Medication leaflets

Leaflet ONDIBTA 100U / ml solution for injection in pre-filled pen

Product code:
W72086001
Quantity:
1
Indicated for:
diabetes mellitus
Route of administration:
injectable
Substance:
insulin glargine (insulin)
ATC
A10AE04 — Alimentary tract and metabolism | Insulins and analogues | Insulins and analogues for injection, long-acting
Insulin glargine is a long-acting basal insulin used to control blood sugar levels in people with type 1 and type 2 diabetes. It is an insulin analog, meaning its structure has been modified to provide a slow and steady release of insulin throughout the day, mimicking the natural basal insulin secretion of the pancreas.

Insulin glargine begins to work approximately 1-2 hours after injection and provides a consistent effect for up to 24 hours or longer, without a pronounced peak of action. It is typically administered once daily, at the same time each day, to ensure stable long-term blood sugar control. It is often used in combination with rapid-acting insulins or other antidiabetic medications to manage postprandial (after-meal) blood sugar levels.

While insulin glargine is effective, its use requires caution. Hypoglycemia (excessively low blood sugar) is the most common side effect, especially if the dose is too high or meals are skipped. Other side effects may include injection site reactions, such as redness, swelling, or itching. It is important for patients to regularly monitor their blood sugar levels and follow the dose prescribed by their doctor.

Insulin glargine should be administered as directed by a doctor, and patients should use proper injection techniques. If severe side effects or difficulties in blood sugar control occur, immediate medical attention is necessary. Patients should also be aware of the signs of hypoglycemia and have a source of fast-acting sugar readily available.

General data about ONDIBTA 100U / ml

Substance:
insulin glargine
Date of latest medicines list:
01-08-2026
Product code:
W72086001
Concentration:
100U / ml
Pharmaceutical form:
solution for injection in pre-filled pen
Quantity:
1
Product type:
Generic medicine
Prescription status:
P-RF — Medicines dispensed with a medical prescription that is retained by the pharmacy and cannot be renewed.

Marketing authorisation

Manufacturer:
SANDOZ GMBH - AUSTRIA
Holder:
GAN & LEE PHARMACEUTICALS EUROPE GMBH - GERMANIA
Number:
2000/2026/01
Shelf life:
3 years

Pharmaceutical forms available for insulin glargine

Concentrations available for insulin glargine

  • 100U/ml
  • 100UI/ml
  • 300U/ml

Other substances similar to insulin glargine

Combinations with other substances

Official documents

EMA leaflet
Added to database:
09/04/2026
Source record updated:
21/08/2026

Precautions:

Hypoglycemia

This medicine may lower blood sugar.

Electrolyte disturbances

This medicine may change blood electrolyte levels.

Contents of the package leaflet for the medicine ONDIBTA 100U / ml solution for injection in pre-filled pen

Leaflet ONDIBTA 100U/ml

1. NAME OF THE MEDICINAL PRODUCT

Ondibta 100 units/ml solution for injection in pre-filled pen

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains 100 units insulin glargine* (equivalent to 3.64 mg).

Each pre-filled pen contains 3 ml of solution for injection, equivalent to 300 units.

*Insulin glargine is produced by recombinant DNA technology in Escherichia coli.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection in pre-filled pen (VitaClick)

Clear colourless solution.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Treatment of diabetes mellitus in adults, adolescents and children aged 2 years and above.

4.2 Posology and method of administration

Posology

Ondibta contains insulin glargine, an insulin analogue, and has a prolonged duration of action.

Ondibta should be administered once daily at any time but at the same time each day.

The dose regimen (dose and timing) should be individually adjusted. In patients with type 2 diabetesmellitus, Ondibta can also be given together with orally active antidiabetic medicinal products.

The potency of this medicinal product is stated in units. These units are exclusive to Ondibta and arenot the same as IU or the units used to express the potency of other insulin analogues (see section5.1).

Special populations

Elderly population (≥ 65 years old)

In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulinrequirements.

Renal impairment

In patients with renal impairment, insulin requirements may be diminished due to reduced insulinmetabolism.

Hepatic impairment

In patients with hepatic impairment, insulin requirements may be diminished due to reduced capacityfor gluconeogenesis and reduced insulin metabolism.

