Ryzodeg FlexPen: Uses, Dosage & Side Effects
A dual-action pre-filled insulin pen combining ultra-long-acting insulin degludec (70%) with rapid-acting insulin aspart (30%) for the treatment of diabetes mellitus in adults, adolescents and children from 2 years of age.
Ryzodeg FlexPen is a soluble co-formulation of two insulin analogues delivered from a single disposable pre-filled pen. Each millilitre contains 70 units of insulin degludec, an ultra-long-acting basal insulin that provides a flat, stable glucose-lowering effect for more than 42 hours, and 30 units of insulin aspart, a rapid-acting mealtime insulin with onset within 10–20 minutes. Because the two components remain independently active after subcutaneous injection, one daily injection (or two, with the main meals) supplies both background (basal) and mealtime (prandial) insulin coverage. Ryzodeg FlexPen is used in adults, adolescents and children aged 2 years and older with type 1 or type 2 diabetes mellitus who require insulin therapy.
Quick Facts: Ryzodeg FlexPen
Key Takeaways
- Ryzodeg FlexPen is a fixed-ratio co-formulation of insulin degludec (basal) and insulin aspart (mealtime) that delivers both insulins from one injection.
- It is administered with the main meal(s) of the day, either once daily or twice daily, and offers flexibility in injection timing compared with traditional premixed insulins.
- Hypoglycaemia is the most common side effect and can be prolonged because of the long half-life of insulin degludec - always carry a source of fast-acting carbohydrate.
- The solution must be clear and colourless; never shake, mix or dilute Ryzodeg and never inject it intravenously or intramuscularly.
- Store unopened pens in the refrigerator (2–8°C); pens in use can be kept below 30°C for up to 4 weeks.
What Is Ryzodeg FlexPen and What Is It Used For?
Ryzodeg FlexPen is a prefilled, disposable insulin pen manufactured by Novo Nordisk. It is one of the first insulin products to combine two independently acting insulin analogues in a soluble co-formulation rather than a crystalline suspension. When injected into the subcutaneous tissue, insulin degludec self-assembles into soluble multi-hexamers that slowly release active insulin monomers over more than 42 hours, producing a flat, peakless basal profile. Insulin aspart, by contrast, is absorbed rapidly, reaching its peak within about one hour and covering the blood-glucose rise that follows the meal.
Because the two analogues are co-formulated, Ryzodeg FlexPen delivers simultaneous basal and prandial insulin coverage from a single injection. This is especially useful for people who would otherwise need two separate insulin injections to cover both background needs and the main meal, or for those who find multiple daily injection (MDI) regimens too complex. The product is approved for the treatment of diabetes mellitus in adults, adolescents and children from the age of 2 years.
In type 1 diabetes, where the pancreas produces little or no insulin, Ryzodeg FlexPen is usually combined with a separate rapid-acting insulin at the remaining meals of the day. In type 2 diabetes, it is typically used when oral antidiabetic medications no longer provide sufficient glycaemic control, either as monotherapy or in combination with metformin, GLP-1 receptor agonists, SGLT2 inhibitors or other oral agents. International guidelines from the American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), and the National Institute for Health and Care Excellence (NICE) support the use of premixed insulin analogues in selected patients where lifestyle, adherence or mealtime flexibility favour fewer injections.
Clinical trials, including the BOOST programme, have shown that Ryzodeg FlexPen lowers glycated haemoglobin (HbA1c) to a degree comparable with conventional premixed insulins (such as biphasic insulin aspart 30) and basal-bolus regimens, while producing fewer nocturnal hypoglycaemic events because of the flat profile of insulin degludec. The resulting glycaemic profile can improve quality of life by reducing the burden of multiple daily injections without sacrificing blood-sugar control.
Globally, diabetes affects more than 537 million adults according to the International Diabetes Federation, and the number is projected to reach 783 million by 2045. Insulin therapy remains essential for people with type 1 diabetes and many people with advanced type 2 diabetes. Premixed insulin analogues such as Ryzodeg FlexPen represent one of several modern treatment options designed to balance glycaemic efficacy, hypoglycaemia risk and patient convenience.
What Should You Know Before Taking Ryzodeg FlexPen?
