Overview of Insulatard

Quick Facts

Property	Description
Active Ingredient	Isophane Insulin (human) (NPH)
Form	Sterile suspension for injection
Pharmacological Class	Antidiabetic agent (Intermediate-acting)
General Purpose	Provides basal glucose regulation
Origin	Biosynthetic (Recombinant DNA technology)

What Type of Insulin Preparation is Insulatard?

Insulatard is an intermediate-acting insulin preparation classified as an antidiabetic agent, utilized for systemic glucose regulation. Its active ingredient is Isophane Insulin (human), a specific chemical form that provides a prolonged pharmacological effect after administration. This medicine is designed to maintain blood sugar levels over a sustained period through its intermediate duration of action.

This pharmaceutical entity belongs to the class of hypoglycemic agents and is produced using Recombinant DNA technology (rDNA), defining it as a biosynthetic human insulin. Insulatard is a major brand for this formulation, often delivered in specific injection devices like the FlexPen or Penfill, differentiating its administration system.

Composition and Origin: Isophane Insulin and Biosynthetic Form

The structure of Insulatard is characterized by its delivery as a cloudy, white sterile suspension for subcutaneous injection. The Isophane formulation is achieved by chemically complexing the Insulin (human) molecule with protamine and zinc within an aqueous vehicle.

This specific composition is the factor that dictates the drug's sustained release. The insulin is slowly released from the protamine complex after injection, leading to its intermediate action profile. This type of insulin is used as a tool for achieving consistent blood sugar control.

Insulatard’s General Purpose in Blood Sugar Control

The general therapeutic purpose of Insulatard is to establish and maintain a necessary basal level of insulin activity in the body. Its intermediate action profile provides a broad and consistent supply of the hormone over many hours. By delivering this sustained action, the preparation helps achieve stable blood sugar control by managing the constant glucose output from the liver and preventing excessive hyperglycemia, particularly during the overnight fasting state.

What side effects are possible with Insulatard?

Possible Side Effects and Safety Information

The safety profile for Isophane Insulin human (Insulatard) is organized and communicated through specific classifications defined in regulatory documents.

Frequency-Classified Adverse Reactions

The most frequently documented adverse reaction is Hypoglycaemia (low blood glucose), which is classified as Very Common in official labeling. Uncommon reactions may include local injection site reactions (such as redness, pain, or swelling), Oedema (swelling), and changes in fat tissue known as Lipodystrophy. Very Rare events documented by regulatory bodies include Anaphylactic Reactions (severe systemic hypersensitivity) and temporary Refraction Disorders (vision issues).

System-Organ-Class Grouping

Adverse effects are grouped by the body system affected. Metabolism and Nutrition Disorders primarily cover hypoglycemia. Skin and Subcutaneous Tissue Disorders include Lipodystrophy and the less common Cutaneous Amyloidosis. Effects on the Eye Disorders may involve temporary worsening of diabetic retinopathy upon rapid improvement of control, or temporary refraction changes.

Time-Related Safety Patterns

Official prescribing information notes that certain effects, such as oedema and refraction disorders, are often transitory and may be observed at the beginning of insulin treatment. Similarly, rapid improvement in blood glucose control may be associated with a temporary worsening of diabetic retinopathy or acute painful neuropathy.

Safety-Related Restrictions

This medicine is formally contraindicated during an episode of ongoing hypoglycaemia and in individuals with a known hypersensitivity to the formulation. Continuous rotation of the injection site is noted in official documents to help mitigate the risk of Lipodystrophy and Cutaneous Amyloidosis.

Overdose and Emergency Response

Overdose and when to seek help

The official regulatory profile for Insulatard overdose is defined by the predictable metabolic event resulting from excessive insulin action: hypoglycemia (low blood sugar). Overdose itself is not quantified by a specific administered dose but by the resulting severity of hypoglycemia relative to individual requirements. The presentation of overdose can range from initial symptoms to severe central nervous system impairment.

