Mixtard (Biphasic Isophane Insulin)
Premixed human insulin for the management of diabetes mellitus
Quick Facts About Mixtard
Key Takeaways About Mixtard
- Premixed convenience: Mixtard combines fast-acting and intermediate-acting insulin in one injection, simplifying insulin regimens for many patients with diabetes
- Hypoglycaemia awareness: Low blood sugar is the most common side effect; always carry fast-acting glucose and learn to recognise the warning signs
- Consistent meal timing: Because Mixtard has a fixed ratio, meals should be eaten at regular times to match the insulin's peak action
- Proper resuspension is critical: Always roll or tip the pen/vial gently at least 20 times before each injection until the liquid is uniformly white and cloudy
- Safe during pregnancy: Human insulin does not cross the placenta; good blood glucose control during pregnancy is essential for both mother and baby
What Is Mixtard and What Is It Used For?
Mixtard is a premixed human insulin used to treat diabetes mellitus. It contains 30% soluble insulin (fast-acting) for mealtime glucose control and 70% isophane insulin (intermediate-acting) for basal glucose coverage. It is used in both type 1 and type 2 diabetes when blood sugar cannot be adequately controlled by other means.
Mixtard belongs to a group of medicines called biphasic insulins. It is manufactured by Novo Nordisk using recombinant DNA technology to produce human insulin that is identical to the insulin naturally produced by the pancreas. The name "Mixtard 30" refers to the proportion of soluble insulin in the mixture: 30% fast-acting and 70% intermediate-acting. Other ratios, such as Mixtard 50 (50:50), are also available in some markets.
In people with diabetes, the pancreas either produces no insulin (type 1 diabetes) or produces insufficient insulin or the body cannot use it effectively (type 2 diabetes). Insulin is essential for transporting glucose from the bloodstream into cells, where it is used as energy. Without adequate insulin, blood glucose levels rise dangerously high, a condition known as hyperglycaemia, which over time causes serious damage to blood vessels, nerves, kidneys, eyes, and the heart.
Mixtard is designed to mimic the body's natural insulin response. The soluble insulin component begins working within approximately 30 minutes of injection and reaches its peak effect between 1 and 3 hours. This controls the rise in blood glucose that occurs after eating a meal. The isophane insulin component has a slower onset and lasts much longer, maintaining basal glucose control for up to 24 hours. Together, these two components reduce the number of daily injections needed compared to using fast-acting and long-acting insulins separately.
Mixtard is available in several delivery formats to suit different patient needs. Mixtard 30 Penfill cartridges are designed for use with Novo Nordisk reusable insulin pens. Mixtard 30 FlexPen and Mixtard 30 InnoLet are prefilled disposable pen devices. Vials of Mixtard are also available for use with insulin syringes. All contain 100 IU/mL of insulin (or 40 IU/mL in some markets).
Who should use Mixtard?
Mixtard is prescribed for patients with diabetes mellitus who require insulin therapy. This includes all patients with type 1 diabetes and many patients with type 2 diabetes whose blood glucose is not sufficiently controlled with oral antidiabetic medications, lifestyle changes, or other non-insulin therapies. It is used in adults, adolescents, and children aged 2 years and older.
The premixed formulation is particularly suited to patients who benefit from a simplified insulin regimen. For patients who find it difficult to mix their own insulins or who prefer fewer injections, Mixtard offers an effective solution. However, patients requiring very flexible dose adjustments or those with highly variable eating patterns may benefit more from a basal-bolus regimen using separate insulin preparations.
What Should You Know Before Taking Mixtard?
Do not use Mixtard if you are allergic to human insulin or any of its ingredients, or if you are experiencing hypoglycaemia. Tell your doctor about all medical conditions and medications you are taking, as many drugs affect blood sugar levels. Insulin requirements change during illness, stress, and changes in physical activity.
Before starting treatment with Mixtard, it is essential that your healthcare provider has a complete picture of your medical history and current medications. Several conditions and circumstances require special consideration when using insulin therapy. Understanding these precautions helps ensure safe and effective treatment.
