Dosing and uses of Tresiba (insulin degludec)
Adult dosage forms and strengths
prefilled pen
- 100 units/mL
- 200 units/mL
Diabetes Mellitus Types 1 & 2
Long-acting basal insulin indicated to improve glycemic control in adults with diabetes mellitus
Starting dose in insulin naïve patients
- Type 1 diabetes mellitus: ~One third to one half of the total daily insulin dose; as a general rule, 0.2-0.4 units/kg can be used to calculate the initial total daily insulin dose in insulin-naïve patients with type 1 diabetes
- Type 2 diabetes mellitus: 10 units SC once daily
Starting dose in patients already on insulin therapy
- Type 1 and type 2 diabetes mellitus: Start insulin degludec at the same unit dose as the total daily long- or intermediate-acting insulin unit dose
Dosing Considerations
Not indicated for diabetic ketoacidosis
Pediatric dosage forms and strengths
Safety and efficacy not established
Tresiba (insulin degludec) adverse (side) effects
>10%
Nasopharyngitis (12.9-23.9%)
Severe hypoglycemic episode (0.3-12.3%)
Upper respiratory tract infection (8.4-11.9%)
Headache (8.8-11.8%)
1-10%
Diarrhea (6.3%)
Sinusitis (5.1%)
Gastroenteritis (5.1%)
Injection site reactions (3.8%)
Peripheral edema (0.9-3%)
<1%
Lipodystrophy
Warnings
Contraindications
During episodes of hypoglycemia
Documented hypersensitivity
Cautions
Do not share, even if the needle is changed; sharing poses a risk for transmission of blood-borne pathogens
Changes in insulin, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia; these changes should be made cautiously and only under medical supervision, and the frequency of blood glucose monitoring should be increased
Severe, life-threatening, generalized allergy, including anaphylaxis, can occur
All insulin products cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia; monitor potassium levels in patients at risk for hypokalemia including patients using potassium-lowering medications or those taking medications sensitive to serum potassium concentrations; treat if indicated
Thiazolidinediones, which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists can cause dose-related fluid retention, particularly when used in combination with insulin; this may lead to or exacerbate heart failure
Hypoglycemia
- Hypoglycemia is the most common adverse effect and can happen suddenly; severe hypoglycemia can cause seizures, may be life-threatening, or cause death
- Hypoglycemia can impair concentration ability and reaction time and place an individual and others at risk in situations where these abilities are important (eg, driving or operating other machinery)
- Risk increases with intensity of glycemic control and is related to the duration of action of the insulin
- Other factors that may increase the risk of hypoglycemia include changes in meal pattern (eg, macronutrient content or timing of meals), changes in level of physical activity, or changes to coadministered medication
- Renal or hepatic impairment may increase hypoglycemia risk
- In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended
- Accidental mix-ups between basal insulin products and other insulins, particularly rapid-insulins, have been reported
- Do not transfer insulin degludec from the prefilled pen to a syringe; the markings on the insulin syringe will not measure the dose correctly and can result in overdosage and severe hypoglycemia
Pregnancy
Pregnancy
Pregnancy category: C
Animal studies
- The effect of insulin degludec was consistent with those observed with human insulin as both caused preimplantation and postimplantation losses and visceral/skeletal abnormalities in rats at an insulin degludec dose of 21 U/kg/day (~5 times the human exposure [AUC] at a human SC dose of 0.75 U/kg/day) and in rabbits at a dose of 3.3 U/kg/day (~10 times the AUC at a human SC dose of 0.75 U/kg/day)
- The effects are probably secondary to maternal hypoglycemia
Lactation
Unknown if distributed in human breast milk
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Tresiba (insulin degludec)
Mechanism of action
Once-daily basal insulin analogue
Insulin and its analogues lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production; insulin inhibits lipolysis and proteolysis and enhances protein synthesis; targets include skeletal muscle, liver, and adipose tissue
Absorption
Peak plasma time: 9 hr
Peak plasma concentration: 4472 pmol/L
Steady state: 3-4 days
Distribution
Protein bound: >99% to albumin
Metabolism
Metabolites: Inactive
Elimination
Half-life: ~25 hr
Clearance: 0.03 L/kg
Administration
Preparation
Inspect visually for particulate matter and discoloration; only use if the solution appears clear and colorless
Do not dilute or mix with any other insulin products or solutions
Do not transfer drug from the insulin degludec pen into a syringe for administration
SC Administration
Inject SC once daily at any time of day
Inject SC into the thigh, upper arm, or abdomen
Rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy
Do not administer IV, IM, or in an insulin infusion pump
Individualize and titrate the dose based on the patient’s metabolic needs, blood glucose monitoring results, and glycemic control goaL
The recommended days between dose increases is 3-4 days
Dose adjustments may be needed with changes in physical activity, changes in meal patterns (ie, macronutrient content or timing of food intake), changes in renal or hepatic function, or during acute illness to minimize the risk of hypoglycemia or hyperglycemia
Instruct patients who miss a dose to inject their daily dose during waking hours upon discovering the missed dose
Instruct patients to ensure that at least 8 hr have elapsed between consecutive insulin degludec injections
DO NOT perform dose conversion when using the insulin degludec U-100 or U-200 FlexTouch pens; the dose window for both the U-100 and U-200 FlexTouch pens shows the number of insulin units to be delivered and NO conversion is needed
Storage
Unopened (not in-use) prefilled pen
- Refrigerate at 36-46°F (2-8°C)
- Do not store in the freezer or directly adjacent to the refrigerator cooling element
- Do not freeze
- Do not use if it has been frozen
Open (in-use) prefilled pen
- Should NOT be refrigerated but should be kept at room temperature (<86°F [30°C])
- Keep away from direct heat and light
- The opened pen may be used for up to 56 days (8 wk) after being opened, if it is kept at room temperature
