Version May 2024
Dosage guidance:
Clinical considerations: Insulin detemir is a basal insulin. Insulin requirements vary between patients; monitor glucose levels frequently and individualize dose.
Diabetes mellitus, type 1, treatment:
Note: Insulin detemir 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 in divided doses; 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 detemir in a single daily dose or in 2 divided doses (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). In patients with inadequate basal insulin coverage with once-daily dosing, administration in 2 divided doses may be beneficial (Ref).
Preoperative dosage adjustment: Dose reductions are applied to the morning and/or evening insulin detemir doses as follows:
Evening scheduled dosage adjustment: SUBQ : Reduce insulin detemir 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).
Morning scheduled dosage adjustment : SUBQ: Administer one-half to two-thirds of the total morning insulin dose (basal + prandial) as insulin detemir 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 or 0.1 to 0.2 units/kg once daily in the evening or in 2 divided doses 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 2 to 3 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 patients using insulin detemir once daily, an alternative is to switch to a twice-daily regimen by administering the current daily dose in 2 equally divided doses (Ref); in patients close to glycemic targets, some experts administer ~80% of the current daily dose when switching to twice-daily dosing (Ref). In some patients, higher insulin detemir 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 : Dose reductions are applied to the morning and/or evening insulin detemir doses as follows:
Evening scheduled dosage adjustment: SUBQ: Reduce insulin detemir 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 scheduled dosage adjustment: SUBQ: For patients not using prandial insulin, reduce insulin detemir 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 detemir the morning of the procedure (Ref).
Hyperglycemia, hospitalized patients (off-label use):
Note: For use in patients with persistent hyperglycemia (eg, blood glucose ≥140 to 180 mg/dL for >12 to 24 hours) with or without a history of diabetes; patients with type 1 diabetes require basal insulin therapy regardless of glucose levels or nutritional intake. Dose is individualized; use of institution-specific protocols to achieve glycemic targets and minimize hypoglycemia is encouraged (Ref).
Initial:
Patients not receiving basal insulin prior to hospitalization: SUBQ: 0.1 to 0.3 units/kg administered once daily or in 2 divided doses (Ref). Note : Consider doses at the lower end of this range in patients ≥70 years of age and in those with renal impairment; consider doses at the higher end of this range in patients with glucose levels >200 mg/dL or who are receiving glucocorticoids (Ref).
Patients receiving basal insulin prior to hospitalization: SUBQ: Continue the prehospitalization basal insulin dose; an empiric 20% to 50% dose reduction may be considered in patients whose prehospitalization glucose levels were within target range, or in patients with impaired renal function, poor nutritional intake, or admission glucose levels <100 mg/dL; higher doses may be required in patients receiving glucocorticoids (Ref).
Patients transitioning from an IV insulin infusion: SUBQ: Refer to institution-specific protocols. In patients whose insulin requirements are known, prior basal insulin regimen may be resumed (Ref). In patients whose insulin requirements are not known, total daily dosage may be estimated as 60% to 80% of the mean IV insulin dosage over the prior 6 hours or by using weight-based dosing of 0.1 to 0.3 units/kg administered once daily (Ref). Note: Administer initial dose of basal insulin ≥2 to 4 hours before discontinuing IV insulin infusion (Ref).
Dosage adjustment: SUBQ: Adjust daily dose by 10% to 20% every 2 to 3 days to achieve glycemic targets (Ref). Consider reducing dosage for glucose levels <100 mg/dL to avoid hypoglycemia; in patients with glucose levels <40 mg/dL, larger dose reductions (eg, by 20% to 40%) may be needed (Ref).
Conversion from insulin glargine or NPH insulin to insulin detemir: SUBQ: Initial: May be substituted on an equivalent unit-per-unit basis; some patients with type 2 diabetes may require higher doses of insulin detemir than NPH insulin.
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 specific dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment may be needed as insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.
