Version May 2024
Dosage guidance:
Clinical considerations: Insulin degludec is a basal insulin. Insulin requirements vary between patients; monitor glucose levels frequently and individualize dose.
Diabetes mellitus, type 1, treatment:
Note: Insulin degludec must be used concomitantly with rapid- or short-acting insulins (ie, multiple daily injections regimen). The total daily doses (TDDs) presented below are expressed as the total units/kg/day of all insulin formulations (basal and prandial) combined.
General insulin dosing :
Initial TDD: SUBQ: 0.4 to 0.5 units/kg/day; conservative initial doses of 0.2 to 0.4 units/kg/day may be considered to avoid hypoglycemia (Ref).
Usual TDD maintenance range: SUBQ: 0.4 to 1 units/kg/day in divided doses (Ref).
Division of TDD (multiple daily injections):
Basal insulin: SUBQ: 40% to 50% of the TDD administered as insulin degludec once daily (Ref).
Prandial insulin: SUBQ: The remaining portion (ie, 50% to 60%) of the TDD is divided and administered before, at, or just after mealtimes, depending on the formulation (Ref).
Dosage adjustment for glycemic control: SUBQ: Increase or decrease daily dose by 10% to 20% once or twice weekly (eg, every 3 or 7 days) to maintain premeal and bedtime glucose in target range; avoid more frequent dosage adjustment to minimize hypoglycemia risk (Ref).
Preoperative dosage adjustment:
Once-daily evening administration: SUBQ: Reduce insulin degludec dose by 10% to 25% the evening before the procedure; may administer the full dose in patients whose glucose levels are generally elevated (eg, >200 mg/dL) (Ref).
Once-daily morning administration: SUBQ: Administer one-half to two-thirds of the total morning insulin dose (basal + prandial) as insulin degludec the morning of the procedure (Ref).
Diabetes mellitus, type 2, treatment:
Note: Preferred in patients with symptomatic hyperglycemia (eg, weight loss, polydipsia, polyuria) or ketonuria; may also be used in patients with severe hyperglycemia (eg, fasting glucose >250 mg/dL, random glucose consistently >300 mg/dL, HbA1c >9%), or if glycemic goals are not met despite adequately titrated metformin with or without other noninsulin agents (Ref). Consider discontinuation or a dose reduction of sulfonylureas and thiazolidinediones when initiating basal insulin therapy (Ref).
Initial: SUBQ: 10 units once daily or 0.1 to 0.2 units/kg once daily (Ref). In patients with HbA1c >8%, fasting plasma glucose >250 mg/dL, or insulin resistance, 0.2 to 0.3 units/kg/day is recommended (Ref). Some experts use a minimum of 10 units/day and do not exceed 20 units/day for the initial dose (Ref).
Dosage adjustment:
For persistently elevated fasting plasma glucose: SUBQ: Increase daily dose by 2 to 4 units or by 10% to 20% every 3 to 7 days to achieve fasting plasma glucose target while avoiding hypoglycemia (Ref).
For elevated HbA1c despite achieving fasting plasma glucose target: SUBQ: Encourage lifestyle modifications. Consider adding other medications (eg, a glucagon-like peptide-1 receptor agonist or prandial insulin before the largest meal). In some patients, higher insulin degludec doses (eg, >0.5 units/kg/day) may provide diminishing additional improvements in HbA1c (Ref).
For hypoglycemia: SUBQ: For unexplained mild to moderate hypoglycemia, consider decreasing daily dose by 10% to 20% (Ref); for severe hypoglycemia requiring assistance from another person or blood glucose <40 mg/dL, consider decreasing daily dose by 20% to 50% (Ref).
Dosage adjustment when adding prandial insulin: SUBQ: In patients whose glucose levels are close to target (eg, HbA1c <8%), consider decreasing the basal insulin daily dose by 4 units or by 10% (Ref).
Preoperative dosage adjustment:
Evening dosage adjustment: SUBQ: Reduce insulin degludec dose by 10% to 25% the evening before the procedure; may administer the full dose if preoperative hypoglycemia risk is low (eg, glucose levels generally >200 mg/dL) (Ref).
Morning dosage adjustment: SUBQ: For patients not using prandial insulin, reduce insulin degludec dose by 10% to 25% the morning of the procedure; may administer the full dose if preoperative hypoglycemia risk is low (eg, glucose levels generally >200 mg/dL). For patients using prandial insulin, omit prandial insulin after fasting begins and administer one-half to two-thirds of the total morning insulin dose (basal + prandial) as insulin degludec the morning of the procedure (Ref).