Contraindications
You must not use Mixtard in the following situations:
- Hypersensitivity: If you are allergic to human insulin, metacresol, protamine sulphate, or any of the other excipients in Mixtard
- Hypoglycaemia: Never inject insulin when your blood glucose is already low; treat the hypoglycaemia first
- Insulin pump use: Mixtard must never be used in insulin infusion pumps due to the isophane component, which can clog the pump mechanism
- Intravenous injection: Mixtard suspension must never be administered intravenously; only clear, soluble insulin preparations can be given by this route
Warnings and Precautions
Talk to your doctor, pharmacist, or diabetes nurse before using Mixtard if you have any of the following conditions or circumstances:
- Kidney or liver problems: These conditions may reduce insulin clearance, leading to lower insulin requirements and increased risk of hypoglycaemia
- Adrenal, pituitary, or thyroid disorders: Endocrine conditions can significantly affect glucose metabolism and insulin needs
- Intensive physical exercise: Increases glucose uptake and may cause hypoglycaemia; adjust your dose or food intake accordingly
- Travelling across time zones: Consult your doctor as you may need to adjust your injection and meal schedule
- Lipodystrophy: Rotate your injection site regularly to reduce the risk of lumps or pits under the skin at the injection site, which can affect insulin absorption
- Thiazolidinedione combination: Using Mixtard with thiazolidinediones (pioglitazone) may increase the risk of heart failure; report any shortness of breath, rapid weight gain, or swelling to your doctor
Hypoglycaemia (low blood sugar) is the most frequent adverse effect of insulin therapy. Warning signs include cold sweat, pale skin, nervousness, trembling, anxiety, unusual tiredness, confusion, difficulty concentrating, excessive hunger, temporary vision changes, headache, nausea, and rapid heartbeat. Always carry fast-acting glucose (glucose tablets, sugary drink) and ensure those around you know how to help.
Pregnancy and Breastfeeding
If you are pregnant, planning to become pregnant, or breastfeeding, talk to your doctor before using Mixtard. Human insulin, including Mixtard, does not cross the placenta and is not known to cause harm to the developing baby. In fact, maintaining good blood glucose control during pregnancy is critically important, as uncontrolled diabetes significantly increases the risk of birth defects, preeclampsia, macrosomia (large baby), and neonatal hypoglycaemia.
Insulin requirements typically change during pregnancy. They often decrease during the first trimester and increase during the second and third trimesters. After delivery, insulin requirements usually return rapidly to pre-pregnancy levels. Close monitoring and dose adjustment by your healthcare team is essential throughout pregnancy and the postpartum period.
Mixtard can be used during breastfeeding. Insulin therapy does not pose a risk to the nursing infant. However, you may need to adjust your Mixtard dose and diet while breastfeeding, as lactation increases caloric expenditure and may affect blood glucose levels.
How Does Mixtard Interact with Other Drugs?
Many medications affect how Mixtard works. Some drugs lower blood sugar further (increasing hypoglycaemia risk), while others raise blood sugar (reducing Mixtard's effectiveness). Always tell your doctor about all medicines, supplements, and herbal products you are taking. Alcohol can also intensify and prolong the blood sugar-lowering effect of insulin.
Drug interactions with insulin can be clinically significant and may require dose adjustment. The following table summarises the most important interactions. Always consult your healthcare provider when starting, stopping, or changing the dose of any medication while using Mixtard.
| Interacting Drug/Class | Effect on Blood Glucose | Clinical Significance | Action Required |
|---|---|---|---|
| Oral antidiabetic agents (metformin, sulfonylureas, GLP-1 agonists) | Increased glucose-lowering effect | Major | Insulin dose reduction may be needed; increased hypoglycaemia monitoring |
| Beta-blockers (propranolol, atenolol, metoprolol) | May mask hypoglycaemia symptoms | Major | Increased blood glucose monitoring; beta-blockers can hide warning signs of low blood sugar |
| ACE inhibitors (enalapril, ramipril, lisinopril) | May enhance insulin sensitivity | Moderate | Monitor blood glucose more closely when starting or adjusting ACE inhibitor |
| Corticosteroids (prednisolone, dexamethasone) | Significant increase in blood glucose | Major | Substantial insulin dose increase often required; close monitoring essential |
| Thiazide diuretics (hydrochlorothiazide, bendroflumethiazide) | Raise blood glucose levels | Moderate | Insulin dose adjustment may be needed |
| Oral contraceptives (combined pill) | May raise blood glucose | Moderate | Monitor blood glucose when starting or stopping; dose adjustment may be needed |
| MAO inhibitors | Enhanced insulin effect | Major | Dose reduction may be required; close monitoring |
| Alcohol | Intensified and prolonged glucose-lowering | Major | Avoid excessive alcohol; never drink on an empty stomach; monitor blood glucose |
Major Interactions
The most clinically significant interactions involve medications that substantially alter blood glucose levels. Corticosteroids are among the most impactful, as they can raise blood glucose dramatically, sometimes necessitating a doubling of the insulin dose. Systemic corticosteroids (taken by mouth or injection) have the greatest effect, while topical or inhaled corticosteroids generally have less impact.