Starting insulin therapy requires careful preparation. Your doctor or diabetes specialist nurse will take a full medical history, review any previous insulin regimens, check your HbA1c and fasting blood glucose, and discuss lifestyle factors such as meal patterns, physical activity, alcohol use and ability to recognise hypoglycaemia. They will also teach you injection technique, blood-glucose monitoring and how to adjust your dose.
Contraindications
You should not use Ryzodeg FlexPen if you have a known hypersensitivity to insulin degludec, insulin aspart or any of the other ingredients (glycerol, metacresol, phenol, zinc acetate, sodium chloride, hydrochloric acid, sodium hydroxide or water for injections). Signs of an allergic reaction include widespread skin rash, itching, swelling of the lips or tongue, difficulty breathing, rapid heartbeat, light-headedness and a drop in blood pressure. Severe allergic reactions (anaphylaxis) are medical emergencies requiring immediate treatment.
Ryzodeg FlexPen should not be used to treat diabetic ketoacidosis (DKA). DKA is a life-threatening complication of diabetes characterised by hyperglycaemia, dehydration, acidosis and the accumulation of ketone bodies. Treatment of DKA requires intravenous fluids and intravenous short-acting insulin in a hospital setting.
Warnings and Precautions
Several important considerations apply to the safe use of Ryzodeg FlexPen:
- Hypoglycaemia: Low blood sugar is the most frequent adverse reaction to any insulin. It can be caused by taking too much insulin, skipping a meal, unplanned vigorous exercise, alcohol consumption or drug interactions. Because insulin degludec is ultra-long-acting, severe hypoglycaemia may be prolonged and require extended monitoring.
- Hyperglycaemia: Inadequate dosing, missed injections, infection, fever, trauma, surgery, emotional stress or insulin degradation due to improper storage can cause high blood glucose. Prolonged or severe hyperglycaemia can progress to DKA (especially in type 1 diabetes) or hyperosmolar hyperglycaemic state (in type 2 diabetes).
- Skin and subcutaneous tissue changes: Repeated injections in the same spot can cause lipohypertrophy (lumpy, thickened fatty tissue), lipoatrophy (thinning of fat) or cutaneous amyloidosis. These changes can unpredictably delay or accelerate insulin absorption. Rotate injection sites within each anatomical region every injection.
- Switching insulin products: Any change in insulin type, manufacturer, concentration or species should be made under medical supervision. Dose adjustment, adjunctive therapy changes and intensified blood-glucose monitoring may be required.
- Concurrent illness: When you are unwell, your blood glucose requirements may increase substantially. Do not stop your insulin even if you cannot eat normally; instead monitor more frequently and consult your diabetes team for dose adjustment.
- Renal or hepatic impairment: Kidney or liver disease can alter insulin requirements. More frequent blood-glucose monitoring and possible dose adjustments are recommended.
- Hypoglycaemia unawareness: People with long-standing diabetes, autonomic neuropathy or frequent previous hypoglycaemia may lose the early warning symptoms. Continuous glucose monitoring (CGM) can help reduce this risk.
Insulin errors are a leading cause of medication harm. Because Ryzodeg looks similar to other clear insulin pens, always read the label carefully before each injection. Do not share your FlexPen with anyone, even if the needle is changed - this risks transmission of blood-borne viruses. Keep a spare pen in case of loss or damage.
Pregnancy and Breastfeeding
There is limited clinical experience with insulin degludec (and therefore with Ryzodeg) in pregnancy. Insulin aspart, by contrast, has been studied extensively in pregnancy and is considered safe. Because of the limited data on the degludec component, most international guidelines recommend switching to a better-studied regimen during pregnancy, typically consisting of basal insulin detemir or NPH plus a rapid-acting insulin such as aspart or lispro at meals.
If pregnancy is planned, ideally contact your diabetes team before conception to optimise blood-glucose control and adjust your insulin regimen. Tight glycaemic control before and during pregnancy reduces the risk of congenital malformations, miscarriage, pre-eclampsia, macrosomia (large-for-gestational-age baby) and neonatal hypoglycaemia. Insulin requirements typically decrease in the first trimester, rise substantially in the second and third trimesters due to placental hormones, and fall sharply after delivery.