Conversion from other basal insulins to insulin degludec: SUBQ: Initial: May be substituted on an equivalent unit-per-unit basis; in patients taking twice-daily basal insulin (eg, with insulin NPH or detemir), may consider a 10% to 20% dose reduction when converting to once-daily insulin degludec if hypoglycemia is a concern (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.
There are no dosage adjustments provided in the manufacturer's labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.
Refer to adult dosing.
(For additional information see "Insulin degludec: Pediatric drug information")
Dosage guidance:
Dosing: U-200 FlexTouch pens do not allow odd numbered dosing of insulin units; patients requiring odd numbered doses should use the U-100 FlexTouch pen. Doses <5 units of insulin degludec should be administered from the U-100 vial and not the pens.
Clinical considerations: Insulin degludec is a long-acting insulin. Insulin doses should be individualized based on patient needs; adjustments may be necessary with changes in physical activity, meal patterns, acute illness, or with changes in renal or hepatic function. Insulin requirements vary dramatically between patients and dictate frequent monitoring and close medical supervision. Insulin regimens vary widely by region, practice, and institution; consult institution-specific guidelines.
Diabetes mellitus, type 1: Children and Adolescents: Note: For basal insulin coverage, long-acting insulin analogs are preferred over insulin NPH due to decreased risk of hypoglycemia (Ref). Insulin degludec must be used in combination with a rapid or short-acting insulin.
Insulin degludec-specific dosing: Note: All pediatric patients should have rapid-acting or regular insulin available for prevention and management of hyperglycemia and ketosis emergencies (Ref).
Children and Adolescents: SUBQ: Initial: Approximately one-third to one-half of the total daily insulin requirement administered once daily; a rapid-acting or short-acting insulin should also be used to complete the balance of the total daily insulin requirement (a general rule for initial total daily insulin dose in patients who are insulin naive: 0.2 to 0.4 units/kg/day). Adjust dosage every 3 to 4 days as needed based on patient's metabolic needs, blood glucose monitoring results, and glycemic control goal.
General insulin dosing: The daily doses presented below are expressed as the total units/kg/day of all insulin formulations (basal and prandial) combined.
Initial total daily insulin: SUBQ: Initial: 0.4 to 0.5 units/kg/day in divided doses (Ref); usual range: 0.4 to 1 units/kg/day in divided doses (Ref); lower doses (0.25 units/kg/day) may be used, especially in young children to avoid potential hypoglycemia (Ref); higher doses may be necessary for some patients (eg, concomitant steroids, puberty, sedentary lifestyle, obesity, following diabetic ketoacidosis presentation) (Ref).
Usual total daily maintenance range: SUBQ: Doses must be individualized; however, an estimate can be determined based on phase of diabetes and level of maturity (Ref).
Partial remission phase ("honeymoon" phase): <0.5 units/kg/day.
Prepubertal children (not in partial remission):
Children ≤6 years: 0.4 to 0.8 units/kg/day.
Children ≥7 years: 0.7 to 1 units/kg/day.
Pubescent Children and Adolescents: During puberty, requirements may substantially increase to >1 unit/kg/day and in some cases up to 2 units/kg/day.
Division of daily insulin requirement (multiple daily injections):
Basal insulin: Generally, ~30% to 50% of the total daily insulin is given as basal insulin (intermediate- or long-acting) in 1 to 2 daily injections (Ref).
Prandial insulin: The remaining portion of the total daily dose is then divided and administered before or at mealtimes (depending on the formulation) as a rapid-acting (eg, aspart, glulisine, lispro) or short-acting (regular) insulin. In most patients with type 1 diabetes, the use of a rapid-acting insulin analog is preferred over regular insulin to reduce hypoglycemia risk (Ref).
Dosage adjustment for glycemic control: Treatment and monitoring regimens must be individualized to maintain premeal and bedtime glucose in target range; titrate dose to achieve glucose control and avoid hypoglycemia. Since combinations of agents are frequently used, dosage adjustment must address the individual component of the insulin regimen that most directly influences the blood glucose value in question, based on the known onset and duration of the insulin component. Titrate insulin degludec dose every 3 to 4 days based on patient's metabolic needs, blood glucose monitoring results, and glycemic control goal.
Surgical patients (Ref): Note: Patients with diabetes should be scheduled as the first case of the day.
Minor surgeries (surgery lasting <2 hours, with or without sedation or anesthesia, where rapid recovery is anticipated and patient is expected to be able to eat within 2 to 4 hours).