Paediatric population

* Adolescents and children aged 2 years and older patients

The safety and efficacy of Ondibta in adolescents and children aged 2 years and older have beenestablished (see section 5.1). The dose regimen (dose and timing) should be individually adjusted.

* Children below 2 years of age

The safety and efficacy of Ondibta have not been established. No data are available.

Switch from other insulins to Ondibta

When switching from a treatment regimen with an intermediate or long-acting insulin to a regimenwith Ondibta, a change of the dose of the basal insulin may be required and the concomitantantidiabetic treatment may need to be adjusted (dose and timing of additional regular insulins orfast-acting insulin analogues or the dose of oral antidiabetic medicinal products).

Switch from twice daily NPH insulin to Ondibta

To reduce the risk of nocturnal and early morning hypoglycaemia, patients who are changing theirbasal insulin regimen from a twice daily NPH insulin to a once daily regimen with Ondibta shouldreduce their daily dose of basal insulin by 20-30% during the first weeks of treatment.

Switch from insulin glargine 300 units/ml to Ondibta

Ondibta and insulin glargine 300 units/ml are not bioequivalent and are not directly interchangeable.

To reduce the risk of hypoglycaemia, patients who are changing their basal insulin regimen from aninsulin regimen with once daily insulin glargine 300 units/ml to a once daily regimen with Ondibtashould reduce their dose by approximately 20%.

During the first weeks the reduction should, at least partially, be compensated by an increase inmealtime insulin, after this period the regimen should be adjusted individually.

Close metabolic monitoring is recommended during the switch and in the initial weeks thereafter.

With improved metabolic control and resulting increase in insulin sensitivity a further adjustment indose regimen may become necessary. Dose adjustment may also be required, for example, if thepatient's weight or life-style changes, change of timing of insulin dose or other circumstances arisethat increase susceptibility to hypo- or hyperglycaemia (see section 4.4).

Patients with high insulin doses because of antibodies to human insulin may experience an improvedinsulin response with Ondibta.

Method of administration

Ondibta is administered subcutaneously.

Ondibta should not be administered intravenously. The prolonged duration of action of Ondibta isdependent on its injection into subcutaneous tissue. Intravenous administration of the usualsubcutaneous dose could result in severe hypoglycaemia.

There are no clinically relevant differences in serum insulin or glucose levels after abdominal,deltoid or thigh administration of Ondibta. Injection sites must be rotated within a given injectionarea from one injection to the next in order to reduce the risk of lipodystrophy and cutaneousamyloidosis (see section 4.4 and 4.8).

Ondibta must not be mixed with any other insulin or diluted. Mixing or diluting can change itstime/action profile and mixing can cause precipitation.

Before using Ondibta, the instructions for use included in the package leaflet must be read carefully(see section 6.6).

4.3 Contraindications

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

4.4 Special warnings and precautions for use

Traceability

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

Ondibta is not the insulin of choice for the treatment of diabetic ketoacidosis. Instead, regular insulinadministered intravenously is recommended in such cases.

In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, thepatient's adherence to the prescribed treatment regimen, injection sites and proper injectiontechnique and all other relevant factors must be reviewed before dose adjustment is considered.

Transferring a patient to another type or brand of insulin should be done under strict medicalsupervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long-acting, etc.),origin (animal, human, human insulin analogue) and/or method of manufacture may result in theneed for a change in dose.

Patients must be instructed to perform continuous rotation of the injection site to reduce the risk ofdeveloping lipodystrophy and cutaneous amyloidosis. There is a potential risk of delayed insulinabsorption and worsened glycaemic control following insulin injections at sites with these reactions.

A sudden change in the injection site to an unaffected area has been reported to result inhypoglycaemia. Blood glucose monitoring is recommended after the change in the injection site,and dose adjustment of antidiabetic medications may be considered.

Hypoglycaemia

The time of occurrence of hypoglycaemia depends on the action profile of the insulins used andmay, therefore, change when the treatment regimen is changed. Due to more sustained basal insulinsupply with Ondibta, less nocturnal but more early morning hypoglycaemia can be expected.