Domain	Official Regulatory Statement
Documented Manifestations	Symptoms range from mild signs of low blood sugar to severe effects such as neurologic impairment, seizures, and unconsciousness, affecting the metabolic and central nervous systems.
Life-Threatening Risks	Severe hypoglycemia may be life-threatening and can potentially cause death. A secondary risk, hypokalemia (low blood potassium), may also occur and is considered a serious complication requiring prompt medical correction.
Urgent Medical Action	Seek immediate medical attention for severe episodes, particularly if the individual becomes unconscious or experiences seizures. Mild hypoglycemia requires immediate treatment with oral glucose; severe episodes mandate intervention with glucagon or intravenous glucose.

Monitoring and Special Considerations

Due to Insulatard's intermediate action profile, a critical requirement after initial treatment is sustained observation and carbohydrate intake to manage the potential for recurrent hypoglycemia. Patients with underlying renal or hepatic impairment are officially noted to have an increased risk for severe hypoglycemia in this context.

Therapeutic Uses of Insulatard

What Insulatard Treats: Main Uses and Benefits

Insulatard's primary therapeutic domain involves managing diabetes mellitus by addressing chronic hyperglycemia—the persistently high blood sugar levels characteristic of both Type 1 and Type 2 diabetes. Its use supports the establishment of the necessary, ongoing basal insulin supply, which assists with consistent systemic regulation and overall metabolic control. This intermediate-acting preparation provides sustained action, and may assist in managing high blood sugar during extended periods without food.

The core indications for this medication include conditions requiring insulin replacement therapy in adults, children, and adolescents. Its intermediate duration of action makes it relevant for basal insulin deficiency, helping to manage high blood sugar during extended periods without food.

“The sustained action provided by intermediate-acting insulin contributes to easing the overall symptom load related to high blood sugar between meals and during the overnight fasting state.”

By helping patients achieve and maintain stable blood sugar control, this therapy may assist with mitigating future health risks. Consistent glycemic regulation is commonly used to help with reducing the risk of serious long-term complications of diabetes, including damage to the kidneys, eyes, and nerves.

Quick Fact: Relief for Basal Deficiency
Insulatard is used to provide the foundational basal component for individuals needing comprehensive treatment, and may support sustained regulation of systemic glucose levels across the 24-hour cycle.

Regulatory References

European Medicines Agency (EMA) public assessment of Insulatard

Eligibility and Restrictions for Use

Eligibility Scope

Populations for whom use is allowed (as stated in label):

Adults
Children and Adolescents
Pregnant Individuals (with recommended intensified monitoring)

Populations for whom use is contraindicated:

Individuals experiencing, or suspected of experiencing, Hypoglycemia (low blood sugar) [Source 1.6].
Individuals with documented Hypersensitivity (allergy) to human insulin or any excipients [Source 1.6].

Age and Condition-Specific Eligibility Rules

Age-related eligibility rules:

Adults, Children, and Adolescents are approved populations [Source 1.9].
Older Adults are approved but require intensified glucose monitoring [Source 1.9].

Condition-specific eligibility rules:

Use in patients with Renal Impairment or Hepatic Impairment requires conditional monitoring (intensified blood glucose control) [Source 1.5, 1.6].
Pregnancy and Lactation are permitted states for treatment, though intensified monitoring is recommended during pregnancy [Source 1.7].
Conditional use is required for patients with risk factors for Congestive Heart Failure when co-treated with thiazolidinediones [Source 1.5].

Connection to the Official Eligibility Profile

Regulatory documents define Insulatard eligibility by establishing two absolute prohibitions: the acute state of hypoglycemia and a history of hypersensitivity to the drug. For the broadly permitted populations (including adults and children), eligibility is conditionally constrained by the presence of impaired renal or hepatic function, requiring mandatory intensified monitoring.

What should I know about interactions with other medicines?

Interactions with other medicines and products

The interaction profile of Insulatard (Isophane Insulin human) is defined by pharmacodynamic changes in the patient's insulin requirement, as documented in government regulatory sources. Co-administration with numerous medicinal products may alter the overall glucose-lowering effect, requiring consideration based on the official label.

