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Insulin Detemir

Medically reviewed by Drugs.com. Last updated on Jul 7, 2020.

Pronunciation

(IN soo lin DE te mir)

Index Terms

  • Detemir Insulin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous:

Levemir: 100 units/mL (10 mL) [contains metacresol, phenol]

Solution Pen-injector, Subcutaneous:

Levemir FlexTouch: 100 units/mL (3 mL) [contains metacresol, phenol]

Brand Names: U.S.

  • Levemir
  • Levemir FlexTouch

Pharmacologic Category

  • Insulin, Long-Acting

Pharmacology

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).

Distribution

Vd: 0.1 L/kg

Excretion

Urine

Onset of Action

3 to 4 hours; Peak effect: 3 to 9 hours (Plank 2005)

Time to Peak

Plasma: 6 to 8 hours

Duration of Action

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).

Half-Life Elimination

5 to 7 hours (dose-dependent)

Protein Binding

98% (albumin)

Special Populations: Renal Function Impairment

Insulin Cl may be reduced in patients with impaired renal function.

Special Populations: Elderly

The AUC was 35% higher in healthy elderly patients (68 y and older) compared with younger patients (25 to 35 y of age) because of reduced Cl in elderly patients. Higher insulin detemir AUC levels in elderly patients because of reduced Cl.

Special Populations: Children

AUC and Cmax were higher by 10% and 24%, respectively, in children (6 to 12 y of age) compared with adolescents and adults.

Use: Labeled Indications

Diabetes mellitus, types 1 and 2, treatment: Treatment of type 1 diabetes mellitus and type 2 diabetes mellitus to improve glycemic control.

Contraindications

Hypersensitivity to insulin detemir or any component of the formulation; during episodes of hypoglycemia.

Documentation of allergenic cross-reactivity for insulin is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Note: Insulin detemir is a long-acting insulin. Insulin requirements vary dramatically between patients and dictates frequent monitoring and close medical supervision.

Diabetes mellitus, type 1, treatment: SubQ:

Note: Insulin detemir must be used concomitantly with rapid- or short-acting insulins (ie, multiple daily injection regimen). The total daily doses (TDD) presented below are expressed as the total units/kg/day of all insulin formulations combined.

General insulin dosing:

Initial TDD: ~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 the potential for hypoglycemia; higher initial doses may be required in patients who are obese, sedentary, or presenting with ketoacidosis (AACE/ACE [Handelsman 2015]; ADA 2020).

Usual TDD maintenance range: 0.4 to 1 units/kg/day in divided doses (ADA 2020).

Division of TDD (multiple daily injections):

Basal insulin: Generally, 40% to 50% of the TDD is given as basal insulin (intermediate or long acting) (AACE/ACE [Handelsman 2015]; ADA 2020). Insulin detemir may be administered as a single dose or in two divided doses daily.

Prandial insulin: The remaining portion (ie, 50% to 60%) of the TDD is then divided and administered before, at, or just after mealtimes, depending on the formulation (eg, short, rapid, or ultra-rapid acting) (AACE/ACE [Handelsman 2015]; ADA 2020).

Dosage adjustment: Dosage must be titrated to achieve glucose control and avoid hypoglycemia. Adjust dose to maintain premeal and bedtime glucose in target range. 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. Treatment and monitoring regimens must be individualized. To minimize hypoglycemia risk, basal insulins are generally titrated once or twice weekly (eg, every 3 to 7 days) (ADA 2020; McCall 2012).

Diabetes mellitus, type 2, treatment: SubQ:

Note: May be initiated in patients with severe or symptomatic hyperglycemia (eg, HbA1c ≥10%, blood glucose ≥300 mg/dL, presence of polyuria/polydipsia), or who have inadequate glycemic control on metformin ± other noninsulin agents (ADA 2020). Consider a dose reduction (eg, by 50%) or discontinuation of insulin secretagogue when initiating insulin therapy (ADA/EASD [Davies 2018]).

