Insulin Degludec (Tresiba) is long-acting insulin with a half-life elimination of about 25 hours. Compared to Insulin glargine and insulin detemir, other long-acting insulin formulations, it may be administered as a once-daily injection at any time of the day. It is used for the treatment of hyperglycemia in patients aged one year or older with type-1 or type-2 diabetes mellitus.

Insulin Degludec Dose in Adults

Insulin Degludec Dose in the treatment of type 1 Diabetes mellitus: 

Note:

• Patients with type 1 Diabetes mellitus should be advised insulin Degludec as basal insulin and rapid or short-acting insulins as prandial insulins (multiple daily injections are required).
• The total daily doses (TDD) presented below are expressed as the total units/kg/day of all insulin formulations combined.

Insulin Degludec General insulin dosing:

• Initial TDD (total daily dose):
  • 0.2 - 0.4 units /kg/day initially to avoid hypoglycemia. The dose is adjusted according to the blood glucose levels.
  • Obese patients may be initiated at a dose of about 0.4 - 0.5 units/kg/day.
• The usual maintenance (total daily dose) ranges between 0.4 - 1 unit/kg/day that is administered in divided doses.

The total daily dose may be divided into multiple daily injections as follows:

• Basal insulin (insulin degludec):

  • 40% - 50% of the total daily dose is administered as basal insulin once daily.

• Prandial insulin:

  • The remaining portion is divided and administered before meals. Premeals insulins comprise mostly of rapid (Aspart, lispro, and glulisine) and short-acting (regular) insulins.

The dose of insulin Degludec should be adjusted at 3 - 7 days interval to minimize the risk of hypoglycemia.

Insulin Degludec Dose in the treatment of type 2 Diabetes mellitus:

• Basal insulin may be added to oral therapy if the patients' glycemic control is inadequate.
• Furthermore, if the glycated hemoglobin is greater than 10%, the blood glucose is more than 300 mg/dl and the patient is symptomatic, insulin may be considered as a part of initial treatment.
• Long-acting insulins may be preferred in patients at risk of hypoglycemia.

• Treatment initiation

  • Initiate with 8 - 10 units once a day or 0.1 - 0.2 units/kg once a day.
  • If the glycated hemoglobin is more than 8% before the initiation of basal insulin, treatment may be initiated at a higher dose (0.2 - 0.3 units/kg once a day).

Insulin Degludec Dosage adjustment:

• The dose may be adjusted by 10% - 15% or 2 - 4 units at weekly or twice weekly intervals until the target blood glucose levels are achieved.

• Patients who develop hypoglycemia:

  • Reduce the dose by 4 units or 10 - 20% of the usual dose.

• When prandial or pre meals insulin is added to the regimen:

  • The dose should be reduced by 4 units or 10% of the dose if the glycated hemoglobin is less than 8%.

• Patients receiving enteral feeding:

  • Advise 30 - 50% of the total daily dose as basal insulin and 50 - 70% of the TDD prior to feeding.

• Diabetic patients undergoing surgery:

  • Administer 60 - 80% of the usual dose of long-acting insulin in the morning or night before surgery.

• Conversion from other long-acting insulins:

  • Insulin Degludec should be initiated at the same dose of the previously administered long-acting insulin.

• If the dose is missed:

  • Administer the same dose as soon as possible. Ensure at least a gap of eight hours between 2 doses [Ref].

Insulin Degludec Dose in Children:

• Insulin dosing may vary with weight, age, duration of diabetes, caloric intake, physical activity, other concomitant medications, and the type of diabetes.
• It is aimed to achieve a euglycemic state. Insulin Degludec provides basal coverage.
• Most type 1 patients will still require short or rapid-acting insulin for prandial cover.
• Type 2 diabetes patients may require basal insulin along with oral anti-diabetic medications or basal and prandial insulin.
• Insulin Degludec is available in vials and FlexTouch pens as U-100 and U-200. FlexTouch pens U-200 can not deliver units that are odd in number.