Agents Modifying Insulin Requirement

Interaction Type	Examples of Interacting Agents
Reduced Insulin Requirement (Increased Glucose-Lowering Effect)	Oral hypoglycaemic agents, MAOI, ACE inhibitors, Salicylates, Anabolic steroids, Sulphonamides.
Increased Insulin Requirement (Reduced Glucose-Lowering Effect)	Oral contraceptives, Thiazides, Glucocorticoids, Thyroid hormones, Beta-sympathomimetics, Growth hormone, Danazol.

Mechanism of Action

Insulatard delivers isophane human insulin, which acts as a non-selective agonist at the ubiquitously expressed Insulin Receptor (IR). The IR is a heterotetrameric transmembrane glycoprotein comprising two extracellular alpha-subunits and two transmembrane beta-subunits possessing intrinsic tyrosine kinase activity.

Binding of insulin to the alpha-subunits induces a conformational change, leading to the autophosphorylation of the beta-subunits. This initiates the intracellular signaling cascade, primarily through the PI3K/Akt pathway and the MAPK pathway, by phosphorylating downstream substrates, including the Insulin Receptor Substrate (IRS) proteins.

Activation of the PI3K/Akt pathway results in the translocation of Glucose Transporter type 4 (GLUT4) vesicles from the intracellular compartment to the plasma membrane in target cells, specifically skeletal muscle and adipocytes. This facilitates the passive diffusion of glucose into the cells, decreasing circulating blood glucose concentration.

Simultaneously, insulin interaction with the hepatic IR inhibits key enzymes in the gluconeogenesis and glycogenolysis pathways, reducing endogenous glucose production by the liver. Furthermore, insulin promotes glycogenesis (storage as glycogen) in the liver and muscle cells and lipogenesis (fat synthesis) in adipocytes. The isophane formulation, which involves complexation with protamine, delays absorption from the subcutaneous injection site, establishing a sustained basal systemic physiological modulation over approximately 24 hours.

Dosage and Administration Information

Administration Method

Insulatard is an insulin suspension intended for subcutaneous injection. This means the medication is delivered into the fatty layer directly under the skin. Common injection sites include the thighs, the abdominal wall, the buttocks, or the deltoid region of the upper arm.

To ensure consistent absorption and prevent localized skin changes, it is standard practice to rotate injection sites within the same anatomical region. The medication must never be administered into a vein or a muscle.

Preparation of the Suspension

Insulatard is a cloudy, white, milky suspension. Before use, the vial, cartridge, or pre-filled pen must be agitated to ensure the insulin is uniformly mixed. When properly resuspended, the liquid should appear uniformly white and cloudy.

Usage with Other Insulins

Insulatard is a prolonged-acting insulin. In some treatment regimens, it may be used in combination with fast-acting insulins. If mixing insulins in the same syringe, the fast-acting insulin is typically drawn into the syringe first to prevent contamination of the fast-acting vial by the prolonged-acting insulin.

Recent Clinical Evidence

Research evidence / Overview of studies for Insulatard

Evidence for use in Type 1 Diabetes Mellitus

The research evidence for Type 1 diabetes relies on Randomized Controlled Trials (RCTs) and Systematic Reviews. These studies research examined how this intermediate-acting insulin compared against other basal insulin types in studying blood sugar levels. The core measurements taken in these trials included metabolic markers such as Glycosylated Haemoglobin ( HbA1c) and Fasting Plasma Glucose (FPG). Studies also monitored how the total daily insulin dose changed and tracked patterns related to hypoglycaemia, or low blood sugar.

The findings describe patterns observed in the studies regarding overall Glycosylated Haemoglobin ( HbA1c) levels when Isophane Insulin was studied as the basal component of therapy. The evidence so far contributes to understanding symptom patterns by describing how these key metabolic outcomes evolved in the observed populations during the study period. However, the number of participants involved in the initial regulatory trials was modest. Because of this, the sample sizes were modest, and the evidence quality varies across studies when comparing certain outcomes.