Initial:10 units (or 0.1 to 0.2 units/kg) once daily in the evening or in 2 divided doses (ADA 2020; manufacturer’s labeling). If HbA1c >8% prior to initiation of basal insulin, 0.2 to 0.3 units/kg/day is recommended (AACE/ACE [Garber 2020]).

Dosage adjustment:

For elevated fasting plasma glucose: Adjust dose using evidence-based titration algorithm (eg, by 2 units every 3 days) while avoiding hypoglycemia.

For elevated HbA1c despite achieving fasting plasma glucose target: Consider intensification of therapy with additional agents that target postprandial glucose rather than continuing to increase the insulin detemir dose; higher insulin detemir doses (eg, >0.5 units/kg/day) may provide only diminishing improvements in HbA1c (AACE/ACE [Garber 2020]; ADA 2020).

For hypoglycemia: If no clear reason for hypoglycemia, decrease dose by 10% to 20% (ADA 2020); for severe hypoglycemia (ie, requiring assistance from another person or blood glucose <40 mg/dL), reduce dose by 20% to 40% (AACE/ACE [Garber 2020]).

Dosage adjustment when adding prandial insulin: Consider reducing the basal insulin dose by 4 units (or ~10%) if HbA1c is <8% when initiating prandial insulin (ADA 2020).

Patients with diabetes receiving enteral feedings (ADA 2020): Note: TDD of insulin is divided into a basal component (intermediate- or long-acting insulin) and nutritional and correctional components (regular insulin or rapid-acting insulins).

Basal component: SubQ: Continue previous basal insulin dose or administer 30% to 50% of current TDD as insulin detemir; if basal insulin naive, administer insulin detemir 5 units every 12 hours.

Patients with diabetes undergoing surgery: SubQ: On the morning of surgery or procedure, reduce the usual dose by 10% to 50% if patient will be fasting or is at high risk of hypoglycemia (ADA 2020; Umpierrez 2012; Pichardo-Lowden 2012).

Conversion from insulin glargine or NPH insulin to insulin detemir: Initial: May be substituted on an equivalent unit-per-unit basis; some patients with type 2 diabetes may require higher doses of detemir than NPH.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: 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.

Type 1 diabetes mellitus: Children and Adolescents: Note: For basal insulin coverage, long-acting insulin analogs are preferred over insulin NPH due to decreased risk of hypoglycemia (AACE/ACE [Handelsman 2015]; ADA 2020; ADA [Chiang 2014]). 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 (ISPAD [Danne 2018]).

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 (AACE/ACE [Handelsman 2015]; ADA 2020); usual range: 0.4 to 1 units/kg/day in divided doses (AACE/ACE [Handelsman 2015]; ADA 2020; Silverstein 2005); lower doses (0.25 units/kg/day) may be used, especially in young children, to avoid potential hypoglycemia (Beck 2015); higher doses may be necessary for some patients (eg, obese, concomitant steroids, puberty, sedentary lifestyle, following diabetic ketoacidosis presentation) (AACE/ACE [Handelsman 2015]; ADA 2020; Silverstein 2005).

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 (ISPAD [Danne 2018]; ISPAD [Sundberg 2017]).

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 (AACE/ACE [Handelsman 2015]; ADA 2020; ISPAD [Danne 2018]; Peters 2013).

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 (AACE/ACE [Handelsman 2015]; ADA 2020; ADA [Chiang 2014]; ISPAD [Danne 2018]).

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 (ISPAD [Jefferies 2018]): 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).

Type 2 diabetes mellitus: Note: The goal of therapy is to achieve an HbA1c <7% as quickly as possible using the safe titration of medications (AAP [Copeland 2013]; ADA 2020; ISPAD [DiMeglio 2018]; ISPAD [Zeitler 2018]).

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 (ADA [Arslanian 2018]; ADA 2020); may also be used for patients with ketosis/ketoacidosis/ketonuria to correct the hyperglycemia and the metabolic derangement (ADA [Arslanian 2018]; ISPAD [Zeitler 2018]).