Particular caution should be exercised, and intensified blood glucose monitoring is advisable inpatients in whom hypoglycaemic episodes might be of particular clinical relevance, such as inpatients with significant stenoses of the coronary arteries or of the blood vessels supplying the brain(risk of cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferativeretinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis followinghypoglycaemia).

Patients should be aware of circumstances where warning symptoms of hypoglycaemia arediminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or beabsent in certain risk groups. These include patients:

- in whom glycaemic control is markedly improved,

- in whom hypoglycaemia develops gradually,

- who are elderly,

- after transfer from animal insulin to human insulin,

- in whom an autonomic neuropathy is present,

- with a long history of diabetes,

- suffering from a psychiatric illness,

- receiving concurrent treatment with certain other medicinal products (see section 4.5).

Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to thepatient's awareness of hypoglycaemia.

The prolonged effect of subcutaneous insulin glargine may delay recovery from hypoglycaemia.

If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent,unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered.

Adherence of the patient to the dose and dietary regimen, correct insulin administration andawareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factorsincreasing the susceptibility to hypoglycaemia require particularly close monitoring and maynecessitate dose adjustment. These include:

- change in the injection area,

- improved insulin sensitivity (e.g., by removal of stress factors),

- unaccustomed, increased or prolonged physical activity,

- intercurrent illness (e.g. vomiting, diarrhoea),

- inadequate food intake,

- missed meals,

- alcohol consumption,

- certain uncompensated endocrine disorders, (e.g. in hypothyroidism and inanterior pituitary or adrenocortical insufficiency),

- concomitant treatment with certain other medicinal products (see section 4.5).

Intercurrent illness

Intercurrent illness requires intensified metabolic monitoring. In many cases urine tests for ketonesare indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is oftenincreased. Patients with type 1 diabetes must continue to consume at least a small amount ofcarbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomitingetc. and they must never omit insulin entirely.

Insulin antibodies

Insulin administration may cause insulin antibodies to form. In rare cases, the presence of suchinsulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency tohyper- or hypoglycaemia (see section 5.1).

Handling of Ondibta pre-filled pen

Ondibta 100 units/ml in pre-filled pen is only suitable for subcutaneous injections. Before using

Ondibta, the instructions for use included in the package leaflet must be read carefully. Ondibta hasto be used as recommended in these instructions for use (see section 6.6).

Medication errors

Medication errors have been reported in which other insulins, particularly short-acting insulins, havebeen accidentally administered instead of insulin glargine. Insulin label must always be checkedbefore each injection to avoid medication errors between insulin glargine and other insulins.

Combination of Ondibta with pioglitazone

Cases of cardiac failure have been reported when pioglitazone was used in combination withinsulin, especially in patients with risk factors for development of cardiac heart failure. This shouldbe kept in mind if treatment with the combination of pioglitazone and Ondibta is considered. If thecombination is used, patients should be observed for signs and symptoms of heart failure, weightgain and oedema.

Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs.

Excipients with known effect

This medicinal product contains less than 1 mmol (23 mg) sodium per dose, thatis to say essentially ‘sodium-free’.

4.5 Interaction with other medicinal products and other forms of interaction

A number of substances affect glucose metabolism and may require dose adjustment of insulinglargine.

Substances that may enhance the blood-glucose-lowering effect and increase susceptibility tohypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE)inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline,propoxyphene, salicylates and sulfonamide antibiotics.

Substances that may reduce the blood-glucose-lowering effect include corticosteroids, danazol,diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens, phenothiazine derivatives,somatropin, sympathomimetic medicinal products (e.g. epinephrine [adrenaline], salbutamol,terbutaline), thyroid hormones, atypical antipsychotic medicinal products (e.g. clozapine andolanzapine) and protease inhibitors.

Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken theblood-glucose-lowering effect of insulin. Pentamidine may cause hypoglycaemia, which maysometimes be followed by hyperglycaemia.

In addition, under the influence of sympatholytic medicinal products such as beta-blockers,clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced orabsent.

4.6 Fertility, pregnancy and lactation

Pregnancy

For insulin glargine no clinical data on exposed pregnancies from controlled clinical studies areavailable. A large amount of data on pregnant women (more than 1 000 pregnancy outcomes)indicate no specific adverse effects of insulin glargine on pregnancy and no specific malformativenor foeto/neonatal toxicity of insulin glargine. Animal data do not indicate reproductive toxicity.