Morning or afternoon procedure: Administer the usual insulin degludec dose (if usually given in the morning); may consider reducing dose to 70% to 80% of usual dose if preoperative evaluation shows low morning blood glucose values. Alternatively, may administer IV insulin (regular) infusion; begin IV fluids containing dextrose; in general, rapid-acting insulin should be omitted until after surgery and patient is able to eat unless it is needed to correct significant hyperglycemia and/or significant ketone (>0.6 mmol/L) production is present.
Postprocedure: Once normal oral intake is achieved, resume usual insulin regimen; monitor closely; insulin requirement may vary due to changes related to surgery (ie, oral intake, nausea, postoperative stress, pain, inactivity).
Major surgeries (any surgery under anesthesia that is more than minor, typically lasting >2 hours with a high likelihood of postoperative nausea, vomiting, and/or inability to adequately feed after procedure):
Evening prior to surgery: If patient normally receives evening insulin doses, administer the usual evening and/or bedtime insulin degludec dose; some experts recommend reducing bedtime basal insulin dose to 70% to 80% of usual dose.
Morning of surgery: Omit morning insulin (short- and long-acting) and start IV insulin (regular) infusion and IV fluids containing dextrose.
Postprocedure: Once normal oral intake is achieved, resume usual insulin regimen; monitor closely; insulin requirement may vary due to changes related to surgery (ie, postoperative stress, medication changes, inactivity).
Diabetes mellitus, type 2: The goal of therapy is to achieve an HbA1c <7% as quickly as possible using the safe titration of medications (Ref).
Insulin degludec-specific dosing:
Children and Adolescents (patients who are insulin naive): SUBQ: Initial: 10 units once daily; titrate dose every 3 to 4 days as needed based on patient's metabolic needs, blood glucose monitoring results, and glycemic control goal.
General insulin dosing:
Newly diagnosed patients : Note: Recommended for use in metabolically unstable patients (eg, plasma glucose ≥250 mg/dL, HbA1c ≥8.5%, and symptoms excluding acidosis) while metformin is initiated and titrated; may also be used for patients with ketosis/ketoacidosis/ketonuria to correct the hyperglycemia and the metabolic derangement (Ref).
Children ≥10 years and Adolescents:
Initial therapy: SUBQ: 0.25 to 0.5 units/kg/dose once daily; titrate every 3 to 4 days as needed based on plasma glucose; use in combination with lifestyle changes and metformin to achieve goals (Ref).
Subsequent therapy: SUBQ:
Glycemic goal achieved: Once initial goal reached, insulin should be slowly tapered over 2 to 6 weeks by decreasing the insulin dose by 30% to 50% each time the metformin dose is increased and the patient transitioned to metformin monotherapy if able (Ref).
Failure to achieve glycemic goal: In patients in whom glycemic goals are not achieved with insulin degludec (up to 1.5 units/kg/day) and maximum metformin dose, consider initiating prandial insulin (regular insulin or rapid-acting insulin) (Ref). Note: Insulin resistance is common with type 2 diabetes and doses >1.5 units/kg/day may be necessary to achieve glycemic control, especially in patients with high A1c and patients in mid to late puberty; may consider use of more concentrated insulin degludec preparations (200 units/mL) to avoid large volume injections that may affect medication adherence (Ref).
Patients on established therapy: Note: Recommended for use when glycemic goals can no longer be met using metformin alone, or if contraindications or intolerable side effects of metformin develop (Ref).
Children ≥10 years and Adolescents: SUBQ: Initial: 0.25 to 0.5 units/kg/dose once daily; may be used alone or in combination with metformin (if not contraindicated); may be titrated as needed based on plasma glucose. If glycemic goals are not achieved at 1.5 units/kg/day, evaluate adherence; if adherence confirmed, initiate prandial insulin (regular insulin or rapid-acting insulin) (Ref). Note: Insulin resistance is common with type 2 diabetes and doses >1.5 units/kg/day may be necessary to achieve glycemic control, especially in patients with high A1c and patients in mid to late puberty; may consider use of more concentrated insulin degludec preparations (200 units/mL) to avoid large volume injections that may affect medication adherence (Ref).
Conversion from other basal insulins to insulin degludec: Children and Adolescents: SUBQ: Initial: Initiate insulin degludec at 80% of the total daily long- or intermediate-acting insulin dose from which the patient is being converted to minimize risk of hypoglycemia.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.