Evidence for use in Type 2 Diabetes Mellitus

The majority of research was evaluated in adults with Type 2 diabetes. The evidence base for this condition involves Randomized Controlled Trials (RCTs) and Meta-analyses that pool data from trials. These studies explored the comparison of Isophane Insulin with other basal insulin formulations. The outcomes related to systemic or functional imbalance that were studied included blood sugar markers like HbA1c and FPG, as well as tracking changes in Body Weight.

These studies report how symptoms evolved in the observed populations, and the findings indicate that patterns of Glycosylated Haemoglobin ( HbA1c) levels were observed in trials comparing Isophane Insulin to newer long-acting options. Research highlights changes measured during the study period related to overall glucose levels.

Long-Term Evidence and Maintenance of Observed Responses

Clinical trials for basal insulins are often focused on evaluating outcomes over defined, shorter time intervals, typically ranging from a few months up to one year. Therefore, the available follow-up durations were limited. Most studies observing responses over defined time intervals were not powered or designed to examine the long-term effects of treatment, such as the maintenance of the observed responses or how blood sugar levels are maintained over many years.

Because long-term effects are not fully established, the scientific community recognizes that there is limited information for long-term outcomes relevant to the slow progression of diabetes complications. The evidence contributes to the broader evidence landscape, but certainty remains low when considering outcomes that typically take a decade or more to fully manifest.

Frequently Asked Questions (FAQ)

Common questions about Insulatard (FAQ)

Q: How quickly does Insulatard begin to work after administration?

According to official documentation, the glucose-lowering effect typically begins within 1frac12 hours after Insulatard is administered via subcutaneous injection. This describes its characteristics as an intermediate-acting insulin.

Q: How long can the effect of Insulatard last?

The overall duration of Insulatard's effect can vary based on the dose and the individual patient. Official prescribing information states that the total duration of action generally ranges between 14 and 24 hours.

Q: Why is Insulatard sometimes described as having a 'peak'?

Insulatard is described as having a peak because its effect is not completely steady. Official prescribing information indicates that the maximum glucose-lowering effect is reached between 4 and 8 hours after administration. This period is often referred to as the drug's 'peak' time.

Q: Can physical exercise change the expected duration of Insulatard's effect?

Official patient information notes that increased physical activity or exercise can influence blood glucose levels. If physical activity is increased, it may lead to a lower blood glucose level, which may require dose consideration.

Q: What are the signs of low blood sugar associated with Insulatard?

The most common side effect reported is low blood sugar, or hypoglycaemia. Warning signs for this condition, described in patient materials, may include feeling dizzy, sudden cold sweat, shaking, anxiety, nervousness, rapid heartbeat, and temporary changes in vision.

Q: Is it common to feel tired when starting Insulatard?

While tiredness is not listed as a non-specific adverse reaction, official patient materials list unusual weakness or tiredness as one of the possible warning signs of low blood sugar. Hypoglycaemia is the most frequently documented side effect.

Q: Is Insulatard appropriate for use during pregnancy, according to official information?

Official regulatory documentation states that the treatment of diabetes with insulin, including Insulatard, during pregnancy or breastfeeding is not restricted, as insulin does not pass the placental barrier.

Q: Is Insulatard the same as NPH insulin?

Yes. Insulatard is officially classified as Isophane Human Insulin. This name refers to the formulation that uses protamine to delay absorption, and Isophane Human Insulin is commonly known by its chemical acronym, NPH (Neutral Protamine Hagedorn) insulin.

Q: What is the main reason Insulatard is prescribed?

Insulatard is officially indicated for the treatment of diabetes mellitus (both Type 1 and Type 2). Its main purpose is to help reduce and maintain control over high blood sugar levels in patients with the condition.

Q: What is the difference between Insulatard and fast-acting insulin?

Insulatard is an intermediate-acting insulin designed to provide a steady, long-lasting background (basal) effect for up to 24 hours. Fast-acting insulins, in contrast, are designed for a rapid onset and short duration, usually administered around meal times.

Q: Why do some people need Insulatard and others use different types of insulin?

