneys. Your doctor will advise you of the signs and symptoms of heart 
failure. You should call your doctor, pharmacist or nurse immediately if you experience any of 
these symptoms. Symptoms can include, but are not limited to, increasing shortness of breath, 
rapid increase in weight and swelling of the feet (pedal oedema);

 if you have reduced kidney function, your doctor will decide if you need to take a lower dose of 
Onglyza. If you are having haemodialysis then Onglyza is not recommended for you;

 if you have moderate or severe liver problems. If you have severe liver problems, then Onglyza 
is not recommended for you.

Diabetic skin lesions are a common complication of diabetes. Rash has been seen with Onglyza (see 
section 4) and with certain anti-diabetic medicines in the same class as Onglyza. You are advised to 
follow the recommendations for skin and foot care that you are given by your doctor or nurse. Contact 
your doctor if you encounter blistering of the skin, as it may be a sign for a condition called bullous 
pemphigoid. Your doctor may ask you to stop Onglyza.

Children and adolescents
Onglyza is not recommended for children and adolescents under 18 years. It is not known if this 
medicine is safe and effective when used in children and adolescents under 18 years of age.

Other medicines and Onglyza
Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 

In particular, you should tell your doctor if you are using medicines containing any of the following 
active substances:
 Carbamazepine, phenobarbital or phenytoin. These may be used to control fits (seizures) or 

chronic pain.
 Dexamethasone – a steroid medicine. This may be used to treat inflammation in different body 

parts and organs.
 Rifampicin. This is an antibiotic used to treat infections such as tuberculosis.
 Ketoconazole. This may be used to treat fungal infections.
 Diltiazem. This is a medicine used to lower blood pressure.

Pregnancy and breast-feeding
Talk to your doctor before you take Onglyza if you are pregnant or plan to become pregnant. You 
should not use Onglyza if you are pregnant.

Talk to your doctor if you want to breast-feed while taking this medicine. It is not known if Onglyza 
passes into human breast milk. You should not take this medicine if you are breast-feeding or plan to 
breast-feed.

Driving and using machines
If you feel dizzy while taking Onglyza, do not drive or use any tools or machines. Hypoglycaemia 
may affect your ability to drive and use machines or work with safe foothold and there is a risk of 
hypoglycaemia when taking this medicine in combination with medicines known to cause 
hypoglycaemia such as insulin and sulphonylureas.

Onglyza contains lactose
The tablets contain lactose (milk sugar). If you have been told by your doctor that you have an 
intolerance to some sugars, contact your doctor before taking this medicine.



35

Sodium content
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say it is essentially 
‘sodium-free’.

3. How to take Onglyza

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure.

The recommended dose of Onglyza is 5 mg once a day.

If you have reduced kidney function, your doctor may prescribe a lower dose. This is one 2.5 mg tablet 
once a day.

Your doctor may prescribe Onglyza alone or together with insulin or other anti-diabetic medicines. If 
applicable, remember to take these other medicines as directed by your doctor to achieve the best 
results for your health.

How to take Onglyza
The tablets must not be split or cut. Swallow the tablet whole with some water. You can take the tablet 
with or without food. The tablet can be taken at any time of the day, however, try to take your tablet at 
the same time each day. This will help you to remember to take it.

If you take more Onglyza than you should
If you take more tablets than you should, talk to a doctor straight away.

If you forget to take Onglyza
 If you forget to take a dose of Onglyza, take it as soon as you remember it. However, if it is 

nearly time for the next dose, skip the missed dose. 
 Do not take a double dose to make up for a forgotten dose. Never take two doses on the same 

day.

If you stop taking Onglyza
Keep taking Onglyza until your doctor tells you to stop. This is to help keep your blood sugar under 
control.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Some symptoms need immediate medical attention:
You should stop taking Onglyza and see your doctor immediately if you experience the following 
symptoms of low blood sugar: trembling, sweating, anxiety, blurred vision, tingling lips, paleness, 
mood change, vagueness or confusion (hypoglycaemia); seen very commonly (may affect more than 1 
in 10 people).