There are no dosage adjustments provided in the manufacturer's labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Endocrine & metabolic: Severe hypoglycemia (type 1 diabetics on combination insulin therapy: 10% to 18%; type 2 diabetics on combination therapy: ≤5%)
Immunologic: Antibody development
Nervous system: Headache (9% to 12%)
Respiratory: Nasopharyngitis (13% to 24%), upper respiratory tract infection (8% to 12%)
1% to 10%:
Cardiovascular: Peripheral edema (type 2 diabetes: 3%; type 1 diabetes: <1%)
Gastrointestinal: Diarrhea (type 2 diabetes: 6%), gastroenteritis (type 1 diabetes: 5%)
Local: Injection site reaction (4%)
Respiratory: Sinusitis (type 1 diabetes: 5%)
<1%:
Dermatologic: Urticaria
Hypersensitivity: Hypersensitivity reaction
Local: Hypertrophy at injection site (lipohypertrophy), lipoatrophy at injection site, lipotrophy at injection site (lipodystrophy)
Frequency not defined: Endocrine & metabolic: Hypokalemia, weight gain
Postmarketing: Endocrine & metabolic: Amyloidosis (localized cutaneous at injection site)
Hypersensitivity to insulin degludec or any component of the formulation; during episodes of hypoglycemia
Concerns related to adverse effects:
• Glycemic control: Hyper- or hypoglycemia may result from changes in insulin strength, manufacturer, type, and/or administration method. The most common adverse effect of insulin is hypoglycemia. The timing of hypoglycemia differs among various insulin formulations. Hypoglycemia may result from changes in meal pattern (eg, macronutrient content, timing of meals), changes in the level of physical activity, increased work or exercise without eating, or changes to coadministered medications. Use of long-acting insulin preparations (eg, insulin degludec, insulin detemir, insulin glargine) may delay recovery from hypoglycemia. Patients with renal or hepatic impairment may be at a higher risk. Symptoms differ in patients and may change over time in the same patient; awareness may be less pronounced in those with long-standing diabetes, diabetic nerve disease, patients taking beta-blockers, or in those who experience recurrent hypoglycemia. Profound and prolonged episodes of hypoglycemia may result in convulsions, unconsciousness, temporary or permanent brain damage, or even death. Insulin requirements may be altered during illness, emotional disturbances, or other stressors. Instruct patients to use caution with ethanol; may increase risk of hypoglycemia.
• Hypersensitivity: Severe, life-threatening allergic reactions, including anaphylaxis, may occur. If hypersensitivity reactions occur, discontinue therapy.
• Hypokalemia: Insulin (especially IV insulin) causes a shift of potassium from the extracellular space to the intracellular space, possibly producing hypokalemia. If left untreated, hypokalemia may result in respiratory paralysis, ventricular arrhythmia and even death. Use with caution in patients at risk for hypokalemia (eg, loop diuretic use). Monitor serum potassium and supplement potassium when necessary.
Disease-related concerns:
• Bariatric surgery:
– Type 2 diabetes, hypoglycemia: Closely monitor insulin dose requirement throughout active weight loss with a goal of eliminating antidiabetic therapy or transitioning to agents without hypoglycemic potential; hypoglycemia after gastric bypass, sleeve gastrectomy, and gastric band may occur (Mechanick 2019). Insulin secretion and sensitivity may be partially or completely restored early after these procedures (gastric bypass is most effective, followed by sleeve and finally band) (Korner 2009; Peterli 2012). Monitoring of hospital insulin requirements is recommended to guide discharge insulin dose. Rates and timing of type 2 diabetes improvement and resolution vary widely by patient; insulin dose reduction of 75% has been suggested after gastric bypass for patients without severe β-cell failure (fasting c-peptide <0.3 nmol/L) (Cruijsen 2014).
– Weight gain: Insulin therapy is preferred if antidiabetic therapy is required during the perioperative period (Mechanick 2019). Evaluate risk versus benefit of long-term postoperative use and consider alternative therapy due to potential for insulin-induced weight gain (Apovian 2015).
• Cardiac disease: Concurrent use with peroxisome proliferator-activated receptor (PPAR)-gamma agonists, including thiazolidinediones (TZDs) may cause dose-related fluid retention and lead to or exacerbate heart failure, particularly when used in combination with insulin. If PPAR-gamma agonists are prescribed, monitor for signs and symptoms of heart failure. If heart failure develops, consider PPAR-gamma agonist dosage reduction or therapy discontinuation.
• Diabetic ketoacidosis: Should not be used in patients with diabetic ketoacidosis; use of a rapid-acting or short-acting insulin is required.
• Hepatic impairment: Use with caution in patients with hepatic impairment. Dosage requirements may be reduced.
• Renal impairment: Use with caution in patients with renal impairment. Dosage requirements may be reduced.