Official regulatory documents describe Insulatard as a basal insulin component. It is often prescribed as part of a regimen that combines it with a separate fast-acting insulin to manage blood sugar levels consistently throughout the day and night.

Q: Can Insulatard cause changes in weight?

Weight changes are noted in official warnings related to insulin therapy. An observed effect of treatment may include weight gain, which is also highlighted in safety warnings related to using insulin alongside certain other anti-diabetic medications.

Q: Does Insulatard need to be refrigerated?

Yes, unused Insulatard must be stored in a refrigerator, typically maintained at 2 C to 8 C. Once a pen or vial is in use, it can be kept at room temperature (below 30 C) for up to 4 weeks, as described in the SmPC.

Q: Can traveling across time zones affect the use of Insulatard?

Official patient information notes that crossing time zones may require an adjustment to the timing of the injection and changes to the diet plan. The prescribing information notes that these adjustments are generally made with a healthcare provider before travel.

Q: Is Insulatard linked to any long-term effects on the heart or kidneys?

Official research summaries indicate that the clinical trials used for review typically had limited follow-up durations, often up to one year. Therefore, they were not designed or statistically powered to fully examine the long-term effects on complications related to organs like the heart or kidneys.

Q: Why is Insulatard available in different concentration forms (if applicable)?

Insulatard is officially available in a single concentration of 100 IU/ml (International Units per millilitre). It is packaged in different forms, such as vials, cartridges, or pre-filled pens, but the concentration of the medication itself remains the same.

Q: What research evidence supports the use of Insulatard for managing blood sugar?

The evidence supporting its use is based on clinical trials, including Randomized Controlled Trials, that measured specific metabolic markers. These markers, such as Glycosylated Haemoglobin ( HbA1c) and Fasting Plasma Glucose (FPG), are used to describe how blood sugar control evolved in the studied populations.

Q: What should be done if I suspect an allergic reaction to Insulatard?

Official documentation notes that immediate medical attention is necessary if a severe allergic reaction is suspected. This includes situations where signs of allergy spread across the body, or if sudden, severe symptoms occur, such as difficulty breathing, vomiting, or a rapid heartbeat.

Q: Is there a maximum amount of time Insulatard can be used for?

Insulatard is an established treatment for diabetes, which is a chronic condition that requires continuous management. Regulatory documents do not specify a maximum time period for its ongoing use in patients.

Q: Is there any research on Insulatard's use in people with kidney impairment?

Official documentation notes that individuals with kidney or liver impairment may experience a reduction in their insulin requirement. For safety, intensified blood glucose monitoring is generally necessary in these populations, as noted in the prescribing information.

Q: Why is it important to check blood sugar regularly when using Insulatard?

Monitoring blood sugar levels is described in official patient materials as a key part of managing diabetes. This ongoing process helps to reduce the risk of acute and chronic health problems caused by blood sugar levels that are too high or too low.

Q: Does Insulatard contain latex or any common allergens?

The formulation's list of ingredients includes the preservative metacresol. Official regulatory documents note that this component, like other excipients, may potentially cause allergic reactions in some individuals.

How should Insulatard be stored and disposed of?

How to Store and Dispose of Insulatard?

Insulatard must be stored under specific, regulated conditions to maintain stability. The unopened product requires refrigeration and must be kept at a temperature between 2 C and 8 C (36 F and 46 F).

Storage Constraints:

Do not freeze the product at any time; frozen Insulatard must be discarded.
The in-use product (opened vial or pen) should not be refrigerated and must be stored at room temperature, below 25 C or 30 C.
The maximum in-use shelf-life is 6 weeks (42 days), after which any remaining product must be discarded.
The product must be kept in the original outer carton to protect it from light and heat.
Insulatard must be stored out of the sight and reach of children.

Disposal Requirements:

Used needles and syringes (sharps) must be disposed of immediately in an FDA-cleared sharps disposal container. Unused product and waste must be discarded in accordance with local requirements and should not be placed in household trash or wastewater.

Insulatard