The use of Ondibta may be considered during pregnancy, if clinically needed.

It is essential for patients with pre-existing or gestational diabetes to maintain good metaboliccontrol throughout pregnancy to prevent adverse outcomes associated with hyperglycaemia. Insulinrequirements may decrease during the first trimester and generally increase during the second andthird trimesters. Immediately after delivery, insulin requirements decline rapidly (increased risk ofhypoglycaemia). Careful monitoring of glucose control is essential.

Breast-feeding

It is unknown whether insulin glargine is excreted in human milk. No metabolic effects of ingestedinsulin glargine on the breast-fed newborn/infant are anticipated since insulin glargine as a peptide isdigested into aminoacids in the human gastrointestinal tract. Breast-feeding women may requireadjustments in insulin dose and diet.

Fertility

Animal studies do not indicate direct harmful effects with respect to fertility.

4.7 Effects on ability to drive and use machines

The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia orhyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk insituations where these abilities are of special importance (e.g. driving a car or using machines).

Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This isparticularly important in those who have reduced or absent awareness of the warning symptoms ofhypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it isadvisable to drive or use machines in these circumstances.

4.8 Undesirable effects

Summary of the safety profile

Hypoglycaemia (very common), in general the most frequent adverse reaction of insulin therapy,may occur if the insulin dose is too high in relation to the insulin requirement (see section 4.4).

Tabulated list of adverse reactions

The following related adverse reactions from clinical investigations are listed below by systemorgan class and in order of decreasing incidence (very common: ≥ 1/10; common: ≥ 1/100 to < 1/10;uncommon: ≥ 1/1 000 to < 1/100; rare: ≥ 1/10 000 to < 1/1 000; very rare: < 1/10 000; not known:cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

MedDRA Very common Common Uncommon Rare Very rare Not knownsystem organclasses

Immune system Allergicdisorders reactions

Metabolism and Hypoglycaemianutritiondisorders

Nervous system Dysgeusiadisorders

Eye disorders Visualimpairment

Retinopathy

Skin and Lipohypertrophy Lipoatrophy Cutaneoussubcutaneous amyloidosistissue disorders

Musculoskeletal Myalgiaand connectivetissue disorders

General disorders Injection site Oedemaand administration reactionssite conditions

Description of selected adverse reactions
Metabolism and nutrition disorders

Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. Prolongedor severe hypoglycaemic episodes may be life-threatening.

In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergiccounter-regulation. Generally, the greater and more rapid the decline in blood glucose, the moremarked is the phenomenon of counter-regulation and its symptoms (see section 4.4).

Immune system disorders

Immediate-type allergic reactions to insulin are rare. Such reactions to insulin (including insulinglargine) or the excipients may, for example, be associated with generalised skin reactions,angio-oedema, bronchospasm, hypotension and shock, and may be life-threatening.

Eye disorders

A marked change in glycaemic control may cause temporary visual impairment, due to temporaryalteration in the turgidity and refractive index of the lens.

Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy.

However, intensification of insulin therapy with abrupt improvement in glycaemic control may beassociated with temporary worsening of diabetic retinopathy. In patients with proliferativeretinopathy, particularly if not treated with photocoagulation, severe hypoglycaemic episodes mayresult in transient amaurosis.

Skin and subcutaneous tissue disorders

Lipodystrophy and cutaneous amyloidosis may occur at the injection site and delay local insulinabsorption. Continuous rotation of the injection site within the given injection area may help toreduce or prevent these reactions (see section 4.4).

General disorders and administration site conditions

Injection site reactions include redness, pain, itching, hives, swelling, or inflammation. Most minorreactions to insulins at the injection site usually resolve in a few days to a few weeks.

Rarely, insulin may cause sodium retention and oedema particularly if previously poor metaboliccontrol is improved by intensified insulin therapy.

Paediatric population

In general, the safety profile for children and adolescents (≤ 18 years of age) is similar to the safetyprofile for adults.

The adverse reaction reports received from post marketing surveillance included relatively morefrequent injection site reactions (injection site pain, injection site reaction) and skin reactions (rash,urticaria) in children and adolescents (≤ 18 years of age) than in adults.