Special populations:
• Hospitalized patients: Prolonged use of a sliding scale insulin regimen in the inpatient setting is strongly discouraged. In the critical care setting, continuous IV insulin infusion (insulin regular) has been shown to best achieve glycemic targets. In noncritically ill patients with either poor oral intake or taking nothing by mouth, basal insulin use is preferred, with correctional doses (insulin regular or rapid-acting insulin) as needed. In noncritically ill patients with adequate nutritional intake, a combination of basal insulin along with nutritional and correctional components (insulin regular or rapid-acting insulin) is preferred. An effective insulin regimen will achieve the goal glucose range without the risk of severe hypoglycemia. A blood glucose value <70 mg/dL should prompt a treatment regimen review and change, if necessary, to prevent further hypoglycemia (ADA 2023).
• Obesity: A decrease in glucose lowering effect of insulin degludec with increasing BMI has been observed.
Dosage form specific issues:
• Multiple dose injection pens: According to the Centers for Disease Control and Prevention (CDC), pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).
Other warnings/precautions:
• Administration: Insulin degludec is a clear solution, but it is NOT intended for IV or IM administration or via an insulin pump.
• Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous:
Tresiba: 100 units/mL (10 mL) [contains metacresol, phenol]
Generic: 100 units/mL (10 mL)
Solution Pen-injector, Subcutaneous:
Tresiba FlexTouch: 100 units/mL (3 mL); 200 units/mL (3 mL) [contains metacresol, phenol]
Generic: 100 units/mL (3 mL); 200 units/mL (3 mL)
Yes
Solution (Insulin Degludec Subcutaneous)
100 units/mL (per mL): $14.24
Solution (Tresiba Subcutaneous)
100 units/mL (per mL): $40.67
Solution Pen-injector (Tresiba FlexTouch Subcutaneous)
100 units/mL (per mL): $40.67
200 units/mL (per mL): $81.35
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Cartridge, Subcutaneous:
Tresiba Penfill: 100 units/mL (3 mL) [contains metacresol, phenol]
Solution Pen-injector, Subcutaneous:
Tresiba: 100 units/mL (3 mL); 200 units/mL (3 mL) [contains metacresol, phenol]
Subcutaneous: For subcutaneous administration into the thigh, upper arm, or abdomen; do not administer IM or IV, or in an insulin infusion pump. Absorption rates vary amongst injection sites; be consistent with area used while rotating injection sites within the same region to reduce the risk of lipodystrophy or localized cutaneous amyloidosis. Rotating from an injection site where lipodystrophy/cutaneous amyloidosis is present to an unaffected site may increase risk of hypoglycemia. Insulin degludec should be administered once daily at any time of the day. Multidose vials should be used in patients requiring <5 units per day.
FlexTouch pens: Do not perform dose conversion when using the FlexTouch pen. The dose window for both U-100 and U-200 FlexTouch pens show the number of insulin units to be delivered and no conversion is needed. U-200 FlexTouch pens do not allow odd numbered dosing of insulin units; patients requiring odd numbered doses should use the U-100 FlexTouch pen. Do not dilute or mix insulin degludec with any other insulin formulation or solution; do not transfer from the FlexTouch pen into a syringe for administration. For both U-100 and U-200 FlexTouch pens, prime the needle before each injection with 2 units of insulin (use a new needle for each injection). Once injected, continue to depress the button until the dial has returned to 0 and for an additional 6 seconds. Then, remove the needle.
Vials: Administer using U-100 insulin syringes.
Parenteral: SUBQ: Do not use if solution is viscous or cloudy; use only if clear and colorless with no visible particulates. Do not dilute or mix insulin degludec with any other insulin formulation or solution. For subcutaneous administration into the thigh, upper arm, or abdomen; do not administer IM or IV, or in an insulin infusion pump. Administer once daily, at any time of day, but at the same time each day in pediatric patients. Absorption rates vary amongst injection sites; be consistent with area used while rotating injection sites within the same region to reduce the risk of lipodystrophy or localized cutaneous amyloidosis. Rotating from an injection site where lipodystrophy/cutaneous amyloidosis is present to an unaffected site may increase risk of hypoglycemia.
Vials (100 units/mL): Administer using U-100 insulin syringes. Multidose vials must be used in patients requiring <5 units per day.
FlexTouch pens: FlexTouch pens are available in concentrations of 100 units/mL and 200 units/mL. Do not transfer from the FlexTouch pen into a syringe for administration. Devices are designed to display the actual insulin units administered; do not perform dose conversion when using the FlexTouch pen. The dose window shows the number of insulin units to be delivered and no conversion is needed. For both U-100 and U-200 FlexTouch pens, prime the needle before each injection with 2 units of insulin (use a new needle for each injection); see manufacturer's labeling for specific procedure. Once primed, set dial to the appropriate dose, insert needle into clean skin, and activate device by holding the button down; continue to hold the button until the dose dial has returned to 0 units. After the insulin is injected, hold the needle in the skin for 6 seconds after the dose dial has returned to 0 units before removing the needle to ensure the full dose has been administered. Do not rub the area.