Insulin Degludec dose in the treatment of Type 1 diabetes mellitus:

• General insulin dosing:

  • The usual maintenance total daily insulin dose ranges between 0.5 - 1 unit/kg/day in divided doses.
  • Treatment is initiated at a lower dose and adjusted according to the blood glucose levels.
  • Patients in partial remission or the honeymoon phase of diabetes may require less than 0.5 units/kg/day.
  • Prepubertal children not in remission may require 0.7 - 1 units/kg/day
  • During puberty and the adolescents period, the dose may substantially increase and the patients may require more than 1.2 units/kg/day.
  • The total daily dose is administered as 50 - 75% basal insulin and 25 - 50% prandial insulin.
  • Basal insulin may be any of the long-acting insulins like NPH, detemir, glargine, and Degludec. Prandial insulin may be regular insulin or the rapid-acting insulins (lispro, glulisine, and Aspart).
  • Basal insulin is usually given as once daily (except NPH that may be given twice) while the prandial insulin is administered as twice or thrice daily prior to meals.

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Insulin Degludec-specific dosing:

It should not be advised to children requiring 5 units or less.

Insulin-naive patients:

• The usual initial total daily dose is 0.2 - 0.4 units/kg/day out of which 1/3rd to 1/2 is administered as insulin Degludec and the rest is administered as short or rapid-actin insulin prior to each meal (prandial insulin).

Insulin-experienced patients:

• Patients already on long-acting insulin should be advised 80% of the insulin Degludec dose when switching from another long-acting insulin.

Dosage adjustment:

The dose should be adjusted every 3 - 4 days based on the patient's glucose levels and insulin requirement.

Insulin Degludec dose in children with Type 2 diabetes mellitus:

General insulin dosing:

Long-acting insulin may be added to metformin or other antidiabetic medicines as a once-daily subQ injection if the plasma glucose is more than 25 mg/dl or the glycated hemoglobin is 9% or more. Prandial insulin may be added if the target glucose is not reached despite the optimal dose.

Insulin Degludec-specific dosing:

• Insulin-naive patients:

  • 8 - 10 units once a day initially

• Insulin-experienced patients:

  • Patients should be advised insulin Degludec at 80% of the total daily dose of long or intermediate-acting insulin from which the patient is being converted

• Dosage adjustment:

  • The dose should be adjusted every 3 to 4 days based on the patient’s plasma glucose and the metabolic requirements.

Pregnancy Category C

• Data are limited regarding the use of insulin Degludec in pregnant patients.
• Insulin is preferred over other agents to treat hyperglycemia in pregnancy.
• Hyperglycemia in pregnancy is associated with significant fetal adverse effects including congenital malformations.
• For the best pregnancy outcomes, blood glucose should be kept as close to the target goals as possible without causing significant hypoglycemia.
• Insulin requirements usually fall during the first trimester and increase in the second and third trimesters peaking at 28 - 32 weeks of gestation.
• Insulin requirements fall rapidly following delivery.

Use during breastfeeding:

• Breastfeeding should be continued while the mother is on insulin.
• Experience with insulin Degludec during breastfeeding is limited.
• The manufacturer recommends using it with caution during breastfeeding.

Insulin Degludec dose in Kidney disease:

• Adjustment in the dose has not been provided by the manufacturer in patients with renal disease.
• Blood glucose should be frequently monitored and the dose adjusted accordingly.

Use in Liver disease:

• Adjustment in the dose has not been provided by the manufacturer in patients with liver disease.
• Blood glucose should be frequently monitored and the dose adjusted accordingly.

Insulin Degludec Side effects (Common):

• Central nervous system:

  • Headache

• Endocrine & metabolic:

  • Severe hypoglycemia

• Immunologic:

  • Antibody development

• Respiratory:

  • Nasopharyngitis
  • Upper respiratory tract infection

Less Common Side Effects of Insulin Tresiba Include:

• Cardiovascular:

  • Peripheral edema

• Gastrointestinal:

  • Diarrhea
  • Gastroenteritis

• Local:

  • Injection site reaction including
    • Discoloration
    • Erythema
    • Hematoma
    • Hemorrhage
    • Mass
    • Nodules
    • Pain
    • Pruritus

• Respiratory:

  • Sinusitis

Rare side effects on Insulin Tresiba:

• Endocrine & metabolic:

  • Hypokalemia
  • Weight gain

Insulin Degludec Contraindications:

• Allergic reactions to insulin Degludec or any component of the formulation
• Hypoglycemic episodes.