Beta-blockers present a particular hazard because they do not simply alter blood glucose levels but can mask the adrenergic warning signs of hypoglycaemia, such as trembling, rapid heartbeat, and anxiety. Patients taking beta-blockers may not recognise hypoglycaemia until it becomes severe. Selective beta-1 blockers (e.g., bisoprolol, metoprolol) are somewhat safer in this regard than non-selective agents (e.g., propranolol) but caution is still required.
MAO inhibitors and salicylates (high-dose aspirin) can enhance the glucose-lowering effect of insulin, increasing the risk of hypoglycaemia. If these drugs are prescribed, more frequent blood glucose monitoring is essential, and insulin dose reduction may be needed.
Minor Interactions
Several other substances can have modest effects on insulin requirements. Thyroid hormones generally increase insulin requirements, while octreotide and lanreotide (somatostatin analogues) can either increase or decrease insulin needs. Sympathomimetic agents such as salbutamol, terbutaline, and adrenaline may reduce insulin's effect. Even changes in dietary habits, herbal supplements (such as bitter melon or fenugreek), and smoking status can influence blood glucose control. Always inform your healthcare team of any changes to your medication or lifestyle.
What Is the Correct Dosage of Mixtard?
The dose of Mixtard is individualised by your doctor based on your blood glucose levels, diet, physical activity, and overall health. Typical starting doses range from 0.3 to 0.6 IU/kg/day. Mixtard is usually injected subcutaneously once or twice daily, 30 minutes before meals. Never adjust your dose without medical guidance.
Insulin dosing is one of the most individualised aspects of diabetes treatment. There is no fixed dose that works for everyone. Your doctor will determine the right dose based on your blood glucose readings, HbA1c levels, body weight, diet, physical activity level, and any other medications you are taking. The following guidelines provide general information; always follow your doctor's specific instructions.
Adults
Type 1 Diabetes
Total daily insulin requirement typically ranges from 0.5 to 1.0 IU/kg/day. When using Mixtard alone, the total daily dose is usually divided into one or two injections. Most patients require a twice-daily regimen, injecting approximately two-thirds of the total dose before breakfast and one-third before the evening meal. Some patients with stable blood glucose patterns may manage with a single daily injection.
Type 2 Diabetes
Starting doses are generally lower, typically 0.3 to 0.6 IU/kg/day, often beginning with a single daily injection of 10-20 IU before breakfast or the evening meal. The dose is then titrated upwards based on blood glucose monitoring, typically increasing by 2-4 IU every 3-7 days until target blood glucose levels are achieved. Many patients eventually require twice-daily injections.
Children
Children (aged 2 years and older)
Mixtard can be used in children aged 2 years and above. In prepubertal children, total daily insulin requirements are typically 0.5 to 1.0 IU/kg/day. During puberty, requirements often increase substantially due to hormonal changes and may reach 1.0 to 2.0 IU/kg/day. The dose should be individualised and adjusted according to the child's blood glucose levels, growth, and activity pattern. Paediatric dosing should always be supervised by a paediatric endocrinologist or diabetologist.
Elderly
Patients Over 65 Years
Insulin dose requirements in elderly patients are similar to those in younger adults, but several factors require extra attention. Reduced renal and hepatic function may slow insulin clearance, leading to prolonged insulin action and increased risk of hypoglycaemia. Elderly patients may also have reduced awareness of hypoglycaemia symptoms. More conservative dosing targets and more frequent blood glucose monitoring are often recommended. The risk of hypoglycaemia should be carefully balanced against the benefits of tight glycaemic control.