There are no specific dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment may be needed as 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 detemir: Pediatric drug information")
Dosage guidance:
Clinical considerations: Insulin detemir 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 detemir must be used in combination with a rapid or short-acting insulin. The daily doses presented are expressed as the total units/kg/day of all insulin formulations combined.
Insulin detemir-specific dosing: Note: All pediatric patients should have rapid-acting or regular insulin available for crisis management (Ref).
Initial dose: Children ≥2 years and Adolescents: SubQ: Approximately one-third to one-half of the total daily insulin requirement; a rapid-acting or short-acting insulin should also be used to complete the balance of the total daily insulin requirement. Adjust dosage according to patient response. If administered once daily, doses are generally administered with evening meals or at bedtime.
General insulin dosing:
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, obese, concomitant steroids, puberty, sedentary lifestyle, 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):
Infants ≥6 months and 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). In most type 1 patients, the use of a rapid-acting insulin analog is preferred over regular insulin to reduce hypoglycemia risk (Ref).
Dosage titration: 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 which most directly influences the blood glucose value in question, based on the known onset and duration of the insulin component.
Surgical patients (Ref): Note: Diabetic patients should be scheduled as the first case of the day.
Minor surgeries:
Morning procedure: Administer the usual insulin detemir 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 (>0.1 mmol/mol) production is present.
Afternoon procedure: Administer the usual morning dose of insulin detemir (if usually given in the morning).
Postprocedure: Once normal oral intake is achieved, resume usual insulin regimen; monitor closely; insulin requirement may be higher due to changes related to surgery (ie, postoperative stress, medication changes, inactivity).
Major surgeries:
Evening prior to surgery: If patient normally receives evening insulin doses, administer the usual evening and/or bedtime insulin detemir.
Morning of surgery: Omit morning insulin (short- and long-acting) and start IV insulin (regular) infusion and IV fluids containing dextrose at least 2 hours prior to surgery.
Postprocedure: Once normal oral intake is achieved, resume usual insulin regimen; monitor closely; insulin requirement may be higher due to changes related to surgery (ie, postoperative stress, medication changes, inactivity).
Diabetes mellitus, type 2: Note: The goal of therapy is to achieve an HbA1c <7% as quickly as possible using the safe titration of medications (Ref).
Insulin detemir-specific dosing: Children and Adolescents: SubQ: Initial: 0.1 to 0.2 units/kg/day once daily or divided twice daily.
General insulin dosing:
Newly diagnosed patients: Note: Recommended for use in metabolically unstable patients (eg, plasma glucose ≥250 mg/dL, HbA1c >8.5%, symptoms excluding acidosis) while metformin is initiated and titrated (Ref); may also be used for patients with ketosis/ketoacidosis/ketonuria to correct the hyperglycemia and the metabolic derangement (Ref).
Children ≥10 years and Adolescents: SubQ:
Initial therapy: 0.25 to 0.5 units/kg/dose once daily; titrate every 2 to 3 days as needed based on plasma glucose; use in combination with lifestyle changes and metformin to achieve goals.
Subsequent therapy:
Glycemic goal achieved: Once initial goal reached, insulin should be slowly tapered over 2 to 6 weeks by decreasing the insulin dose by 10% to 30% every few days and the patient transitioned to lowest effective doses or metformin monotherapy if able (Ref).
Failure to achieve glycemic goal: In patients who fail to achieve glycemic goals with insulin detemir (up to 1.5 units/kg/day) and maximum metformin dose, may consider dividing insulin detemir dose into multiple daily injections (eg, twice daily) and/or 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 (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, may consider dividing insulin detemir dose into multiple daily injections (eg, twice daily) and/or 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 (Ref).
Conversion from insulin glargine or NPH insulin: SubQ: May be substituted on an equivalent unit-per-unit basis; in one type 2 diabetes clinical trial, higher doses of insulin detemir were required than insulin NPH.
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 manufacturer's labeling; insulin requirements are reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.
There are no dosage adjustments provided in 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. Adverse reactions reported for monotherapy in children, adolescents, and adults unless otherwise specified.