Symptoms of a serious allergic reaction (seen rarely, may affect up to 1 in 1,000 people) may include:
o Rash
o Raised red patches on your skin (hives)
o Swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or 

swallowing.



36

If you have these symptoms, stop taking Onglyza and call your doctor or nurse right away. Your 
doctor may prescribe a medicine to treat your allergic reaction and a different medicine for your 
diabetes.

You should stop taking Onglyza 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).

You should call your doctor if you experience the following side effect:
 Severe joint pain.

Some patients have had the following side effects while taking Onglyza and metformin:
 Common (may affect 1 to 10 users in 100): infection of the upper chest or lungs, infection of the 

urinary tract, inflamed stomach or gut usually caused by an infection (gastroenteritis), infection 
of the sinuses with a feeling of pain and fullness behind your cheeks and eyes (sinusitis), 
inflamed nose or throat (nasopharyngitis) (signs of this may include a cold or a sore throat), 
headache, muscle pain (myalgia), vomiting, inflammation of the stomach (gastritis), stomach 
ache and indigestion (dyspepsia).

 Uncommon (may affect 1 to 10 users in 1,000): joint pain (arthralgia) and difficulties in getting 
or maintaining an erection (erectile dysfunction).

Some patients have had the following side effects while taking Onglyza and a sulphonylurea:
 Very common: low blood sugar (hypoglycaemia)
 Common: infection of the upper chest or lungs, infection of the urinary tract, inflamed stomach 

or gut usually caused by an infection (gastroenteritis), infection of the sinuses with a feeling of 
pain and fullness behind your cheeks and eyes (sinusitis), headache, stomach ache and vomiting.

 Uncommon: tiredness, abnormal lipid (fatty acids) levels (dyslipidaemia, 
hypertriglyceridaemia).

Some patients have had the following side effects while taking Onglyza and a thiazolidinedione:
 Common: infection of the upper chest or lungs, infection of the urinary tract, inflamed stomach 

or gut usually caused by an infection (gastroenteritis), infection of the sinuses with a feeling of 
pain and fullness behind your cheeks and eyes (sinusitis), headache, vomiting, stomach ache and 
swelling of the hands, ankles or feet (peripheral oedema).

Some patients have had the following side effects while taking Onglyza and metformin and a 
sulphonylurea:
 Common: dizziness, tiredness, stomach ache and flatulence.

Some patients have had the following additional side effects while taking Onglyza alone: 
 Common: dizziness, diarrhoea and stomach ache.

Some patients have had the following side effects while taking Onglyza alone or in combination:
 Not known (frequency cannot be estimated from the available data): constipation, blistering of 

the skin (bullous pemphigoid)

Some patients have had a small reduction in the number of one type of white blood cells (lymphocytes) 
shown in a blood test when Onglyza was used alone or in combination.

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 



37

system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Onglyza

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 blister and the carton after EXP. 
The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not use this medicine if the package is damaged or shows signs of tampering.

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 to protect the environment.

6. Contents of the pack and other information

What Onglyza contains
- The active substance is saxagliptin. Each film-coated tablet contains 2.5 mg saxagliptin (as 

hydrochloride).

- The other ingredients are:
 Tablet core: lactose monohydrate; cellulose, microcrystalline (E460i); croscarmellose sodium 

(E468); magnesium stearate.
 Film-coating: polyvinyl alcohol; macrogol 3350; titanium dioxide (E171); talc (E553b) and 

iron oxide yellow (E172).
Printing ink: shellac; indigo carmine aluminium lake (E132).

What Onglyza looks like and contents of the pack

 2.5 mg film-coated tablets are pale yellow to light yellow, biconvex, round. They have “2.5” 
printed on one side and “4214” printed on the other side, in blue ink.

 Tablets available in aluminium foil blisters. 
 2.5 mg tablets are available in pack sizes of 14, 28, or 98 film-coated tablets in non-perforated 

calendar blisters and 30x1 or 90x1 film-coated tablets in perforated unit dose blisters.

Not all pack sizes may be marketed in your country.