U-100 FlexTouch pen: Device delivers doses in 1-unit increments and can deliver up to 80 units in a single injection.
U-200 FlexTouch pens: Device delivers doses in 2-unit increments and can deliver up to 160 units in a single injection. Do not use for patients requiring odd numbered doses; U-100 FlexTouch pen must be used for patients requiring odd numbered doses.
Diabetes mellitus, types 1 and 2, treatment: To improve glycemic control in patients ≥1 year of age with type 1 or type 2 diabetes mellitus.
Tresiba may be confused with Tanzeum [DSC], Tarceva, Toujeo, Tradjenta, Trulicity
The Institute for Safe Medication Practices (ISMP) includes insulins among its classes of drugs which have a heightened risk of causing significant patient harm when used in error. Due to the number of insulin preparations, it is essential to identify/clarify the type of insulin to be used.
Insulin degludec is a clear solution, but it is NOT intended for IV or IM administration.
U-200 FlexTouch pens do not allow odd numbered dosing of insulin units; patients requiring odd numbered doses should be prescribed the U-100 FlexTouch pen or U-100 multidose vials.
Cross-contamination may occur if insulin pens are shared among multiple patients. Steps should be taken to prohibit sharing of insulin pens.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alpha-Glucosidase Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with an alpha-glucosidase inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification
Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Beta-Blockers (Beta1 Selective): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Beta-Blockers (Nonselective): May enhance the hypoglycemic effect of Insulins. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Insulins. Risk C: Monitor therapy
Bortezomib: May enhance the therapeutic effect of Antidiabetic Agents. Bortezomib may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Chlorprothixene: May enhance the hypoglycemic effect of Insulins. Risk C: Monitor therapy
Dipeptidyl Peptidase-IV Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification
Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Edetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulins. Risk C: Monitor therapy
Etilefrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Glucagon-Like Peptide-1 Agonists: May enhance the hypoglycemic effect of Insulins. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Monitor patients for hypoglycemia. Risk D: Consider therapy modification
Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Herbal Products with Glucose Lowering Effects: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Liraglutide: May enhance the hypoglycemic effect of Insulins. Management: Consider reducing the liraglutide dose if coadministered with insulin. Prescribing information for the Saxenda brand of liraglutide recommends a dose decrease of 50%. Monitor blood glucose for hypoglycemia. Risk D: Consider therapy modification
Macimorelin: Insulins may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination
Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Metreleptin: May enhance the hypoglycemic effect of Insulins. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely for signs and symptoms of hypoglycemia. Risk D: Consider therapy modification
Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Pioglitazone: May enhance the adverse/toxic effect of Insulins. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination. Management: If insulin is combined with pioglitazone, consider insulin dose reductions to avoid hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure, and consider pioglitazone dose reduction or discontinuation if heart failure occurs Risk D: Consider therapy modification
Pramlintide: May enhance the hypoglycemic effect of Insulins. Management: Upon initiation of pramlintide, decrease mealtime insulin dose by 50% to reduce the risk of hypoglycemia. Monitor blood glucose frequently and individualize further insulin dose adjustments based on glycemic control. Risk D: Consider therapy modification
Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy
Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Rosiglitazone: Insulins may enhance the adverse/toxic effect of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination. Risk X: Avoid combination
Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification
Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Effective contraception is recommended for all patients under management for diabetes mellitus who could become pregnant, including those immediately postpartum. Pregnancy should be planned when optimal glycemic control is achieved (ADA 2023).
Insulin degludec can be detected in cord blood.
Based on available data, an increased risk of adverse pregnancy outcomes has not been observed following the use of insulin degludec in pregnant patients (Bonora 2018; Hiranput 2019; Keller 2019; Ringholm 2022).
Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major malformations, stillbirth, and macrosomia. To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2023; Blumer 2013).
Due to pregnancy-induced physiologic changes, insulin requirements tend to increase as pregnancy progresses, requiring frequent monitoring and dosage adjustments. Following delivery, insulin requirements decrease rapidly (ACOG 201 2018; ADA 2023). Due to the long half-life and duration of action of insulin degludec, omitting the first dose after delivery may help decrease the risk of maternal hypoglycemia immediately postpartum (Keller 2019).