Insulin is not known to pass into breast milk in clinically significant amounts because, even if it did, it would be broken down in the infant's digestive tract. However, insulin requirements may change during breastfeeding and dietary intake should be adjusted to avoid hypoglycaemia. Discuss any change of insulin regimen with your diabetes team before delivery.
Use in Children and Adolescents
Ryzodeg FlexPen is approved for use in children from the age of 2 years. Dosing must be individualised by a paediatric endocrinologist based on age, weight, pubertal stage, blood-glucose profile and activity patterns. Parents and caregivers must be trained in injection technique, blood-glucose monitoring, carbohydrate counting and hypoglycaemia management. Children's insulin requirements typically change during growth spurts and puberty; regular review is essential.
Driving and Operating Machinery
Your ability to concentrate and react may be impaired during episodes of hypoglycaemia or hyperglycaemia. This can be a safety issue in situations such as driving, operating machinery or working at heights. Always check your blood glucose before driving, especially for long journeys, and keep fast-acting carbohydrate within reach. Do not drive if your blood glucose is below 5 mmol/L (90 mg/dL). Inform your driver-licensing authority of your diabetes and insulin treatment as required by local regulations.
How Does Ryzodeg FlexPen Interact with Other Drugs?
Insulin interacts with a wide range of medications, either pharmacodynamically (by altering blood glucose) or through changes in insulin sensitivity. The effect can be additive, opposing or unpredictable depending on the dose, duration of treatment and individual patient factors. Monitoring blood glucose more frequently is recommended whenever any of the following drugs are started, stopped or dose-adjusted.
Major Interactions - Drugs That Increase Hypoglycaemia Risk
The following medications can potentiate the blood-glucose-lowering effect of Ryzodeg FlexPen and may require a reduction in insulin dose:
| Drug / Class | Typical Use | Interaction Mechanism |
|---|---|---|
| Oral antidiabetic agents (sulphonylureas, meglitinides) | Type 2 diabetes | Additive glucose-lowering effect; stimulate endogenous insulin secretion |
| GLP-1 receptor agonists (liraglutide, semaglutide) | Type 2 diabetes, obesity | Glucose-dependent insulin secretion; delayed gastric emptying |
| ACE inhibitors (enalapril, ramipril, lisinopril) | Hypertension, heart failure | Increase insulin sensitivity; risk greatest at initiation |
| MAO inhibitors (phenelzine, tranylcypromine) | Resistant depression | Enhance insulin effect and impair counter-regulatory response |
| Salicylates (high-dose aspirin) | Pain, inflammation | Enhance peripheral glucose utilisation and reduce hepatic glucose output |
| Anabolic steroids (testosterone, nandrolone) | Hormone replacement, muscle wasting | Increase insulin sensitivity |
| Sulphonamides (co-trimoxazole) | Infections | Displace sulphonylureas from binding and enhance insulin effect |
| Pentamidine | Pneumocystis pneumonia | Beta-cell toxicity may cause hypoglycaemia then hyperglycaemia |
| Disopyramide | Arrhythmias | Stimulates insulin secretion |
| Fluoxetine and other SSRIs | Depression, anxiety | Improve insulin sensitivity; weight effects may lower glucose |
Major Interactions - Drugs That Decrease Insulin Effectiveness
The following medications can reduce the effect of insulin and may require an increase in insulin dose:
| Drug / Class | Typical Use | Interaction Mechanism |
|---|---|---|
| Corticosteroids (prednisolone, dexamethasone) | Inflammation, autoimmune disease | Increase hepatic glucose output and insulin resistance |
| Oral contraceptives (combined) | Contraception, menstrual regulation | Oestrogen-related increase in insulin resistance |
| Thiazide diuretics (bendroflumethiazide, hydrochlorothiazide) | Hypertension, oedema | Impair insulin secretion; potassium depletion |
| Sympathomimetics (salbutamol, terbutaline, adrenaline) | Asthma, anaphylaxis | Stimulate glycogenolysis and gluconeogenesis |
| Growth hormone (somatropin) | Growth hormone deficiency | Counter-regulatory to insulin |
| Thyroid hormones (levothyroxine) | Hypothyroidism | Increase glucose absorption and metabolism |
| Danazol | Endometriosis | Causes insulin resistance |
| Atypical antipsychotics (olanzapine, clozapine) | Schizophrenia, bipolar disorder | Weight gain and insulin resistance |
| Protease inhibitors (ritonavir) | HIV infection | Cause insulin resistance and lipodystrophy |
Minor or Variable Interactions
Beta-blockers (propranolol, atenolol, metoprolol) deserve special mention. While non-selective beta-blockers can slightly prolong hypoglycaemia, their more important effect is masking the adrenergic warning symptoms of hypoglycaemia (tremor, tachycardia, palpitations). People taking beta-blockers may therefore experience severe hypoglycaemia without the usual warning signs. Cardio-selective beta-blockers such as bisoprolol are less likely to cause this problem.