Insulin Degludec Warnings & Precautions

• Glycemic control:

  • Changes in the insulin formulations and strengths may result in a change in blood glucose levels.
  • The most common side effect of insulins and insulin Degludec is hypoglycemia.
  • Patients who skip their meals, perform strenuous exercise, have renal or hepatic dysfunction are especially at risk of developing hypoglycemia.
  • Recovery from hypoglycemia may be delayed in patients on long-acting preparations of insulins like glargine, detemir, and insulin Degludec.
  • The symptoms of hypoglycemia may be masked in patients who experience recurrent hypoglycemia, those on Beta-Blockers, patients with long-standing diabetes, and patients with diabetic neuropathy.
  • Severe hypoglycemia may result in seizures, coma, brain damage, and even death.

• Hypersensitivity:

  • Treatment must be discontinued if the patient develops allergic reactions.
  • Allergic reactions including anaphylaxis may be severe and life-threatening.

• Hypokalemia:

  • Hypokalemia may occur in patients on insulin as a result of the intracellular shift of potassium. Hypokalemia may result in serious cardiac arrhythmias.
  • Potassium supplementation may be required.

• Diabetic ketoacidosis:

  • Patients with diabetic ketoacidosis should be advised rapid or short-acting insulin.
  • It should be avoided in such patients.

• Hepatic impairment:

  • Patients with hepatic impairment should be advised insulin Degludec with caution and may require dose adjustment.

• Renal impairment:

  • Patients with renal impairment may require dose adjustment. It should be used with caution in patients with renal impairment.

Insulin degludec: Drug Interaction

Monitoring Parameters:

• Monitor the patient’s blood sugars, glycated hemoglobin, and weight at regular intervals.
• Prior to initiating therapy, renal and liver functions should be monitored.
• The target premeals blood sugars should be kept between 70 – 130 mg/dl, Post-prandial blood sugars should be kept to less than 180 mg/dl, while the glycated hemoglobin to less than 7% (for most patients, although, it should be individualized).

How to administer Insulin degludec?

• It is administered subQ into the thigh, upper arm, or abdomen using the U-100 insulin syringes.

Intramuscular, Intravenous, or administration via an insulin infusion pump should be avoided.

• The rate of absorption varies depending on the site of injection.
• The site of injection should be rotated to reduce the risk of lipodystrophy. It is administered as a once-daily injection at any time of the day.

Administration using FlexTouch pens:

• Switching from a vial to flexpen does not need any dose conversion.
• The number of units to be delivered is shown in the dose window for both U-100 and U-200.
• However, U-200 can not be used to inject an odd number of units.
• It should not be mixed with other insulin formulations or solutions.

Mechanism of action of Insulin Degludec:

• Insulin regulates the metabolism of carbohydrates, fats, and proteins.
• It stimulates glycogen synthesis and fatty acids in the liver.
• In the skeletal muscles, it results in protein synthesis and increased glycogen synthesis.
• In adipose tissues, it stimulates triglyceride synthesis, process lipoproteins to provide free fatty acids.
• It also stimulates the cellular uptake of proteins and promotes potassium uptake by the cells by activating the sodium-potassium ATPases.
• Insulin Degludec is a long-acting insulin analog that has slightly different amino acid sequences in its structure.
• It lacks the amino acid threonine in position B-30 of the B-chain and has a side chain composed of glutamic acid and a C16 fatty acid.
• The various insulin formulations are categorized based on their onset of action, peak, and duration of effect as rapid, short, intermediate, and long-acting insulin.
• The onset and duration of action also depend on the site of administration, local blood supply, temperature, lipodystrophy, and exercise.

Insulin Degludec is a long-acting insulin analog.

The onset of action of insulin degludec is about one hour. 99% of it is bound to proteins and it has a half-life elimination of about 25 hours that is independent of the dose with a peak onset of action in about 9 hours. 

Insulin degludec Brand Names (International):

• Tregludec
• Tresiba

Insulin Degludec Brand Names in Pakistan:

No brands of Insulin Degludec available in Pakistan. It is, however, available in combination with insulin Aspart by the brand name of Insulin Ryzodeg