Insulin is the preferred treatment of type 1 and type 2 diabetes mellitus in pregnancy, as well as gestational diabetes mellitus when pharmacologic therapy is needed. However, insulin degludec is not currently recommended to treat diabetes mellitus in pregnancy (ACOG 190 2018; ACOG 201 2018; Blumer 2013).
Both exogenous and endogenous insulin are present in breast milk (study not conducted with this preparation) (Whitmore 2012). Insulin is not systemically absorbed via breast milk but may provide local benefits to the infant GI tract (Anderson 2018).
Appropriate glycemic control is required for the establishment of lactation in patients with diabetes mellitus (Anderson 2018). Breastfeeding provides metabolic benefits to mothers with type 1, type 2, and gestational diabetes mellitus as well as their infants; therefore, breastfeeding is encouraged (ACOG 201 2018; ADA 2023; Blumer 2013). Breastfeeding also influences maternal glucose tolerance and may increase the risk of overnight hypoglycemia; close monitoring of patients treated with insulin is recommended as dose adjustments may be required (ADA 2023; Anderson 2018). A small snack before breastfeeding may help decrease the risk of hypoglycemia in patients with pregestational diabetes (ACOG 201 2018; Reader 2004). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.
Diabetes mellitus: Blood glucose (individualize frequency based on treatment regimen, hypoglycemia risk, and other patient-specific factors) (ADA 2023); electrolytes; renal function; hepatic function; weight.
Gestational diabetes mellitus: Blood glucose 4 times daily (1 fasting and 3 postprandial) until well controlled, then as appropriate (ACOG 2018).
Hospitalized patients: In patients who are eating, monitor blood glucose before meals and at bedtime; in patients who are not eating or are receiving continuous enteral feeds, monitor blood glucose every 4 to 6 hours (ADA 2023; ES [Umpierrez 2012]). More frequent monitoring may be required in some cases (eg, recurrent hypoglycemia, changes in nutrition, medication changes affecting glycemic control) (ES [Umpierrez 2012]).
HbA1c: Monitor at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; monitor quarterly in patients in whom treatment goals have not been met, or with therapy change. Note: In patients prone to glycemic variability (eg, patients with insulin deficiency), or in patients whose HbA1c is discordant with serum glucose levels or symptoms, consider evaluating HbA1c in combination with blood glucose levels and/or a glucose management indicator (ADA 2023; KDIGO 2020).
Recommendations for glycemic control in patients with diabetes:
Nonpregnant adults (AACE [Samson 2023], ADA 2023):
HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics). Note : In patients using a continuous glucose monitoring system, a goal of time in range >70% with time below range <4% is recommended and is similar to a goal HbA1c <7%.
Preprandial capillary blood glucose: 80 to 130 mg/dL (SI: 4.4 to 7.2 mmol/L) (more or less stringent goals may be appropriate based on patient-specific characteristics).
Peak postprandial capillary blood glucose (~1 to 2 hours after a meal): <180 mg/dL (SI: <10 mmol/L) (more or less stringent goals may be appropriate based on patient-specific characteristics).
Older adults (≥65 years of age) (ADA 2023):
Note: Consider less strict targets in patients who are using insulin and/or insulin secretagogues (sulfonylureas, meglitinides) (ES [LeRoith 2019]).
HbA1c: <7% to 7.5% (healthy); <8% (complex/intermediate health). Note: Individualization may be appropriate based on patient and caregiver preferences and/or presence of cognitive impairment. In patients with very complex or poor health (ie, limited remaining life expectancy), consider making therapy decisions based on avoidance of hypoglycemia and symptomatic hyperglycemia rather than HbA1c level.
Preprandial capillary blood glucose: 80 to 130 mg/dL (SI: 4.4 to 7.2 mmol/L) (healthy); 90 to 150 mg/dL (SI: 5 to 8.3 mmol/L) (complex/intermediate health); 100 to 180 mg/dL (SI: 5.6 to 10 mmol/L) (very complex/poor health).
Bedtime capillary blood glucose: 80 to 180 mg/dL (SI: 4.4 to 10 mmol/L) (healthy); 100 to 180 mg/dL (SI: 5.6 to 10 mmol/L) (complex/intermediate health); 110 to 200 mg/dL (SI: 6.1 to 11.1 mmol/L) (very complex/poor health).
Pregnant patients:
HbA1c: Pregestational diabetes (type 1 or type 2) (ADA 2023):
Preconception (patients planning for pregnancy): <6.5%.
During pregnancy <6% (if can be achieved without significant hypoglycemia) or <7% if needed to prevent hypoglycemia.
Capillary blood glucose: Note: Less stringent targets may be appropriate if goals cannot be achieved without causing significant hypoglycemia (ADA 2023).