Octreotide and lanreotide (somatostatin analogues used for acromegaly and neuroendocrine tumours) may either decrease or increase insulin requirements. Pioglitazone, when combined with insulin, has been associated with heart failure in patients with pre-existing cardiac disease - inform your doctor if you are prescribed both. Alcohol can both enhance and weaken the glucose-lowering effect of insulin; notably, alcohol can cause severe hypoglycaemia up to 24 hours after consumption, especially if drunk without food.
Always share a full list of prescription medicines, over-the-counter drugs and herbal or dietary supplements with your healthcare team. Do not start or stop any medication without discussing the impact on your blood glucose. Minor changes, such as dose adjustment of a diuretic or steroid course for an illness, often require temporary insulin dose adjustments.
What Is the Correct Dosage of Ryzodeg FlexPen?
The dose of Ryzodeg FlexPen is highly individualised. It depends on the type of diabetes, body weight, diet, level of physical activity, concurrent medications and glycaemic targets set by your diabetes team. The ultimate aim is to achieve HbA1c and glucose targets while minimising hypoglycaemia. Dose adjustments are normally made in small increments (1–4 units) every 3–7 days based on self-monitored fasting and pre-meal blood glucose readings.
Adults
People with Type 2 Diabetes - Insulin-Naive
The usual recommended starting dose is 10 units with the main meal of the day, followed by individual dose adjustments. When used with oral antidiabetic agents, the dose is titrated by 2–4 units every 3–4 days based on fasting blood glucose until the target is reached (typically 4–7 mmol/L or 70–130 mg/dL before breakfast).
People Switching from Once-Daily Basal Insulin
Convert unit-for-unit to once-daily Ryzodeg FlexPen given with the main meal. Blood-glucose monitoring should be intensified during the switching period, and the dose titrated thereafter based on response. Close follow-up in the first 1–2 weeks is recommended.
People Switching from Premixed or Self-Mixed Insulin (Twice-Daily Regimen)
Convert unit-for-unit on a total daily dose basis, distributing Ryzodeg 50:50 between breakfast and the evening meal, or 50% at breakfast and 50% at the main evening meal. Adjustment may be needed in the following weeks based on individual response.
People with Type 1 Diabetes
Ryzodeg FlexPen is usually given once or twice daily with the main meal(s), with additional rapid-acting insulin (e.g. insulin aspart) at the remaining meals. The recommended starting dose is 60–70% of the previous total daily insulin requirement, administered as Ryzodeg at the main meal, with the remainder given as rapid-acting insulin at the other meals. Individualise based on glucose response.
Children and Adolescents (2-17 years)
Paediatric Dosing
Ryzodeg FlexPen can be used in children from 2 years of age. The starting dose and titration schedule must be determined by a paediatric endocrinologist and individualised to the child's age, weight, diet, physical activity and the remainder of the insulin regimen. For paediatric type 1 diabetes, it is used as part of a basal-bolus regimen with a rapid-acting insulin at meals not covered by Ryzodeg. Close parental supervision of injection technique, blood-glucose monitoring and hypoglycaemia management is essential.
Elderly Patients (65+ years)
Older Adults
Ryzodeg FlexPen can be used in older adults. Glycaemic targets are often less strict in frail elderly patients to reduce the risk of hypoglycaemia, which is associated with falls, cognitive decline and cardiovascular events. Because renal function often declines with age, insulin clearance may be reduced, potentially lowering insulin requirements. Careful titration and more intensive monitoring are recommended, especially in those with reduced awareness of hypoglycaemia.