Marketing Authorisation Holder 

AstraZeneca AB
SE-151 85 Södertälje
Sweden

Manufacturer:

AstraZeneca GmbH
Tinsdaler Weg 183
22880 Wedel
Germany

AstraZeneca UK Limited
Silk Road Business Park

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


38

Macclesfield
Cheshire
SK10 2NA
United Kingdom

Bristol-Myers Squibb Company
Contrada Fontana del Ceraso 
IT-03012 Anagni (FR)
Italy

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

België/Belgique/Belgien
AstraZeneca S.A./N.V.
Tel: +32 2 370 48 11

Lietuva
UAB AstraZeneca Lietuva
Tel: +370 5 2660550

България
АстраЗенека България ЕООД
Тел.: +359 (2) 44 55 000

Luxembourg/Luxemburg
AstraZeneca S.A./N.V.
Tél/Tel: +32 2 370 48 11

Česká republika
AstraZeneca Czech Republic s.r.o.
Tel: +420 222 807 111

Magyarország
AstraZeneca Kft.
Tel.: +36 1 883 6500

Danmark
AstraZeneca A/S
Tlf: +45 43 66 64 62

Malta
Associated Drug Co. Ltd
Tel: +356 2277 8000

Deutschland
AstraZeneca GmbH
Tel: +49 41 03 7080

Nederland
AstraZeneca BV
Tel: +31 79 363 2222

Eesti
AstraZeneca 
Tel: +372 6549 600

Norge
AstraZeneca AS
Tlf: +47 21 00 64 00

Ελλάδα
AstraZeneca A.E.
Τηλ: +30 2 106871500

Österreich
AstraZeneca Österreich GmbH
Tel: +43 1 711 31 0

España
AstraZeneca Farmacéutica Spain, S.A.
Tel: +34 91 301 91 00

Polska
AstraZeneca Pharma Poland Sp. z o.o.
Tel.: +48 22 245 73 00

France
AstraZeneca
Tél: +33 1 41 29 40 00

Portugal
AstraZeneca Produtos Farmacêuticos, Lda.
Tel: +351 21 434 61 00

Hrvatska 
AstraZeneca d.o.o.
Tel: +385 1 4628 000

România
AstraZeneca Pharma SRL
Tel: +40 21 317 60 41

Ireland
AstraZeneca Pharmaceuticals (Ireland) DAC
Tel: +353 1609 7100

Slovenija
AstraZeneca UK Limited
Tel: +386 1 51 35 600



39

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
AstraZeneca AB, o.z.
Tel: +421 2 5737 7777

Italia
AstraZeneca S.p.A.
Tel: +39 02 9801 1

Suomi/Finland
AstraZeneca Oy
Puh/Tel: +358 10 23 010

Κύπρος
Αλέκτωρ Φαρµακευτική Λτδ
Τηλ: +357 22490305

Sverige
AstraZeneca AB
Tel: +46 8 553 26 000

Latvija
SIA AstraZeneca Latvija
Tel: +371 67377100

United Kingdom
AstraZeneca UK Ltd
Tel: +44 1582 836 836

This leaflet was last revised in 

Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu.

http://www.emea.europa.eu/
http://www.emea.europa.eu/


40

Package leaflet: Information for the patient

Onglyza 5 mg film-coated tablets
Saxagliptin

Read all of this leaflet carefully before you start taking 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 Onglyza is and what it is used for
2. What you need to know before you take Onglyza
3. How to take Onglyza
4. Possible side effects
5. How to store Onglyza
6. Contents of the pack and other information

1. What Onglyza is and what it is used for

Onglyza contains the active substance saxagliptin, which belongs to a group of medicines called ‘oral 
anti-diabetics’. They work by helping to control the level of sugar in your blood.

Onglyza is used for adult patients aged 18 years and older with ‘type 2 diabetes’, if the disease cannot 
be adequately controlled with one oral anti-diabetic medicine, diet and exercise. Onglyza is used alone 
or together with insulin or other anti-diabetic medicines.

It is important to keep following the advice about diet and exercise that you have been given by your 
doctor or nurse.

2. What you need to know before you take Onglyza

Do not take Onglyza
 if you are allergic to saxagliptin or any of the other ingredients of this medicine (listed in 

section 6).
 if you have had a serious allergic reaction to any other similar medicines that you take to control 

your blood sugar. See section 4.