Clinical study safety data are not available for children under 2 years.

Reporting of suspected adverse reactions

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.

4.9 Overdose

Symptoms

Insulin overdose may lead to severe and sometimes long-term and life-threatening hypoglycaemia.

Management

Mild episodes of hypoglycaemia can usually be treated with oral carbohydrates. Adjustments in doseof the medicinal product, meal patterns, or physical activity may be needed.

More severe episodes with coma, seizure, or neurologic impairment may be treated with glucagon orconcentrated intravenous glucose. Sustained carbohydrate intake and observation may be necessarybecause hypoglycaemia may recur after apparent clinical recovery.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs used in diabetes, insulins and analogues for injection,long-acting. ATC Code: A10AE04.

Ondibta is a biosimilar medicinal product. Detailed information is available on the website of the

European Medicines Agency https://ema.europa.eu.

Mechanism of action

Insulin glargine is a human insulin analogue designed to have a low solubility at neutral pH. It iscompletely soluble at the acidic pH of the Ondibta injection solution (pH 4). After injection into thesubcutaneous tissue, the acidic solution is neutralised leading to formation of micro-precipitates fromwhich small amounts of insulin glargine are continuously released, providing a smooth, peakless,predictable concentration/time profile with a prolonged duration of action.

Insulin glargine is metabolised into 2 active metabolites M1 and M2 (see section 5.2).

Insulin receptor binding: In vitro studies indicate that the affinity of insulin glargine and itsmetabolites M1 and M2 for the human insulin receptor is similar to the one of human insulin.

IGF-1 receptor binding: The affinity of insulin glargine for the human IGF-1 receptor isapproximately 5 to 8-fold greater than that of human insulin (but approximately 70 to 80-fold lowerthan the one of IGF-1), whereas M1 and M2 bind the IGF-1 receptor with slightly lower affinitycompared to human insulin.

The total therapeutic insulin concentration (insulin glargine and its metabolites) found in type 1diabetic patients was markedly lower than what would be required for a half maximal occupation ofthe IGF-1 receptor and the subsequent activation of the mitogenic-proliferative pathway initiated bythe IGF-1 receptor. Physiological concentrations of endogenous IGF-1 may activate the mitogenic-proliferative pathway; however, the therapeutic concentrations found in insulin therapy, including in

Ondibta therapy, are considerably lower than the pharmacological concentrations required toactivate the IGF-1 pathway.

The primary activity of insulin, including insulin glargine, is regulation of glucose metabolism.

Insulin and its analogues lower blood glucose levels by stimulating peripheral glucose uptake,especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibitslipolysis in the adipocyte, inhibits proteolysis and enhances protein synthesis.

In clinical pharmacology studies, intravenous insulin glargine and human insulin have been shownto be equipotent when given at the same doses. As with all insulins, the time course of action ofinsulin glargine may be affected by physical activity and other variables.

In euglycaemic clamp studies in healthy subjects or in patients with type 1 diabetes, the onset ofaction of subcutaneous insulin glargine was slower than with human NPH insulin, its effect profilewas smooth and peakless, and the duration of its effect was prolonged.

The following graph shows the results from a study in patients:

Activity profile in patients with type 1 diabetes

*determined as amount of glucose infused to maintain constant plasma glucose levels (hourly meanvalues)

The longer duration of action of subcutaneous insulin glargine is directly related to its slower rate ofabsorption and supports once daily administration. The time course of action of insulin and insulinanalogues such as insulin glargine may vary considerably in different individuals or within the sameindividual.

In a clinical study, symptoms of hypoglycaemia or counter-regulatory hormone responses weresimilar after intravenous insulin glargine and human insulin both in healthy volunteers and patientswith type 1 diabetes.

In clinical studies, antibodies that cross-react with human insulin and insulin glargine were observedwith the same frequency in both NPH-insulin and insulin glargine treatment groups.

Effects of insulin glargine (once daily) on diabetic retinopathy were evaluated in an open-label5 year NPH-controlled study (NPH given bid) in 1 024 type 2 diabetic patients in which progressionof retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study (ETDRS)scale was investigated by fundus photography. No significant difference was seen in the progressionof diabetic retinopathy when insulin glargine was compared to NPH insulin.