Missed Dose
If you miss a dose of Mixtard, check your blood glucose level immediately. If you realise shortly after the scheduled time and are about to eat, inject the dose as soon as possible. Do not inject a double dose to make up for a missed injection. Missing a dose may cause your blood glucose to rise (hyperglycaemia). If your blood glucose remains elevated, drink plenty of water and contact your healthcare team for advice. If you frequently miss doses, speak to your doctor about strategies to improve adherence or consider whether a different insulin regimen might suit you better.
Overdose
An overdose of insulin causes hypoglycaemia, which can range from mild (treated with oral glucose) to severe (causing unconsciousness, seizures, and potentially death if untreated). Mild hypoglycaemia: Eat glucose tablets or a sugary drink immediately, followed by a snack or meal. Severe hypoglycaemia: If the person is unconscious, do not give anything by mouth; administer glucagon injection if available and call emergency services immediately. After recovery from severe hypoglycaemia, carbohydrate intake is needed to prevent recurrence.
Mixtard is injected subcutaneously (under the skin), usually in the thigh, abdomen, upper arm, or buttock. Inject approximately 30 minutes before a meal. Always resuspend the insulin by rolling the pen between your palms or gently tipping it up and down at least 20 times until the suspension appears uniformly white and cloudy. Never use Mixtard if it remains clear, or if solid white particles stick to the bottom or wall of the container. Rotate injection sites within the same body area to reduce the risk of lipodystrophy.
What Are the Side Effects of Mixtard?
The most common side effect of Mixtard is hypoglycaemia (low blood sugar). Other possible side effects include injection site reactions, lipodystrophy (changes in fat tissue at the injection site), weight gain, and allergic reactions. Most side effects are manageable with proper technique and monitoring.
Like all medicines, Mixtard can cause side effects, although not everybody gets them. The most important side effect to be aware of is hypoglycaemia (low blood sugar), which is very common and can be life-threatening if severe. The frequency categories below follow standard medical reporting conventions based on clinical trials and post-marketing surveillance data.
Very Common (affects more than 1 in 10 people)
- Hypoglycaemia (low blood sugar) – symptoms include sweating, trembling, hunger, confusion, pallor, dizziness, palpitations. Severe episodes may cause unconsciousness or seizures
Common (affects 1 to 10 in 100 people)
- Injection site reactions – redness, swelling, itching, or pain at the injection site; usually transient
- Lipodystrophy – lumps (lipohypertrophy) or pits (lipoatrophy) under the skin at injection sites; prevented by rotating injection sites
- Weight gain – insulin promotes glucose storage as glycogen and fat; typically 2–4 kg in the first year
- Oedema – fluid retention, especially at the start of insulin therapy; usually resolves spontaneously
Uncommon (affects 1 to 10 in 1,000 people)
- Visual disturbances – temporary changes in vision, particularly during initiation of insulin therapy due to rapid changes in blood glucose; usually resolves within weeks
- Peripheral neuropathy – painful neuropathy may rarely occur with rapid improvement of blood glucose control ("insulin neuritis")
- Refraction disorders – changes in lens refraction due to altered glucose levels; these are temporary
Rare (affects fewer than 1 in 1,000 people)
- Generalised allergic reactions – skin rash over the whole body, difficulty breathing, rapid heartbeat, drop in blood pressure; may be life-threatening (anaphylaxis)
- Diabetic ketoacidosis – from insufficient insulin dosing; symptoms include nausea, vomiting, drowsiness, fruity breath odour, deep and rapid breathing
When to seek immediate medical attention
Contact your doctor or seek emergency medical help immediately if you experience any of the following:
- Severe hypoglycaemia with loss of consciousness or inability to eat or drink
- Signs of a generalised allergic reaction: widespread rash, facial swelling, difficulty breathing
- Symptoms of diabetic ketoacidosis: excessive thirst, frequent urination, nausea, vomiting, abdominal pain, fruity-smelling breath, drowsiness
- Persistent severe injection site reactions that do not resolve
If you experience any side effects not listed here, or if any side effect becomes serious, please tell your doctor, pharmacist, or diabetes nurse. You can also report side effects directly through your national adverse drug reaction reporting system, such as the Yellow Card Scheme in the UK, MedWatch in the US, or equivalent systems in other countries.