Renal or Hepatic Impairment
Special Populations
Ryzodeg can be used in patients with renal or hepatic impairment, but insulin requirements may be reduced in advanced disease. More frequent blood-glucose monitoring and individual dose adjustment are required. No specific dose-adjustment protocol applies - titrate based on glucose response.
Injection Technique
Ryzodeg FlexPen is administered by subcutaneous injection only. It should never be injected intravenously or intramuscularly because this would profoundly alter the pharmacokinetics of both components and could cause severe hypoglycaemia. It is also not intended for use in continuous subcutaneous insulin infusion (insulin pumps).
The preferred injection sites are:
- Anterior abdominal wall - usually the fastest and most consistent absorption; avoid a 5 cm radius around the navel.
- Upper front of the thigh - slightly slower absorption; useful for evening injections.
- Upper arm (outer aspect) - suitable when self-injection is supervised by another person.
Rotate injection sites within the same anatomical region each time to prevent lipohypertrophy and inconsistent insulin absorption. Inspect the solution before every injection - it must be clear and colourless. Do not use the pen if the insulin appears cloudy, discoloured or contains visible particles.
Ryzodeg FlexPen must never be diluted or mixed with any other insulin product or intravenous fluid. Doing so alters the pharmacokinetic profile and can cause unpredictable hypo- or hyperglycaemia. Each pen is intended for single-patient use only - never share your pen or needles, even with the needle changed, as this risks transmission of blood-borne viruses such as hepatitis B, hepatitis C and HIV.
Missed Dose
If you forget to take your Ryzodeg FlexPen dose, take it as soon as you remember with a meal. If you only notice the missed dose at the next scheduled injection time, skip the missed dose and continue with your normal schedule - do not take a double dose. Check your blood glucose more frequently for the next 24 hours, and if you are unsure what to do, contact your diabetes team. Consistency of injection timing improves glucose control but occasional flexibility of up to 8 hours is acceptable because of the long half-life of insulin degludec.
Overdose
Insulin overdose causes hypoglycaemia which can be life-threatening. Mild to moderate hypoglycaemia can usually be treated with oral glucose or carbohydrate-containing foods. For severe hypoglycaemia with loss of consciousness or inability to swallow, intramuscular or subcutaneous glucagon (0.5–1 mg) should be administered by a trained family member or friend, followed by emergency medical care. Intravenous glucose (e.g. 20% dextrose) should be given by healthcare professionals. Because insulin degludec is ultra-long-acting, prolonged monitoring and repeated carbohydrate intake may be required for several hours to prevent recurrent hypoglycaemia.
Stopping insulin abruptly, especially in type 1 diabetes, can cause diabetic ketoacidosis (DKA) within hours - a life-threatening emergency with nausea, vomiting, abdominal pain, deep rapid breathing, ketone breath and drowsiness. Never stop or reduce your insulin without speaking to your diabetes team. During illness, sick-day rules apply: continue insulin, monitor blood glucose and ketones frequently, maintain hydration and contact a healthcare professional if vomiting or ketones persist.
What Are the Side Effects of Ryzodeg FlexPen?
Like all insulin products, Ryzodeg FlexPen can cause side effects, although not everyone gets them. Understanding the likelihood and nature of these reactions helps you recognise them early and seek appropriate care. The frequencies below follow the conventions used in the European Union Summary of Product Characteristics.
Very Common
May affect more than 1 in 10 people
- Hypoglycaemia (low blood sugar) - the most frequent adverse reaction. Warning symptoms include sweating, pale skin, tremor, rapid heartbeat, palpitations, hunger, nervousness, headache and difficulty concentrating. Severe hypoglycaemia can lead to confusion, seizures, unconsciousness and can be fatal if untreated.
Common
May affect up to 1 in 10 people
- Injection-site reactions - pain, redness, bruising, swelling, bleeding or itching at the injection site. Usually mild and resolves within a few days.
- Lipohypertrophy - thickening of the fatty tissue caused by repeated injections in the same area. Can impair insulin absorption.
- Peripheral oedema - mild fluid retention, particularly at the start of insulin treatment or when glycaemic control rapidly improves. Usually self-limiting.
Uncommon
May affect up to 1 in 100 people
- Hypersensitivity reactions - skin rash, itching, hives (urticaria) or swelling of the skin.