Gestational diabetes mellitus (ACOG 2018; ADA 2023):
Fasting: <95 mg/dL (SI: <5.3 mmol/L).
Postprandial: <140 mg/dL (SI: <7.8 mmol/L) (at 1 hour) or <120 mg/dL (SI: <6.7 mmol/L) (at 2 hours).
Pregestational diabetes mellitus (type 1 or type 2) (ADA 2023 ):
Fasting: 70 to 95 mg/dL (SI: 3.9 to 5.3 mmol/L).
Postprandial: 110 to 140 mg/dL (SI: 6.1 to 7.8 mmol/L) (at 1 hour) or 100 to 120 mg/dL (SI: 5.6 to 6.7 mmol/L) (at 2 hours).
Hospitalized adult patients (ADA 2023): Target glucose range: 140 to 180 mg/dL (SI: 7.8 to 10 mmol/L) (majority of critically ill and noncritically ill patients; <140 mg/dL [SI: <7.8 mmol/L] may be appropriate for selected patients, if it can be achieved without excessive hypoglycemia). Initiate insulin therapy for persistent hyperglycemia at ≥180 mg/dL (SI: ≥10 mmol/L).
Perioperative care in adult patients (ADA 2023): Target glucose range during perioperative period: Consider targeting 80 to 180 mg/dL (SI: 4.4 to 10 mmol/L).
Children and adolescents:
Preprandial glucose: 70 to 130 mg/dL (SI: 3.9 to 7.2 mmol/L) (ISPAD [Dimeglio 2018]).
Postprandial glucose: 90 to 180 mg/dL (SI: 5 to 10 mmol/L) (ISPAD [Dimeglio 2018]).
Bedtime/overnight glucose: 80 to 140 mg/dL (SI: 4.4 to 7.8 mmol/L) (ISPAD [Dimeglio 2018]).
HbA1c: <7%; target should be individualized; a more stringent goal (<6.5%) may be reasonable if it can be achieved without significant hypoglycemia; less aggressive goals (<7.5% or <8%) may be appropriate in patients who cannot articulate symptoms of hypoglycemia, cannot check glucose frequently, have a history of severe hypoglycemia, or have extensive comorbid conditions (ADA 2023; ISPAD [Dimeglio 2018]).
Surgical patients (ISPAD [Jefferies 2018]):
Intraoperative: 90 to 180 mg/dL (SI: 5 to 10 mmol/L).
ICU, postsurgery: 140 to 180 mg/dL (SI: 7.8 to 10 mmol/L).
Classification of hypoglycemia (ADA 2023):
Level 1: 54 to 70 mg/dL (SI: 3 to 3.9 mmol/L); hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.
Level 2: <54 mg/dL (SI: <3 mmol/L); threshold for neuroglycopenic symptoms; requires immediate action.
Level 3: Hypoglycemia associated with a severe event characterized by altered mental and/or physical status requiring assistance.
Insulin acts via specific membrane-bound receptors on target tissues to regulate metabolism of carbohydrate, protein, and fats. Target organs for insulin include the liver, skeletal muscle, and adipose tissue.
Within the liver, insulin stimulates hepatic glycogen synthesis. Insulin promotes hepatic synthesis of fatty acids, which are released into the circulation as lipoproteins. Skeletal muscle effects of insulin include increased protein synthesis and increased glycogen synthesis. Within adipose tissue, insulin stimulates the processing of circulating lipoproteins to provide free fatty acids, facilitating triglyceride synthesis and storage by adipocytes; also directly inhibits the hydrolysis of triglycerides. In addition, insulin stimulates the cellular uptake of amino acids and increases cellular permeability to several ions, including potassium, magnesium, and phosphate. By activating sodium-potassium ATPases, insulin promotes the intracellular movement of potassium.
Normally secreted by the pancreas, insulin products are manufactured for pharmacologic use through recombinant DNA technology using either E. coli or Saccharomyces cerevisiae. Insulin degludec differs from human insulin by the omission of the amino acid threonine in position B-30 of the B-chain, and the subsequent addition of a side chain composed of glutamic acid and a C16 fatty acid. Insulins are categorized based on the onset, peak, and duration of effect (eg, rapid-, short-, intermediate-, and long-acting insulin). Insulin degludec is a long-acting, human insulin analog.
Note: Rate of absorption, onset, and duration of activity may be affected by site of injection, exercise, presence of lipodystrophy, local blood supply, and/or temperature.
Onset: ~1 hour
Protein binding: >99% (albumin)
Half-life elimination: ~25 hours (independent of dose)
Time to peak: 9 hours
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