How Should You Store Mixtard?
Store unopened Mixtard in a refrigerator at 2–8°C (36–46°F). Do not freeze. Once in use, keep at room temperature (below 25°C / 77°F) for up to 6 weeks. Protect from direct heat and sunlight. Do not use if the suspension does not appear uniformly white and cloudy after resuspension.
Proper storage of insulin is essential to ensure it remains effective and safe to use. Incorrectly stored insulin may lose potency without any visible change in appearance, leading to inadequate blood glucose control. Follow these storage guidelines carefully:
- Before first use (unopened): Store in a refrigerator at 2–8°C (36–46°F). Keep in the outer carton to protect from light. Do not place next to the freezer compartment or cooling element. Do not freeze. If Mixtard has been frozen, it must not be used.
- In use (opened): Mixtard 30 FlexPen, InnoLet, and Penfill cartridges can be carried and stored at room temperature (not above 25°C / 77°F) for up to 6 weeks. Vials in use can also be kept at room temperature for up to 6 weeks. Do not refrigerate the pen you are currently using, as cold insulin injections can be more painful.
- Protect from heat and light: Do not leave Mixtard in a car, near a window, or in direct sunlight. Do not store above 30°C under any circumstances.
- When travelling: Keep Mixtard in an insulated bag. On flights, always carry insulin in your hand luggage, as cargo hold temperatures can drop below freezing. Carry a letter from your doctor confirming your need for insulin and injection supplies.
- Disposal: Do not throw insulin pens, needles, or vials in household waste. Use a sharps container and follow your local regulations for safe disposal of medical waste.
Before every injection, resuspend the insulin by gently rolling or tipping the pen/vial. The suspension should look uniformly white and cloudy. Do not use Mixtard if it appears clear, has solid particles or flakes, or has a coloured or brownish tint. These changes indicate the insulin may have degraded and may not work properly.
What Does Mixtard Contain?
Mixtard contains biphasic isophane insulin (human) as the active substance. Excipients include zinc chloride, glycerol, metacresol, phenol, disodium phosphate dihydrate, sodium hydroxide, hydrochloric acid, protamine sulphate, and water for injections.
Understanding the full composition of Mixtard is important, particularly for patients with known allergies to any pharmaceutical excipients. The active substance and all excipients are listed below:
Active substance
Biphasic isophane insulin (human, rDNA origin): Each millilitre of Mixtard 30 contains 100 IU (International Units) of human insulin. The formulation consists of 30% soluble insulin (fast-acting) and 70% isophane insulin (intermediate-acting). The insulin is produced by recombinant DNA technology in Saccharomyces cerevisiae (baker's yeast) and is structurally identical to native human insulin.
Excipients (inactive ingredients)
- Zinc chloride – stabiliser for insulin crystallisation
- Glycerol – tonicity agent to ensure the solution is isotonic with body fluids
- Metacresol – preservative (antimicrobial agent)
- Phenol – preservative (antimicrobial agent)
- Disodium phosphate dihydrate – buffer to maintain pH
- Sodium hydroxide and/or hydrochloric acid – pH adjustment
- Protamine sulphate – complexes with insulin to form the isophane (intermediate-acting) fraction; note that patients with protamine allergy may experience hypersensitivity reactions
- Water for injections – solvent
Patients with a known allergy to protamine should be aware that protamine sulphate is a key component of the isophane fraction in Mixtard. Protamine allergy is rare but can cause local or systemic hypersensitivity reactions. If you have received protamine-containing medications in the past (e.g., protamine used to reverse heparin), discuss this with your doctor before starting Mixtard.
Frequently Asked Questions About Mixtard
Mixtard 30 contains 30% soluble (fast-acting) insulin and 70% isophane (intermediate-acting) insulin, while Mixtard 50 contains 50% of each. Mixtard 30 is the most commonly prescribed ratio and provides longer-lasting basal coverage, making it suitable for most patients. Mixtard 50 has a higher proportion of fast-acting insulin, providing stronger mealtime coverage. Your doctor will choose the formulation that best matches your blood glucose pattern and eating habits.