Warnings and precautions:
Talk to your doctor or pharmacist before taking Onglyza:
 if you are taking insulin. Onglyza should not be used in place of insulin;
 if you have type 1 diabetes (your body does not produce any insulin) or diabetic ketoacidosis (a 

complication of diabetes with high blood sugar, rapid weight loss, nausea or vomiting). Onglyza 
should not be used to treat these conditions;

 if you have or have had a disease of the pancreas;



41

 if you are taking insulin or an anti-diabetic medicine known as ‘sulphonylurea’, your doctor 
may want to reduce your dose of insulin or the sulphonylurea when you take either of them 
together with Onglyza in order to avoid low blood sugar;

 if you have a condition that reduces your defence against infections, such as a disease like 
AIDS, or from medicines that you might take after an organ transplant;

 if you suffer from heart failure or you have other risk factors for developing heart failure such as 
problems with your kidneys. Your doctor will advise you of the signs and symptoms of heart 
failure. You should call your doctor, pharmacist or nurse immediately if you experience any of 
these symptoms. Symptoms can include, but are not limited to, increasing shortness of breath, 
rapid increase in weight and swelling of the feet (pedal oedema);

 if you have reduced kidney function, your doctor will decide if you need to take a lower dose of 
Onglyza. If you are having haemodialysis then Onglyza is not recommended for you;

 if you have moderate or severe liver problems. If you have severe liver problems, then Onglyza 
is not recommended for you.

Diabetic skin lesions are a common complication of diabetes. Rash has been seen with Onglyza (see 
section 4) and with certain anti-diabetic medicines in the same class as Onglyza. You are advised to 
follow the recommendations for skin and foot care that you are given by your doctor or nurse. Contact 
your doctor if you encounter blistering of the skin, as it may be a sign for a condition called bullous 
pemphigoid. Your doctor may ask you to stop Onglyza.

Children and adolescents
Onglyza is not recommended for children and adolescents under 18 years. It is not known if this 
medicine is safe and effective when used in children and adolescents under 18 years of age.

Other medicines and Onglyza
Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 

In particular, you should tell your doctor if you are using medicines containing any of the following 
active substances:
 Carbamazepine, phenobarbital or phenytoin. These may be used to control fits (seizures) or 

chronic pain.
 Dexamethasone – a steroid medicine. This may be used to treat inflammation in different body 

parts and organs.
 Rifampicin. This is an antibiotic used to treat infections such as tuberculosis.
 Ketoconazole. This may be used to treat fungal infections.
 Diltiazem. This is a medicine used to lower blood pressure.

Pregnancy and breast-feeding
Talk to your doctor before you take Onglyza if you are pregnant or plan to become pregnant. You 
should not use Onglyza if you are pregnant.

Talk to your doctor if you want to breast-feed while taking this medicine. It is not known if Onglyza 
passes into human breast milk. You should not take this medicine if you are breast-feeding or plan to 
breast-feed.

Driving and using machines
If you feel dizzy while taking Onglyza, do not drive or use any tools or machines. Hypoglycaemia 
may affect your ability to drive and use machines or work with safe foothold and there is a risk of 
hypoglycaemia when taking this medicine in combination with medicines known to cause 
hypoglycaemia such as insulin and sulphonylureas.

Onglyza contains lactose
The tablets contain lactose (milk sugar). If you have been told by your doctor that you have an 
intolerance to some sugars, contact your doctor before taking this medicine.



42

Sodium content
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say it is essentially 
‘sodium-free’.

3. How to take Onglyza

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure.

The recommended dose of Onglyza is one 5 mg tablet once a day.

If you have reduced kidney function, your doctor may prescribe a lower dose. This is one 2.5 mg tablet 
once a day. For this dose, a different tablet strength is available.

Your doctor may prescribe Onglyza alone or together with insulin or other anti-diabetic medicines. If 
applicable, remember to take these other medicines as directed by your doctor to achieve the best 
results for your health.

