(IN soo lin DE te mir)
- Detemir Insulin
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Levemir: 100 units/mL (10 mL) [contains metacresol, phenol]
Solution Pen-injector, Subcutaneous:
Levemir FlexPen: 100 units/mL (3 mL [DSC]) [contains metacresol, phenol]
Levemir FlexTouch: 100 units/mL (3 mL) [contains metacresol, phenol]
Brand Names: U.S.
- Levemir FlexPen [DSC]
- Levemir FlexTouch
- Insulin, Long-Acting
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).
Vd: 0.1 L/kg
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: Duration is dose-dependent. 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).
5 to 7 hours (dose-dependent)
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
Treatment of type 1 diabetes mellitus (insulin dependent, IDDM) and type 2 diabetes mellitus (noninsulin dependent, NIDDM) to improve glycemic control
Hypersensitivity to insulin detemir or any component of the formulation
Diabetes mellitus: Note: Insulin detemir is a long-acting insulin administered by SubQ injection. When compared to insulin NPH, insulin detemir has slower, more prolonged absorption; duration of activity is dose-dependent. Insulin detemir may be given once or twice daily when used as the basal insulin component of therapy. Changing the basal insulin component from another insulin to insulin detemir can be done on a unit-to-unit basis. Insulin requirements vary dramatically between patients and dictate frequent monitoring and close medical supervision.
Diabetes mellitus, type 1: SubQ:
Note: Multiple daily doses are utilized and guided by blood glucose monitoring. Combinations of insulin formulations are commonly used. The daily doses presented below are expressed as the total units/kg/day of all insulin formulations combined.
Initial dose: Approximately one-third of the total daily insulin requirement given as insulin detemir administered in 1 to 2 divided doses. A rapid- or short-acting insulin should be used to complete the balance (~2/3) of the total daily insulin requirement.
Conversion from insulin glargine or NPH insulin: 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.
General insulin dosing:
Usual maintenance range: 0.5 to 1 units/kg/day in divided doses. An estimate of anticipated needs may be based on body weight and/or activity factors as follows:
Nonobese: 0.4 to 0.6 units/kg/day
Obese: 0.8 to 1.2 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 (IDF-ISPAD 2011).
Division of daily insulin requirement ("conventional therapy"): Generally, 50% to 75% of the total daily dose (TDD) is given as an intermediate-acting or a long-acting form of insulin (in 1 to 2 daily injections). The remaining portion of the TDD is then divided and administered before or at mealtimes (depending on the formulation) as a rapid-acting or short-acting form of insulin.
Division of daily insulin requirement ("intensive therapy"): Basal insulin delivery with 1 or 2 doses of intermediate-acting or long-acting insulin formulations superimposed with doses of short- or rapid-acting insulin formulations 3 or more times daily.
Adjustment of dose: 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. Also see Additional Information or Pharmacotherapy Pearls.
Diabetes mellitus, type 2: SubQ:
Inadequately controlled on oral antidiabetic agents: Initial: 10 units (or 0.1 to 0.2 units/kg) once daily in the evening; may also administer total daily dose in 2 divided doses.
Inadequately controlled on GLP-1 receptor agonist: Initial: 10 units once daily in the evening.
Conversion from insulin glargine or NPH insulin: Initial: 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.
General considerations for insulin use in type 2 diabetes:
Timing of initiation: The goal of therapy is to achieve an HbA1c <7%. According to a position statement by the ADA and European Association for the Study of Diabetes (EASD), dual therapy (metformin + a second antihyperglycemic agent) is recommended in patients with type 2 diabetes who fail to achieve glycemic goals after ~3 months with lifestyle interventions and metformin monotherapy (unless contraindications to metformin exist). Preference is not given for adding insulin or a noninsulin agent as the second antihyperglycemic agent (drug choice should be individualized based on patient characteristics). However, insulin should be considered as part of a combination regimen when hyperglycemia is severe, particularly if patient is symptomatic or has catabolic features (eg, weight loss, ketosis). If insulin is selected, the addition of basal insulin (ie, a long-acting insulin such as glargine or detemir) is recommended. If HbA1c target not achieved after ~3 months of dual therapy, may proceed to triple therapy (Inzucchi 2015). If HbA1c >8% prior to initiation of basal insulin, 0.2 to 0.3 units/kg once daily is recommended (Garber [AACE/ACE 2016]).
