Introduction
Tresiba (insulin degludec) is a long-acting basal insulin analog approved by the FDA in 2015 for the treatment of diabetes mellitus. It provides stable, ultra-long duration basal insulin coverage with a flat and stable pharmacokinetic profile. Tresiba represents an important advancement in insulin therapy due to its prolonged duration of action (up to 42 hours) and reduced risk of hypoglycemia compared to other basal insulins.
Mechanism of Action
Insulin degludec works by binding to insulin receptors on target cells (primarily muscle, fat, and liver cells), facilitating cellular glucose uptake, inhibiting hepatic glucose production, and promoting protein synthesis and lipid metabolism. Its unique mechanism involves the formation of soluble multi-hexamers at the injection site, which slowly dissociate into monomers that are absorbed into the bloodstream, resulting in a stable and prolonged action profile.
Indications
- Treatment of type 1 diabetes mellitus in adults and pediatric patients ≥1 year of age
- Treatment of type 2 diabetes mellitus in adults
- May be used in combination with other antihyperglycemic agents
Dosage and Administration
Initial dosing:- Type 1 diabetes: Typically ⅓ to ½ of total daily insulin dose as basal insulin
- Type 2 diabetes: 10 units daily or 0.1-0.2 units/kg/day
- Subcutaneous injection once daily at any time of day
- Can be administered with or without meals
- Rotate injection sites (abdomen, thigh, or upper arm)
- If missed, administer as soon as remembered, then resume regular schedule
- Renal impairment: No dosage adjustment required
- Hepatic impairment: Requires careful titration and monitoring
- Elderly: May require lower initial doses
Pharmacokinetics
Absorption: Slow, consistent absorption with onset of action within 1-2 hours Distribution: Binds to plasma proteins and insulin receptors Metabolism: Undergoes hepatic metabolism via insulin-degrading enzyme and insulin receptors Elimination: Half-life approximately 25 hours; duration of action up to 42 hours Steady-state: Achieved after 2-3 days of administrationContraindications
- Hypersensitivity to insulin degludec or any component of the formulation
- During episodes of hypoglycemia
- Not for intravenous or intramuscular administration
- Not for use in insulin infusion pumps
Warnings and Precautions
- Hypoglycemia: Most common adverse reaction; risk increased with renal/hepatic impairment, alcohol use, and concomitant glucose-lowering medications
- Hypokalemia: Insulin preparations may cause potassium shifts into cells
- Fluid retention: Can occur with initiation or dose increases
- Lipodystrophy: May occur at injection sites
- Weight gain: Common with insulin therapy
- Allergic reactions: Both local and systemic reactions possible
Drug Interactions
Drugs that may increase hypoglycemia risk:- Other antidiabetic agents (especially sulfonylureas, meglitinides)
- ACE inhibitors
- Beta-blockers (may mask hypoglycemia symptoms)
- Disopyramide
- Fluoxetine
- Monoamine oxidase inhibitors
- Pentoxifylline
- Propoxyphene
- Salicylates
- Somatostatin analogs
- GLP-1 receptor agonists
- Corticosteroids
- Diuretics
- Sympathomimetic agents
- Phenothiazines
- Thyroid hormones
- Estrogens
- Protease inhibitors
- Atypical antipsychotics
Adverse Effects
Very common (>10%):- Hypoglycemia
- Injection site reactions
- Weight gain
- Allergic reactions
- Peripheral edema
- Lipodystrophy
- Pruritus
- Rash
Monitoring Parameters
- Blood glucose levels (fasting and postprandial)
- HbA1c every 3 months until stable, then every 6 months
- Hypoglycemia symptoms and frequency
- Injection sites for lipodystrophy or reactions
- Renal and hepatic function
- Electrolytes (particularly potassium)
- Weight changes
- Signs of fluid retention
Patient Education
- Proper injection technique and site rotation
- Recognition and management of hypoglycemia symptoms
- Importance of consistent meal timing and carbohydrate intake
- Never share insulin pens or needles
- Storage requirements (refrigerate unopened pens; room temperature for in-use pens for up to 56 days)
- Travel considerations (time zone changes may require dose adjustment)
- Carry glucose source at all times
- Inform healthcare providers about all medications
- Regular self-monitoring of blood glucose
- When to seek medical attention (severe hypoglycemia, allergic reactions)
References
1. FDA Prescribing Information: Tresiba (insulin degludec) injection. 2022. 2. Garber AJ, et al. Lancet. 2012;379(9825):1489-1497. 3. Heller S, et al. Diabetes Care. 2012;35(12):2464-2471. 4. Ratner RE, et al. Diabetes Obes Metab. 2013;15(2):175-184. 5. Mathieu C, et al. Lancet Diabetes Endocrinol. 2018;6(8):605-617. 6. American Diabetes Association. Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S1-S291. 7. Davies MJ, et al. Diabetes Care. 2022;45(11):2753-2786.