- Lipoatrophy - thinning of the fat tissue at injection sites, preventable by rotating sites consistently.
Rare
May affect up to 1 in 1,000 people
- Anaphylaxis (severe allergic reaction) - widespread rash, pronounced skin or mucosal swelling, wheezing, severe breathing difficulty, drop in blood pressure and collapse. This is a medical emergency - call emergency services immediately.
- Visual disturbances - blurred vision during rapid glycaemic improvement or worsening, usually transient.
- Diabetic retinopathy progression - rapid improvement in blood-glucose control can be associated with temporary worsening of retinopathy; long-term good control is protective.
Very Rare / Frequency Not Known
Post-marketing reports
- Cutaneous amyloidosis - lumps under the skin caused by amyloid protein deposition at repeatedly used injection sites. Can impair insulin absorption. Frequency is not precisely known.
- Painful peripheral neuropathy - acute, reversible painful neuropathy may occur when long-standing poor glycaemic control improves rapidly.
Side Effects in Children and Adolescents
The safety profile of Ryzodeg FlexPen in children and adolescents aged 2–18 years is broadly similar to that in adults. Injection-site reactions and mild skin reactions appear to be reported slightly more often in younger patients. Clinical experience with insulin degludec in children under 2 years of age is limited.
Some people with type 2 diabetes and long-standing heart disease or a history of stroke who were treated with both pioglitazone (an oral antidiabetic medicine) and insulin have developed heart failure. Tell your doctor immediately if you notice signs of heart failure such as increasing shortness of breath, swelling of the ankles or feet, or rapid unexplained weight gain.
Recognising and Managing Hypoglycaemia
Because hypoglycaemia is the most common and most important side effect of Ryzodeg FlexPen, every person using it must be able to recognise and treat it. Symptoms typically appear when blood glucose falls below 4 mmol/L (70 mg/dL).
Step 1: Stop whatever you are doing and sit down. Consume 15–20 g of fast-acting carbohydrate - for example, 4-5 glucose tablets, a small glass (150 ml) of fruit juice or sugar-sweetened soft drink, a tablespoon of honey, or 3 heaped teaspoons of sugar dissolved in water. Diet drinks and artificial sweeteners do NOT help.
Step 2: Wait 15 minutes, then recheck your blood glucose. If still below 4 mmol/L (70 mg/dL), repeat step 1.
Step 3: Once blood glucose has recovered, eat a longer-acting carbohydrate (a slice of bread, a sandwich or biscuits) to prevent rebound hypoglycaemia. Because insulin degludec is long-acting, recovery may need to be sustained over several hours.
If the person is unconscious: Do NOT give food or drink. Call emergency services. A relative or friend trained in glucagon use should give intramuscular or subcutaneous glucagon. Place the person in the recovery position and stay with them until help arrives.
Recognising and Managing Hyperglycaemia
Hyperglycaemia (high blood sugar) can occur if Ryzodeg doses are too low, missed or delivered incorrectly, if the insulin has been stored improperly, or during illness, infection, stress or surgery. Early symptoms include increased thirst, frequent urination, dry mouth, fatigue and blurred vision. Without treatment, hyperglycaemia can progress to diabetic ketoacidosis (DKA), especially in type 1 diabetes, with nausea, vomiting, abdominal pain, deep rapid breathing, acetone-smelling breath and drowsiness. If you suspect DKA, check blood or urine ketones and seek urgent medical attention.
How Should You Store Ryzodeg FlexPen?
Correct storage is essential for maintaining the potency and safety of Ryzodeg FlexPen. Insulin that has been frozen, overheated or exposed to direct sunlight can lose its activity without any visible change, resulting in unexpectedly high blood glucose. Follow the storage conditions below to keep your insulin safe and effective.
Unopened Pens (Not Yet in Use)
- Store in a refrigerator at 2–8°C.
- Do not freeze. Frozen insulin is permanently inactivated and must be discarded.
- Keep away from the cooling element of the refrigerator (usually the rear wall).
- Keep the pen cap on to protect from light.
- Do not use Ryzodeg after the expiry date printed on the label and carton - the expiry date refers to the last day of the stated month.
