insulin degludec

Insulin degludec is a type of insulin used to improve glycemic control in adults and children one year or older with diabetes mellitus type I or II. Insulin degludec is a biological product, manufactured in the lab using recombinant DNA technology. Insulin degludec is a structurally similar analog to the human insulin, a natural hormone produced by the pancreas. Insulin degludec is a long-acting basal insulin taken once daily to maintain blood sugar levels at times other than the glucose surges that occur with meal intake.

Insulin is released by the pancreas after a meal to regulate the metabolism of carbohydrates, fats and proteins absorbed from food. Diabetes is a metabolic disorder with high blood glucose levels (hyperglycemia), caused by insulin dysfunction which impairs the ability of cells to absorb glucose for energy. Diabetes affects the entire body and can damage all organs, particularly, nerves, kidneys and eyes.

Type I diabetes is a genetic autoimmune condition in which the immune cells destroy the insulin-producing cells in the pancreas, resulting in little or complete absence of insulin secretion. Type I diabetes develops typically in adolescence. Type II diabetes is more common and is mostly related to lifestyle, and develops later in life because the pancreas produces less insulin, or the body becomes resistant to insulin.

Insulin degludec provides the insulin the body requires for regulating glucose metabolism and maintaining optimal glucose levels. Insulin reduces blood glucose by stimulating the uptake of glucose from blood into the organs and tissues, particularly skeletal muscle, fat cells and the liver. Insulin inhibits glucose production in the liver, inhibits breakdown of fats and proteins, and enhances protein synthesis. 

Insulin degludec is administered as a subcutaneous injection into the skin with a needle and syringe or a prefilled pen. Insulin degludec takes effect in 30 to 90 minutes, and is slowly released, with peak effects at 9 hours and effects lasting for 24 hours. The long action of insulin degludec is primarily due to delayed systemic absorption from the subcutaneous tissue. Insulin degludec should not be used to treat diabetic ketoacidosis, a serious complication of diabetes that requires emergency medical treatment.

• Do not administer insulin degludec in patients:
  • During episodes of low blood glucose (hypoglycemia)
  • With hypersensitivity to any component of insulin degludec
• Train patients to self-administer insulin degludec injections with needles and syringes or prefilled pens and advise them to never share the delivery devices, in order to prevent transmission of bloodborne infections.
• Changes in insulin type, strength, manufacturer, or mode of administration can affect glycemic control and cause hyperglycemia or hypoglycemia. Insulin regimen changes should be made under close medical supervision with increased frequency of blood glucose monitoring. Patients with type II diabetes may require concomitant anti-diabetic treatment.
• Repeated insulin injections into the same areas can cause skin thickening or depression (lipodystrophy) or abnormal protein clumping in the skin (cutaneous amyloidosis). Injecting in these areas can reduce insulin absorption and result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) may result in hypoglycemia. Advise patients to rotate injection sites regularly.
• Hypoglycemia is the most common adverse effect with all insulin therapies, including insulin degludec. Recovery from hypoglycemia may take longer with long-acting insulins such as insulin degludec than with short-acting insulins.
  • Hypoglycemia can affect concentration ability and reaction time and put the patient and others at risk when engaging in hazardous activities.
  • Severe hypoglycemia can cause seizure, unconsciousness, temporary or permanent brain damage, and even death.
  • Patients with long-standing diabetes, diabetic nerve disease (neuropathy), recurrent hypoglycemia, or patients taking beta-blockers may have reduced awareness of hypoglycemic symptoms.
  • Hypoglycemia can happen suddenly and symptoms differ in patients and may change over time in the same patient.
  • Risk of hypoglycemia is related to the insulin product’s duration of action and is highest at the time of its peak effect.
  • Changes in meal pattern, physical activity and concomitant medications can increase the risk for hypoglycemia.
  • Impairment of liver or kidney function increases the risk for hypoglycemia.
  • Blood glucose monitoring should be performed more frequently in patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia.
  • Patients and caregivers must be educated to self-monitor glucose levels, recognize and manage hypoglycemia.
• Insulin degludec can cause severe, life-threatening, generalized allergic reactions including anaphylaxis. Discontinue insulin degludec in patients who develop allergic reactions, treat appropriately and monitor until symptoms resolve. Do not use in patients who have had previous hypersensitivity reactions to insulin degludec.
• All insulins, including insulin degludec cause shift of potassium into the cells that can lead to low potassium (hypokalemia), which, if untreated, can cause respiratory paralysis and life-threatening irregular ventricular rhythm (ventricular arrhythmia) and death. Monitor potassium levels in patients at risk for hypokalemia, including patients taking potassium-lowering medications or medications sensitive to potassium concentrations.
• Concurrent use of insulin degludec with thiazolidinediones, a class of oral antidiabetic drugs known as peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention and increase the risk for heart failure. Closely monitor such patients for symptoms and if patient develops heart failure, treat appropriately and consider discontinuation or dose reduction of PPAR-gamma agonist.