How to take Onglyza
The tablets must not be split or cut. Swallow the tablet whole with some water. You can take the tablet 
with or without food. The tablet can be taken at any time of the day, however, try to take your tablet at 
the same time each day. This will help you to remember to take it.

If you take more Onglyza than you should
If you take more tablets than you should, talk to a doctor straight away.

If you forget to take Onglyza
 If you forget to take a dose of Onglyza, take it as soon as you remember it. However, if it is 

nearly time for the next dose, skip the missed dose. 
 Do not take a double dose to make up for a forgotten dose. Never take two doses on the same 

day.

If you stop taking Onglyza
Keep taking Onglyza until your doctor tells you to stop. This is to help keep your blood sugar under 
control.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Some symptoms need immediate medical attention:
You should stop taking Onglyza and see your doctor immediately if you experience the following 
symptoms of low blood sugar: trembling, sweating, anxiety, blurred vision, tingling lips, paleness, 
mood change, vagueness or confusion (hypoglycaemia); seen very commonly (may affect more than 1 
in 10 people).

Symptoms of a serious allergic reaction (seen rarely, may affect up to 1 in 1,000 people) may include:
o Rash
o Raised red patches on your skin (hives)
o Swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or 

swallowing.



43

If you have these symptoms, stop taking Onglyza and call your doctor or nurse right away. Your 
doctor may prescribe a medicine to treat your allergic reaction and a different medicine for your 
diabetes.

You should stop taking Onglyza 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).

You should call your doctor if you experience the following side effect:
 Severe joint pain.

Some patients have had the following side effects while taking Onglyza and metformin:
 Common, (may affect 1 to 10 users in 100): infection of the upper chest or lungs, infection of 

the urinary tract, inflamed stomach or gut usually caused by an infection (gastroenteritis), 
infection of the sinuses with a feeling of pain and fullness behind your cheeks and eyes 
(sinusitis), inflamed nose or throat (nasopharyngitis) (signs of this may include a cold or a sore 
throat), headache, muscle pain (myalgia), vomiting, inflammation of the stomach (gastritis), 
stomach ache and indigestion (dyspepsia).

 Uncommon (may affect 1 to 10 users in 1,000): joint pain (arthralgia) and difficulties in getting 
or maintaining an erection (erectile dysfunction).

Some patients have had the following side effects while taking Onglyza and a sulphonylurea:
 Very common: low blood sugar (hypoglycaemia)
 Common: infection of the upper chest or lungs, infection of the urinary tract, inflamed stomach 

or gut usually caused by an infection (gastroenteritis), infection of the sinuses with a feeling of 
pain and fullness behind your cheeks and eyes (sinusitis), headache, stomach ache and vomiting.

 Uncommon: tiredness, abnormal lipid (fatty acids) levels (dyslipidaemia, 
hypertriglyceridaemia).

Some patients have had the following side effects while taking Onglyza and a thiazolidinedione:
 Common: infection of the upper chest or lungs, infection of the urinary tract, inflamed stomach 

or gut usually caused by an infection (gastroenteritis), infection of the sinuses with a feeling of 
pain and fullness behind your cheeks and eyes (sinusitis), headache, vomiting, stomach ache and 
swelling of the hands, ankles or feet (peripheral oedema).

Some patients have had the following side effects while taking Onglyza and metformin and a 
sulphonylurea:
 Common: dizziness, tiredness, stomach ache and flatulence.

Some patients have had the following additional side effects while taking Onglyza alone: 
 Common: dizziness, diarrhoea and stomach ache.

Some patients have had the following side effects while taking Onglyza alone or in combination:
 Not known (frequency cannot be estimated from the available data): constipation, blistering of 

the skin (bullous pemphigoid)

Some patients have had a small reduction in the number of one type of white blood cells 
(lymphocytes) shown in a blood test when Onglyza was used alone or in combination.

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 



44

system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Onglyza

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 blister and the carton after EXP. 
The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not use this medicine if the package is damaged or shows signs of tampering.

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 to protect the environment.

6. Contents of the pack and other information

What Onglyza contains
- The active substance is saxagliptin. Each film-coated tablet contains 5 mg saxagliptin (as 

hydrochloride).