The ORIGIN (Outcome Reduction with Initial Glargine INtervention) study was a multicenter,randomised, 2x2 factorial design study conducted in 12 537 participants at high cardiovascular (CV)risk with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) (12% of participants)or type 2 diabetes mellitus treated with ≤ 1 antidiabetic oral agent (88% of participants). Participantswere randomised (1:1) to receive insulin glargine (n=6 264), titrated to reach FPG ≤ 95 mg/dl(5.3 mM), or standard care (n=6 273).

The first co-primary efficacy outcome was the time to the first occurrence of CV death, nonfatalmyocardial infarction (MI), or nonfatal stroke, and the second co-primary efficacy outcome was thetime to the first occurrence of any of the first co-primary events, or revascularisation procedure(coronary, carotid, or peripheral), or hospitalisation for heart failure.

Secondary endpoints included all-cause mortality and a composite microvascular outcome.

Insulin glargine did not alter the relative risk for CV disease and CV mortality when compared tostandard of care. There were no differences between insulin glargine and standard care for the twoco-primary outcomes; for any component endpoint comprising these outcomes; for all-causemortality; or for the composite microvascular outcome.

Mean dose of insulin glargine by study end was 0.42 U/kg. At baseline, participants had a median

HbA1c value of 6.4% and median on-treatment HbA1c values ranged from 5.9 to 6.4% in theinsulin glargine group, and 6.2% to 6.6% in the standard care group throughout the duration offollow-up.

The rates of severe hypoglycaemia (affected participants per 100 participant years of exposure) were1.05 for insulin glargine and 0.30 for standard care group and the rates of confirmed non-severehypoglycaemia were 7.71 for insulin glargine and 2.44 for standard care group. Over the course ofthis 6-year study, 42% of the insulin glargine group did not experience any hypoglycaemia.

At the last on-treatment visit, there was a mean increase in body weight from baseline of 1.4 kg inthe insulin glargine group and a mean decrease of 0.8 kg in the standard care group.

Paediatric population

In a randomised, controlled clinical study, paediatric patients (age range 6 to 15 years) with type 1diabetes (n=349) were treated for 28 weeks with a basal-bolus insulin regimen where regular humaninsulin was used before each meal. Insulin glargine was administered once daily at bedtime and

NPH human insulin was administered once or twice daily. Similar effects on glycohemoglobin andthe incidence of symptomatic hypoglycaemia were observed in both treatment groups, howeverfasting plasma glucose decreased more from baseline in the insulin glargine group than in the NPHgroup.

There was less severe hypoglycaemia in the insulin glargine group as well. One hundred forty threeof the patients treated with insulin glargine in this study continued treatment with insulin glargine inan uncontrolled extension study with mean duration of follow-up of 2 years. No new safety signalswere seen during this extended treatment with insulin glargine.

A crossover study comparing insulin glargine plus lispro insulin to NPH plus regular human insulin(each treatment administered for 16 weeks in random order) in 26 adolescent type 1 diabetic patientsaged 12 to 18 years was also performed. As in the paediatric study described above, fasting plasmaglucose reduction from baseline was greater in the insulin glargine group than in the NPH group.

HbA1c changes from baseline were similar between treatment groups; however blood glucose valuesrecorded overnight were significantly higher in the insulin glargine/ lispro group than the

NPH/regular group, with a mean nadir of 5.4 mM versus 4.1 mM. Correspondingly, the incidencesof nocturnal hypoglycaemia were 32% in the insulin glargine/lispro group versus 52% in the

NPH/regular group.

A 24-week parallel group study was conducted in 125 children with type 1 diabetes mellitus aged 2to 6 years, comparing insulin glargine given once daily in the morning to NPH insulin given once ortwice daily as basal insulin. Both groups received bolus insulin before meals.

The primary aim of demonstrating non-inferiority of insulin glargine to NPH in all hypoglycaemiawas not met and there was a trend to an increase of hypoglycaemic events with insulin glargine[insulin glargine: NPH rate ratio (95% CI) = 1.18 (0.97-1.44)].

Glycohaemoglobin and glucose variabilities were comparable in both treatment groups.

No new safety signals were observed in this study.