Yes, weight gain is a common side effect of insulin therapy, including Mixtard. Insulin promotes the storage of glucose as glycogen and fat, and improved blood glucose control means less glucose is lost in urine. Most patients gain approximately 2–4 kg in the first year of insulin therapy. This can be managed through a balanced diet, regular physical activity, and careful dose optimisation with your healthcare team. The benefits of good blood glucose control far outweigh the modest weight gain.
Unopened Mixtard should be stored in a refrigerator at 2–8°C (36–46°F). Do not freeze. Once in use, Mixtard pens and cartridges can be kept at room temperature (below 25°C / 77°F) for up to 6 weeks. Always protect from direct sunlight and heat. Do not use Mixtard if it does not appear uniformly white and cloudy after gentle resuspension. When travelling, keep insulin in an insulated bag and always carry it in your hand luggage during flights.
If you miss a dose, check your blood glucose level immediately. If you realise shortly after the scheduled time and are about to eat, inject the dose as soon as possible. Do not inject a double dose to compensate. Missing a dose may cause your blood glucose to rise. If your blood glucose remains high, drink plenty of water and contact your healthcare team. If you frequently miss doses, talk to your doctor about strategies to improve adherence or whether a different insulin regimen might be more suitable.
No, you should not mix Mixtard with other insulin preparations. Mixtard is already a premixed product containing the correct ratio of soluble and isophane insulin. Mixing with other insulins could alter the pharmacokinetic profile and lead to unpredictable blood glucose control. If your doctor prescribes additional insulin (such as a rapid-acting insulin analogue for extra mealtime coverage), it should be administered as a separate injection at a different injection site.
Yes, human insulin including Mixtard can be used during pregnancy. Insulin does not cross the placenta and is considered safe for the developing baby. Maintaining good blood glucose control during pregnancy is essential to reduce risks for both mother and child, including birth defects, preeclampsia, and macrosomia. However, insulin requirements change significantly during pregnancy, so close monitoring and regular dose adjustments by your healthcare team are essential throughout pregnancy and the postpartum period.
References
- European Medicines Agency (EMA). Mixtard Summary of Product Characteristics. Available at: www.ema.europa.eu. Accessed February 2026.
- World Health Organization. WHO Model List of Essential Medicines, 23rd List, 2023. Geneva: WHO; 2023. Insulin (human) listed as an essential medicine for diabetes mellitus.
- American Diabetes Association. Standards of Care in Diabetes – 2025. Diabetes Care. 2025;48(Supplement_1):S1–S350. doi:10.2337/dc25-SINT.
- National Institute for Health and Care Excellence (NICE). Type 1 diabetes in adults: diagnosis and management [NG17]. Updated 2022. Available at: www.nice.org.uk/guidance/ng17.
- National Institute for Health and Care Excellence (NICE). Type 2 diabetes in adults: management [NG28]. Updated 2022. Available at: www.nice.org.uk/guidance/ng28.
- British National Formulary (BNF). Insulin – Biphasic isophane insulin. Available at: bnf.nice.org.uk. Accessed February 2026.
- International Diabetes Federation. IDF Diabetes Atlas, 10th edition, 2021. Available at: www.diabetesatlas.org.
- Novo Nordisk. Mixtard Prescribing Information. Available at: www.novonordisk.com.
- Hod M, et al. Insulin and insulin analogs in pregnancy: current consensus and unanswered questions. Diabetes Care. 2020;43(3):641–651.
- DeWitt DE, Hirsch IB. Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review. JAMA. 2003;289(17):2254–2264.
About Our Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, consisting of licensed physicians specialising in endocrinology, diabetology, and clinical pharmacology. Our team follows the GRADE evidence framework and adheres to guidelines from the World Health Organization (WHO), European Medicines Agency (EMA), National Institute for Health and Care Excellence (NICE), and the American Diabetes Association (ADA).
All medical claims are supported by peer-reviewed research, official drug labelling (SmPC/PI), and international clinical guidelines. Evidence level: 1A where applicable.
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