Pens in Use or Carried as a Spare
- Once first opened, the pen can be stored for up to 4 weeks.
- Store at a temperature below 30°C, or in a refrigerator (2–8°C) away from the cooling element.
- Keep the pen cap on when not in use to protect from light.
- Never store with the needle attached, as this can cause leakage of insulin or entry of air and bacteria into the cartridge.
- Write the date of first use on the pen label to track the 4-week window.
- Discard the pen after 4 weeks of use even if insulin remains - its potency and sterility can no longer be guaranteed.
Before each injection, inspect the solution in the cartridge. Ryzodeg must be clear and colourless, like water. Do not use the pen if the solution is cloudy, discoloured or contains visible particles, or if the pen has been dropped on a hard surface or shows signs of damage - retain the pen and consult your pharmacy for replacement and disposal.
Keep Ryzodeg FlexPen and all medicines out of sight and reach of children. Do not dispose of used pens or needles via household waste or sewage. Return used pens to your pharmacy or use an approved sharps container for needle disposal according to local regulations - this protects other people and the environment.
When travelling, keep your insulin in your carry-on luggage; checked baggage in aircraft holds can reach freezing temperatures. Use an insulated cooling wallet in hot climates, but ensure the insulin does not come into direct contact with ice or cold packs. Carry a letter from your doctor describing your need for insulin and injection devices if crossing borders, and take at least 50% more supplies than you expect to need in case of delays.
What Does Ryzodeg FlexPen Contain?
Active Ingredients
Ryzodeg FlexPen contains two insulin analogues in a fixed ratio. Each millilitre contains 100 units of total insulin, of which 70 units (70%) are insulin degludec and 30 units (30%) are insulin aspart. A standard 3 ml pre-filled pen therefore delivers 300 units in total. Both components are produced by recombinant DNA technology in the yeast Saccharomyces cerevisiae.
Insulin degludec differs from human insulin by a single amino acid removal (threonine at position B30) and the attachment of a 16-carbon fatty diacid (hexadecanedioic acid) via a glutamic acid spacer. These modifications allow the insulin to form long, soluble multi-hexamer chains at the injection site, from which single monomers dissociate slowly into the circulation, giving a flat, stable action that lasts more than 42 hours.
Insulin aspart differs from human insulin by a single amino acid substitution - proline at position B28 is replaced by aspartic acid. This change weakens the natural tendency of insulin molecules to form hexamers, allowing rapid absorption after subcutaneous injection. Insulin aspart begins to lower blood glucose within 10–20 minutes, peaks around 1–3 hours and lasts about 3–5 hours.
Inactive Ingredients (Excipients)
| Ingredient | Purpose |
|---|---|
| Glycerol | Tonicity agent (makes the solution isotonic with blood) |
| Metacresol | Preservative and stabiliser |
| Phenol | Preservative and stabiliser of insulin hexamers |
| Zinc acetate | Stabilises insulin multi-hexamer structures |
| Sodium chloride | Tonicity adjustment |
| Hydrochloric acid | pH adjustment |
| Sodium hydroxide | pH adjustment |
| Water for injections | Solvent |
Ryzodeg FlexPen contains less than 1 mmol (23 mg) of sodium per dose, which means it is essentially sodium-free. This is useful for people on a controlled sodium diet.
Available Form and Pack Size
Ryzodeg FlexPen is supplied as a clear, colourless solution for injection in a disposable pre-filled pen:
- Strength: 100 units/ml (70 units insulin degludec + 30 units insulin aspart per ml).
- Pen volume: 3 ml cartridge (300 total units per pen).
- Dose range: 1 to 80 units per injection, in 1-unit increments.
- Pack sizes: 1, 5 or 10 pre-filled pens (availability varies by country).
The pen is designed for use with NovoFine or NovoTwist disposable needles of up to 8 mm in length. Always use a new needle for each injection. Not all pack sizes may be marketed in all countries.