- The other ingredients are:
 Tablet core: lactose monohydrate; cellulose, microcrystalline (E460i); croscarmellose 

sodium (E468); magnesium stearate.
 Film-coating: polyvinyl alcohol; macrogol 3350; titanium dioxide (E171); talc (E553b) and 

iron oxide red (E172).
 Printing ink: shellac; indigo carmine aluminium lake (E132).

What Onglyza looks like and contents of the pack

 5 mg film-coated tablets are pink, biconvex, round. They have “5” printed on one side and 
“4215” printed on the other side, in blue ink.

 Tablets available in aluminium foil blisters. 
 5 mg tablets are available in pack sizes of 14, 28, 56, or 98 film-coated tablets in non-perforated 

blisters, 14, 28, 56, or 98 film-coated tablets in non-perforated calendar blisters and 30x1 or 
90x1 film-coated tablets in perforated unit dose blisters.

Not all pack sizes may be marketed in your country.

Marketing Authorisation Holder 

AstraZeneca AB
SE-151 85 Södertälje
Sweden

Manufacturer:

AstraZeneca GmbH
Tinsdaler Weg 183
22880 Wedel
Germany

AstraZeneca UK Limited

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


45

Silk Road Business Park
Macclesfield
Cheshire
SK10 2NA
United Kingdom

Bristol-Myers Squibb Company
Contrada Fontana del Ceraso 
IT-03012 Anagni (FR)
Italy

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

België/Belgique/Belgien
AstraZeneca S.A./N.V.
Tel: +32 2 370 48 11

Lietuva
UAB AstraZeneca Lietuva
Tel: +370 5 2660550

България
АстраЗенека България ЕООД
Тел.: +359 (2) 44 55 000

Luxembourg/Luxemburg
AstraZeneca S.A./N.V.
Tél/Tel: +32 2 370 48 11

Česká republika
AstraZeneca Czech Republic s.r.o.
Tel: +420 222 807 111

Magyarország
AstraZeneca Kft.
Tel.: +36 1 883 6500

Danmark
AstraZeneca A/S
Tlf: +45 43 66 64 62

Malta
Associated Drug Co. Ltd
Tel: +356 2277 8000

Deutschland
AstraZeneca GmbH
Tel: +49 41 03 7080

Nederland
AstraZeneca BV
Tel: +31 79 363 2222

Eesti
AstraZeneca 
Tel: +372 6549 600

Norge
AstraZeneca AS
Tlf: +47 21 00 64 00

Ελλάδα
AstraZeneca A.E.
Τηλ: +30 2 106871500

Österreich
AstraZeneca Österreich GmbH
Tel: +43 1 711 31 0

España
AstraZeneca Farmacéutica Spain, S.A.
Tel: +34 91 301 91 00

Polska
AstraZeneca Pharma Poland Sp. z o.o.
Tel.: +48 22 245 73 00

France
AstraZeneca
Tél: +33 1 41 29 40 00

Portugal
AstraZeneca Produtos Farmacêuticos, Lda.
Tel: +351 21 434 61 00

Hrvatska 
AstraZeneca d.o.o.
Tel: +385 1 4628 000

România
AstraZeneca Pharma SRL
Tel: +40 21 317 60 41



46

Ireland
AstraZeneca Pharmaceuticals (Ireland) DAC
Tel: +353 1609 7100

Slovenija
AstraZeneca UK Limited
Tel: +386 1 51 35 600

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
AstraZeneca AB, o.z.
Tel: +421 2 5737 7777

Italia
AstraZeneca S.p.A.
Tel: +39 02 9801 1

Suomi/Finland
AstraZeneca Oy
Puh/Tel: +358 10 23 010

Κύπρος
Αλέκτωρ Φαρµακευτική Λτδ
Τηλ: +357 22490305

Sverige
AstraZeneca AB
Tel: +46 8 553 26 000

Latvija
SIA AstraZeneca Latvija
Tel: +371 67377100

United Kingdom
AstraZeneca UK Ltd
Tel: +44 1582 836 836

This leaflet was last revised in 

Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu. 

http://www.emea.europa.eu/
http://www.emea.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) 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