>10%:
Endocrine & metabolic: Hypoglycemia (Type 1 combination regimens: adults: 82% to 88%; children and adolescents: 93% to 95%; Type 2 combination regimens: adults: 9% to 41%), severe hypoglycemia (Type 1 combination regimens: adults: 5% to 9%; children and adolescents: 2% to 16%; Type 2 combination regimens: adults: ≤2%)
Gastrointestinal: Abdominal pain (6% to 13%), gastroenteritis (6% to 17%)
Nervous system: Headache (14% to 31%)
Respiratory: Flu-like symptoms (6% to 14%), pharyngitis (10% to 17%), upper respiratory tract infection (26% to 36%)
1% to 10%:
Gastrointestinal: Nausea (children and adolescents: 7%), vomiting (children and adolescents: 7%)
Infection: Viral infection (children and adolescents: 7%)
Neuromuscular & skeletal: Back pain (adults: 8%)
Respiratory: Bronchitis (adults: 5%), cough (children and adolescents: 8%), rhinitis (children and adolescents: 7%)
Miscellaneous: Fever (children and adolescents: 10%)
<1%: Local: Pain at injection site
Frequency not defined:
Endocrine & metabolic: Weight gain
Immunologic: Antibody development
Postmarketing:
Endocrine & metabolic: Amyloidosis (localized cutaneous at injection site)
Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction
Hypersensitivity to insulin detemir 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: Hypersensitivity reactions (serious, life-threatening, and anaphylaxis) have occurred. If hypersensitivity reactions occur, discontinue administration and initiate supportive care measures.
• 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 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 2022).
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 detemir, although a clear solution, is NOT intended for IV or IM administration.
• Dosage adjustments: The duration of action of insulin detemir is dose-dependent; consider this factor during dosage adjustment and titration.
• Patient education: Diabetes self-management education is essential to maximize the effectiveness of therapy.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Subcutaneous:
Levemir: 100 units/mL (10 mL) [contains metacresol, phenol]
Solution Pen-injector, Subcutaneous:
Levemir FlexPen: 100 units/mL (3 mL) [contains metacresol, phenol]
Levemir FlexTouch: 100 units/mL (3 mL [DSC]) [contains metacresol, phenol]
No
Solution (Levemir Subcutaneous)
100 units/mL (per mL): $12.94
Solution Pen-injector (Levemir FlexPen Subcutaneous)
100 units/mL (per mL): $12.94
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. [DSC] = Discontinued product
Solution Cartridge, Subcutaneous:
Levemir Penfill: 100 units/mL (3 mL) [contains metacresol, phenol]
Solution Pen-injector, Subcutaneous:
Levemir FlexTouch: 100 units/mL ([DSC]) [contains metacresol, phenol]
SUBQ: Do not administer IM or IV; for SUBQ administration only. Do not use if solution is viscous or cloudy; use only if clear and colorless with no visible particles. Insulin detemir should be administered once or twice daily. When given once daily, administer with the evening meal or at bedtime. When given twice daily, administer the evening dose with the evening meal, at bedtime, or 12 hours following the morning dose. SUBQ administration is usually made into the thighs, upper arms, or abdomen; absorption rates vary amongst injection sites; be consistent with area used while rotating injection sites within the same region to avoid 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. Do not dilute or mix insulin detemir with any other insulin formulation or solution; not recommended for use in external SUBQ insulin infusion pump. For prefilled pen devices, prime the needle before each injection with 2 units of insulin (use a new needle for each injection). Once 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.
Parenteral: SUBQ: Do not use if solution is viscous or cloudy; use only if clear and colorless with no visible particles. For subcutaneous administration only. Do not administer IM or IV. Administer once or twice daily. When administered once daily, give with evening meal or at bedtime. When administered twice daily, give evening dose with evening meal, at bedtime, or 12 hours following the morning dose. Avoid cold injections. SUBQ administration is usually made into the thighs, upper arms, or abdomen; rotate injection sites within the same region to avoid 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. Do not dilute or mix insulin detemir with any other insulin formulation or solution. Not for IV infusion or use in insulin infusion pumps.