Frequently Asked Questions About Ryzodeg FlexPen
Unlike traditional premixed insulins such as NovoMix 30 or Humalog Mix 25, which are cloudy suspensions containing protamine-crystallised insulin that must be resuspended before every injection, Ryzodeg FlexPen is a clear, soluble co-formulation. The two components - insulin degludec (70%) and insulin aspart (30%) - remain independently active after injection. Insulin degludec provides ultra-long basal coverage beyond 42 hours, while insulin aspart covers the meal. This means Ryzodeg can be given with flexible timing at the main meal of the day, and the basal component does not peak or need to be resuspended. The overall effect is a flatter basal profile with fewer nocturnal hypoglycaemic episodes.
Yes, but switching should always be done under medical supervision. When changing from premixed, self-mixed or basal insulin to Ryzodeg, a dose and timing adjustment is usually required. A common starting approach for people previously on once-daily basal insulin is to convert unit-for-unit to once-daily Ryzodeg given with the main meal. For those on twice-daily premixed insulin, the total daily dose is often divided 50:50 between breakfast and the evening meal, though this must be individualised. Close blood-glucose monitoring and dose titration over several days to weeks are essential after switching. Expect minor dose adjustments as the body adapts to the new insulin profile.
Ryzodeg FlexPen should be injected with the main meal(s) of the day. It can be administered immediately before the meal or, if needed, shortly after starting the meal. Unlike human premixed insulin, which must be given 30 minutes before eating, the rapid-acting insulin aspart component of Ryzodeg allows for mealtime or immediately post-meal administration. This flexibility is particularly useful for people with unpredictable appetite, shift workers and elderly patients where meal size may vary. Try to keep injection timing reasonably consistent from day to day, but an occasional 2–4 hour shift is acceptable because of the ultra-long-acting degludec component.
Clinical experience with insulin degludec in pregnancy is limited, and Ryzodeg FlexPen is generally not recommended during pregnancy or breastfeeding. Most international guidelines, including those from NICE, recommend switching to better-studied insulins during pregnancy - typically isophane (NPH) or insulin detemir for basal coverage, and insulin aspart or regular human insulin for meals. If pregnancy is planned or confirmed, speak to your diabetes team as early as possible to review your insulin regimen. Good blood-glucose control before and during pregnancy is crucial to reduce the risk of miscarriage, congenital malformations, pre-eclampsia and neonatal hypoglycaemia.
Unopened Ryzodeg FlexPen should be stored in a refrigerator at 2–8°C, away from the cooling element. Do not freeze. Keep the pen cap on to protect from light. Once in use (or kept at room temperature as a back-up), the pen can be stored for up to 4 weeks at temperatures below 30°C. Do not refrigerate again once the pen has been stored at room temperature. Always replace the pen cap after use and never store the pen with the needle attached, as this can let insulin leak out or air bubbles enter the cartridge. Discard the pen after 4 weeks of first use, even if insulin remains.
At the first sign of hypoglycaemia - sweating, shakiness, hunger, palpitations, confusion or blurred vision - immediately consume 15–20 grams of fast-acting carbohydrate, such as four glucose tablets, a small glass (150 ml) of non-diet fruit juice, or a tablespoon of honey. Recheck your blood glucose after 15 minutes and repeat if still below 4 mmol/L (70 mg/dL). Follow with a longer-acting carbohydrate such as a slice of bread or biscuits to prevent recurrence. Because insulin degludec is ultra-long-acting, hypoglycaemia may be prolonged and you should monitor blood glucose for several hours. If you lose consciousness, a relative or friend trained in glucagon administration should give an intramuscular or subcutaneous glucagon injection and call emergency services immediately.
Yes, Ryzodeg FlexPen is approved for use in children from 2 years of age with type 1 or type 2 diabetes. Paediatric dosing must be determined by a paediatric endocrinologist and individualised to the child's age, weight, pubertal stage, diet and activity pattern. For most children with type 1 diabetes it is used as part of a basal-bolus regimen, with a separate rapid-acting insulin given at meals not covered by Ryzodeg. Parents and caregivers must be trained in injection technique, blood-glucose monitoring and hypoglycaemia management. Clinical experience below 2 years of age is limited.
References
- European Medicines Agency. Ryzodeg - Summary of Product Characteristics. EMA; 2024. Official European prescribing information for insulin degludec/insulin aspart 70/30.
- U.S. Food and Drug Administration. Ryzodeg 70/30 (Insulin Degludec and Insulin Aspart Injection) - Prescribing Information. FDA; 2024. Official U.S. prescribing information.
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