5.2 Pharmacokinetic properties

In healthy subjects and diabetic patients, insulin serum concentrations indicated a slower and muchmore prolonged absorption and showed a lack of a peak after subcutaneous injection of insulinglargine in comparison to human NPH insulin. Concentrations were thus consistent with the timeprofile of the pharmacodynamic activity of insulin glargine. The graph above shows the activityprofiles over time of insulin glargine and NPH insulin.

Insulin glargine injected once daily will reach steady state levels in 2-4 days after the first dose.

When given intravenously the elimination half-life of insulin glargine and human insulin werecomparable.

After subcutaneous injection of Ondibta in diabetic patients, insulin glargine is rapidly metabolizedat the carboxyl terminus of the Beta chain with formation of two active metabolites M1(21A-Gly-insulin) and M2 (21A-Gly-des-30B-Thr-insulin). In plasma, the principal circulatingcompound is the metabolite M1. The exposure to M1 increases with the administered dose of

Ondibta. The pharmacokinetic and pharmacodynamic findings indicate that the effect of thesubcutaneous injection with Ondibta is principally based on exposure to M1. Insulin glargine andthe metabolite M2 were not detectable in the vast majority of subjects and, when they weredetectable their concentration was independent of the administered dose of Ondibta.

In clinical studies, subgroup analyses based on age and gender did not indicate any difference insafety and efficacy in insulin glargine-treated patients compared to the entire study population.

Paediatric population

Pharmacokinetics in children aged 2 to less than 6 years with type 1 diabetes mellitus was assessedin one clinical study (see section 5.1). Plasma “trough” levels of insulin glargine and its main M1and M2 metabolites were measured in children treated with insulin glargine, revealing plasmaconcentration patterns similar to adults, and providing no evidence for accumulation of insulinglargine or its metabolites with chronic dosing.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safetypharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Zinc chloride

Metacresol

Glycerol

Hydrochloric acid (for pH adjustment)

Sodium hydroxide (for pH adjustment)

Water for injections

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

3 years

Shelf-life after first use of the pen

The medicinal product may be stored for a maximum of 4 weeks not above 30 °C and away fromdirect heat or direct light.

The pre-filled pens in use must not be stored in the refrigerator. The pen cap must be put back onthe pen after each injection in order to protect from light.

6.4 Special precautions for storage

Not in-use Ondibta pre-filled pens

Store in a refrigerator (2 °C-8 °C).

Do not freeze or place next to the freezer compartment or a freezer pack.

Keep Ondibta pre-filled pen in the outer carton in order to protect from light.

In-use Ondibta pre-filled pens

For storage conditions after first opening of this medicinal product, see section 6.3.

6.5 Nature and contents of container

Type 1 colourless glass cartridge with a red plunger (bromobutyl rubber) and a flanged cap(aluminium) with a stopper (bromobutyl rubber and synthetic polyisoprene-EPDM blend)containing 3 ml of solution.

The cartridge is sealed in a disposable pen injector.

Needles are not included in the pack.

Packs of 1, 5 or a multipack of 10 (2 packs of 5) Ondibta pre-filled pens.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Inspect Ondibta before use. It must only be used if the solution is clear, colourless, with no solidparticles visible, and if it is of water-like consistency. Since Ondibta is a solution, it does not requireresuspension before use.

Ondibta must not be mixed with any other insulin or diluted. Mixing or diluting can change itstime/action profile and mixing can cause precipitation.

Insulin label must always be checked before each injection to avoid medication errors betweeninsulin glargine and other insulins (see section 4.4).

Ondibta 100 units/ml in pre-filled pen is only suitable for subcutaneous injections.

Before first use, the pre-filled pen must be stored at room temperature for 1 to 2 hours. Emptypre-filled pens must never be reused and must be properly discarded.

To prevent the possible transmission of disease, each pen must be used by one patient only.

Before using the pre-filled pen, the instructions for use included in the package leaflet must be readcarefully.

7. MARKETING AUTHORISATION HOLDER

Sandoz GmbH

Biochemiestrasse 106250 Kundl

Austria

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/25/2000/001

EU/1/25/2000/002

EU/1/25/2000/003

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 09 January 2026

10. DATE OF REVISION OF THE TEXT

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

Medicines Agency https://www.ema.europa.eu

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