Common side effects of insulin degludec include:

• Hypoglycemia
• Nose and throat inflammation (nasopharyngitis)
• Upper respiratory infection
• Headache
• Sinus inflammation (sinusitis)
• Gastroenteritis
• Diarrhea
• Hypersensitivity reactions including:
  • Generalized allergy
  • Generalized skin reactions
  • Severe allergic reactions (anaphylaxis)
  • Swelling in subcutaneous and mucous tissue (angioedema)
  • Drop in blood pressure (hypotension)
  • Bronchospasm
  • Shock
  • Swelling of tongue and lips
  • Nausea
  • Diarrhea
  • Tiredness
  • Hives (urticaria)
  • Itching (pruritus)
• Injection site reactions such as:
  • Hematoma
  • Hemorrhage
  • Redness (erythema)
  • Pain
  • Nodules
  • Swelling
  • Discoloration
  • Itching (pruritus)
  • Warmth
  • Mass
• Fat tissue changes (lipodystrophy) with long-term repeated injections including:
  • Wasting of skin tissue (lipoatrophy)
  • Thickening of skin tissue (lipohypertrophy)
• Localized collection of abnormal proteins (cutaneous amyloidosis) with repeated injections
• Hyperglycemia with repeated injections into areas of cutaneous amyloidosis
• Weight gain
• Swelling of extremities from fluid retention (peripheral edema)
• Development of anti-insulin antibodies

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Injectable solution (prefilled pen, FlexTouch)

• 100 units/mL
• 200 units/mL

Adult:

Type 1 Diabetes Mellitus

• Long-acting basal insulin indicated to improve glycemic control in patients with diabetes mellitus

Initial dose

• For insulin-naive patients
  • Start approximately 1/3 to 1/2 of the total daily insulin dose; use remaining of total daily insulin dose on short-acting insulin and divided between each daily meal
  • Usual initial dose range: 0.2-0.4 units/kg

Type 2 Diabetes Mellitus

• Long-acting basal insulin indicated to improve glycemic control in adults with type 2 diabetes mellitus

Initial dose

• For insulin-naive patients
• Start 10 units subcutaneous (SC) once daily

Dosage Modifications

Hepatic impairment

• No difference in the pharmacokinetics of insulin degludec was identified in a study comparing healthy subjects and subjects with hepatic impairment (mild, moderate, and severe hepatic impairment)

Renal impairment

• No clinically relevant difference in the pharmacokinetics of insulin degludec was identified in a study comparing healthy subjects and subjects with renal impairment including subjects with end stage renal disease

Dosing Considerations

• Use insulin degludec with caution in patients with visual impairment that may rely on audible clicks to dial their dose

Starting dose in patients already on insulin therapy

• Type 1 or 2 diabetes mellitus: Start insulin degludec at the same unit dose as the total daily long or intermediate-acting insulin unit dose

Limitation of use

• Not indicated for diabetic ketoacidosis

Pediatric:

Type 1 Diabetes Mellitus

Long-acting basal insulin indicated to improve glycemic control in children and adolescents aged 1-17 years with type 1 diabetes mellitus

Children below 1 year

• Safety and efficacy not established

Children and adolescents aged 1-17 years

• Starting dose in insulin naive patients
  • Start approximately 1/3 to 1/2 of the total daily insulin dose; use remaining of total daily insulin dose on short-acting insulin and divided between each daily meal
  • Usual initial dose range: 0.2-0.4 units/kg

Type 2 Diabetes Mellitus

Long-acting basal insulin indicated to improve glycemic control in children and adolescents aged 1-17 years with type 2 diabetes mellitus

Children below 1 year

• Safety and efficacy not established

Children and adolescents aged 1-17 years

• Starting dose in insulin naive patients
  • 10 units SC once daily

Dosing Considerations

Limitations of use

• Not indicated for diabetic ketoacidosis
• Not recommended for pediatric patients requiring less than 5 units of insulin degludec

Overdose

• Insulin degludec overdose relative to food intake, energy expenditure or both can cause severe hypoglycemia and hypokalemia.
• Mild hypoglycemia can be treated with oral glucose and appropriate adjustments in drug dosage, meal patterns and exercise, as required.
• Severe hypoglycemic episodes with coma, seizure or neurologic impairment may be treated with concentrated intravenous glucose or intramuscular or subcutaneous injection of glucagon. Additional carbohydrate intake and monitoring of the patient may be required to prevent recurrence of hypoglycemia.
• Hypokalemia should be corrected with appropriate supplemental potassium.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Insulin degludec has no listed severe interactions with other drugs.
• Serious interactions of insulin degludec include:
  • ethanol
  • macimorelin
• Insulin degludec has moderate interactions with at least 180 different drugs.
• Mild interactions of insulin degludec include:
  • stevia

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Available information on the use of insulin degludec during pregnancy has not identified a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.
• Women with pre-gestational diabetes have hyperglycemic and hypoglycemic episodes more often during pregnancy. Good glycemic control before conception and throughout pregnancy is essential for maternal and fetal health.
• Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery complications, and fetal risks for birth defects and abnormally large growth (macrosomia).
• There is no information on the presence of insulin degludec in breastmilk, or its effects on milk production or the breastfed infant. Insulin degludec is present in rat milk.
• Decision to breastfeed during treatment with insulin degludec should be based on the mother’s clinical need for the drug, the developmental and health benefits of breastfeeding and potential risks to the breastfed infant from exposure to the drug or mother’s underlying condition.

• Never share your pen, needles, or syringes with others, or use those used by others.
• Always check labels before every injection to avoid errors of mix-up with other insulin products.
• Do not transfer insulin degludec from the pen into a syringe, the syringe markings will not be a correct measure and can result in overdose and hypoglycemia.
• Administer your insulin degludec injections exactly as prescribed, any regimen change must be done only under your physician’s supervision.
• Rotate your injection sites and do not inject into areas of skin that have scars, pits, lumps, scales, or are tender or bruised.
• Learn to monitor glucose levels and to recognize symptoms of hypoglycemia. Always carry sweets such as hard candy for immediate use and seek medical help if symptoms don’t resolve.
• Report to your physician immediately if you experience any allergic reaction to insulin degludec.
• Avoid alcohol, it can have an additive effect and increase the risk for hypoglycemia.
• Hypoglycemia can impair concentration ability and reaction time, be cautious about activities such as driving and operating heavy machinery.
• Store your insulin degludec delivery devices safely out of reach of children.
• In case of overdose, seek medical help immediately or call Poison Control.