Prefilled pen: Levemir FlexTouch prefilled pens will administer up to 80 units per injection in 1-unit increments. Prior to each injection, the needle must be primed 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 dose dial returns to 0, continue to hold the needle in the skin for 6 seconds to ensure the full dose has been administered. Do not rub the area. If dose is >80 units, >1 injection will be required; split dose and administer in multiple injections. Do not mix other insulin formulations with insulin detemir contained in a prefilled pen.
Diabetes mellitus, types 1 and 2, treatment: Treatment of type 1 diabetes mellitus and type 2 diabetes mellitus to improve glycemic control.
Hyperglycemia in hospitalized patients
Levemir may be confused with Lovenox
The Institute for Safe Medication Practices (ISMP) includes this medication among its list 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 detemir is a clear solution, but it is NOT intended for IV or IM administration.
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
Patients with diabetes who wish to conceive should use adequate contraception until glycemic control is achieved (ADA 2022). Patients successfully using long-acting insulin detemir prior to conception may continue use (Blumer 2013).
Insulin detemir can be detected in cord blood.
An increased risk of fetal abnormalities has not been observed following the use of insulin detemir in pregnant patients with type 1 diabetes mellitus.
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 (ACOG 201 2018). 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 2022; 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 2022).
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 (ACOG 190 2018; ACOG 201 2018; ADA 2022). Pregnancy outcomes are similar following maternal use of insulin detemir and NPH insulin in pregnant patients with type 1 diabetes mellitus. Outcomes are likely to be similar in pregnant patients with type 2 diabetes and insulin detemir may be used when clinically appropriate (ACOG 201 2018). Patients may be switched to insulin detemir during pregnancy when NPH insulin is not adequate (Blumer 2013).
Patients successfully using long-acting insulin detemir prior to conception may continue use during pregnancy (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 2022; Blumer 2013). Breastfeeding also influences maternal glucose tolerance; close monitoring of patients treated with insulin is recommended as dose adjustments may be required (ADA 2022; 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 2022); 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 2022; 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 2022; KDIGO 2020).
Recommendations for glycemic control in patients with diabetes and/or hyperglycemia:
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 2022): 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).
Perioperative care in adult patients (ADA 2022): 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 detemir differs from human insulin by the omission of threonine in position B30 and the addition of a C14 fatty acid chain to the amino acid located at position B29. Insulins are categorized based on the onset, peak, and duration of effect (eg, rapid-, short-, intermediate-, and long-acting insulin).
Note: Onset and duration of hypoglycemic effects depend upon the route of administration (absorption and onset of action are more rapid after deeper IM injections than after SUBQ), site of injection (onset and duration are progressively slower with SUBQ injection into the abdomen, arm, buttock, or thigh respectively), volume and concentration of injection, and the preparation administered. Rate of absorption, onset, and duration of activity may be affected by exercise, presence of lipodystrophy, local blood supply, and/or temperature.
Onset of action: 3 to 4 hours.
Peak effect: 3 to 9 hours (Plank 2005).
Duration: Dose dependent: 6 to 23 hours; Note: At lower dosages (0.1 to 0.2 units/kg), mean duration is variable (5.7 to 12.1 hours). At 0.4 units/kg, the mean duration was 19.9 hours. At high dosages (≥0.8 units/kg) the duration is longer and less variable (mean of 22 to 23 hours) (Plank 2005).
Distribution: Vd: 0.1 L/kg.
Protein binding: >98% (albumin).
Bioavailability: 60%.
Half-life elimination: 5 to 7 hours (dose-dependent).
Time to peak, plasma: 6 to 8 hours.
Altered kidney function: Insulin clearance may be reduced in patients with impaired renal function.
Pediatric: AUC and Cmax were higher by 10% and 24%, respectively, in children (6 to 12 years of age) compared with adolescents and adults.
Older adult: The AUC was 35% higher in healthy elderly patients (≥68 years of age) compared with younger patients (25 to 35 years of age) because of reduced clearance in elderly patients.
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