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 (AAP [Copeland 2013]; ADA 2020; ADA [Arslanian 2018]; ISPAD [Zeitler 2018]).

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) (ADA [Arslanian 2018]; ISPAD [Zeitler 2018]). 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 (ADA [Arslanian 2018]).

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 (ADA [Arslanian 2018]).

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) (ADA [Arslanian 2018]; ISPAD [Zeitler 2018]). 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 (ADA [Arslanian 2018]).

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.

Administration

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 Levemir FlexTouch pen, prime the needle before each injection with 2 units of insulin (use a new needle for each injection). Once injected, hold the pen device in the skin for a count of 6 after the dose dial has returned to 0 units before removing the needle to ensure the full dose has been administered.

Dietary Considerations

Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.

Storage

Unopened vials, cartridges, and prefilled pens may be stored under refrigeration between 2°C and 8°C (36°F to 46°F) until the expiration date or at room temperature <30°C (<86°F) for 42 days; do not freeze; keep away from heat and sunlight. Once punctured (in use), vials may be stored under refrigeration or at room temperature <30°C (<86°F); use within 42 days. Cartridges and prefilled pens that have been punctured (in use) should be stored at temperatures <30°C (<86°F) and used within 42 days; do not freeze or refrigerate.

Drug Interactions

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. Consider therapy modification

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Exceptions: Danazol. Monitor therapy

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Beta-Blockers: May enhance the hypoglycemic effect of Insulins. Exceptions: Levobunolol; Metipranolol. 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. Consider therapy modification

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Edetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulins. 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. Exceptions: Liraglutide. Consider therapy modification

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. 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. Consider therapy modification

Macimorelin: Insulins may diminish the diagnostic effect of Macimorelin. Avoid combination

Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. 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. Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. 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 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. Consider therapy modification

Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. 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. Monitor therapy

Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. 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. Avoid combination

Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. 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. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Adverse Reactions

>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 (adults: 6%; children and adolescents: 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: Immunologic: Antibody development

Postmarketing: Endocrine & metabolic: Amyloidosis (localized cutaneous at injection site)

Warnings/Precautions

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 2013). 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 with diabetes: Exclusive use of a sliding scale insulin regimen (insulin regular) in the inpatient hospital 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 or basal plus bolus is preferred. In noncritically ill patients with adequate nutritional intake, a combination of basal insulin, nutritional, and correction components 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 2020).

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.

Monitoring Parameters

Diabetes mellitus: Plasma glucose (typically before meals and snacks and at bedtime; occasionally additional monitoring may be required [ADA 2020]), electrolytes, HbA1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2020]), potassium (in patients at risk for hypokalemia); 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 190 2018).

Reproductive Considerations

Females with diabetes who wish to conceive should use adequate contraception until glycemic control is achieved (ADA 2020). Females successfully using long acting insulin detemir prior to conception may continue use (Blumer 2013).

Pregnancy Considerations

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 females 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 birth defects, 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 2020; 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 2020).

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 2020). Pregnancy outcomes are similar following maternal use of insulin detemir and NPH insulin in pregnant females with type 1 diabetes mellitus. Outcomes are likely to be similar in pregnant females with type 2 diabetes and insulin detemir may be used when clinically appropriate (ACOG 201 2018). Females may be switched to insulin detemir during pregnancy when NPH insulin is not adequate (Blumer 2013).

Females successfully using long acting insulin detemir prior to conception may continue use during pregnancy (Blumer 2013).

Patient Education

What is this drug used for?

• It is used to lower blood sugar in patients with high blood sugar (diabetes).

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Injection site irritation

• Common cold symptoms

• Throat irritation

• Flu-like symptoms

• Headache

• Abdominal pain

• Nausea

• Vomiting

• Back pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating.

• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat.

• Blurred vision

• Chills

• Severe dizziness

• Passing out

• Mood changes

• Seizures

• Slurred speech

• Shortness of breath

• Excessive weight gain

• Swelling of arms or legs

• Injection site thick skin, pits, or lumps

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.