Intensification of therapy: If HbA1c target has not been met, despite titrating basal insulin (ie, long-acting insulin) to provide acceptable fasting blood glucose concentrations, intensification of therapy should be considered to cover postprandial glucose excursions. Options include: adding a mealtime insulin (1 to 3 injections of a rapid-acting insulin analog [lispro, aspart, glulisine]) or adding a GLP-1 receptor agonist (eg, exenatide, liraglutide). Alternatively, although less studied, may transition from basal insulin (ie, long-acting insulin) to a twice daily premixed (or biphasic) insulin analog (70/30 aspart mix, 75/25 or 50/50 lispro mix) (Inzucchi 2015).
Refer to adult dosing.
Diabetes mellitus, type 1: Children ≥2 years and Adolescents: Refer to adult dosing.
Dosing: Renal Impairment
No dosage adjustment provided in manufacturer’s labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.
Dosing: Hepatic Impairment
No dosage adjustment provided in manufacturer’s labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.
Refer to indication-specific dosing for obesity-related information (may not be available for all indications).
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. Cold injections should be avoided. SubQ administration is usually made into the thighs, arms, or abdomen; rotate injection sites within the same region to avoid lipodystrophy. Do not dilute or mix insulin detemir with any other insulin formulation or solution; not recommended for use in external SubQ insulin infusion pump.
Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.
Compatibility in syringe: Incompatible with insulin aspart, insulin glargine, insulin glulisine, insulin lispro, insulin NPH, insulin regular.
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.
Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. 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 Insulin. Exceptions: Levobunolol; Metipranolol. Monitor therapy
DPP-IV Inhibitors: May enhance the hypoglycemic effect of Insulin. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Edetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulin. Monitor therapy
Edetate Disodium: May enhance the hypoglycemic effect of Insulin. Monitor therapy
GLP-1 Agonists: May enhance the hypoglycemic effect of Insulin. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Avoid the use of lixisenatide in patients receiving both basal insulin and a sulfonylurea. Exceptions: Liraglutide. Consider therapy modification
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 Insulin. Management: If liraglutide is used for the treatment of diabetes (Victoza), consider insulin dose reductions. The combination of liraglutide and insulin should be avoided if liraglutide is used exclusively for weight loss (Saxenda). Consider therapy modification
MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Metreleptin: May enhance the hypoglycemic effect of Insulin. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely. Consider therapy modification
Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Pioglitazone: May enhance the adverse/toxic effect of Insulin. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination. Management: If insulin is combined with pioglitazone, dose reductions should be considered to reduce the risk of hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure. Consider therapy modification
Pramlintide: May enhance the hypoglycemic effect of Insulin. 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
Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy
Rosiglitazone: Insulin 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 Blood Glucose Lowering Agents. Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
SGLT2 Inhibitors: May enhance the hypoglycemic effect of Insulin. 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
Central nervous system: Headache (adults: 7% to 23%, children: 31%)
Endocrine & metabolic: Hypoglycemia (Type 1 combination regimens: children & adolescents: 93% to 95%, adults: 82% to 88%; Type 2 combination regimens: adults: 9% to 41%), severe hypoglycemia (Type 1 combination regimens: children & adolescents: 2% to 16%; adults 5% to 9%; Type 2 combination regimens: adults: ≤2%)
Gastrointestinal: Gastroenteritis (children & adolescents: 17%), abdominal pain (6%; children & adolescents: 13%)
Respiratory: Upper respiratory tract infection (13% to 26%; children & adolescents: 36%), pharyngitis (10%; children & adolescents: 17%), flu-like symptoms (8%; children & adolescents: 14%)
1% to 10%:
Gastrointestinal: Nausea (children & adolescents: 7%), vomiting (children & adolescents: 7%)
Infection: Viral infection (children & adolescents: 7%)
Respiratory: Cough (children & adolescents: 8%), rhinitis (children & adolescents: 7%)
Miscellaneous: Fever (children & adolescents: 10%)
<1%, postmarketing, and/or case reports: Pain at injection site
Concerns related to adverse effects:
• Anaphylactoid/hypersensitivity reactions: Allergic reactions, including anaphylaxis, may occur with insulin products.
• Hypoglycemia: The most common adverse effect of insulin is hypoglycemia. The timing of hypoglycemia differs among various insulin formulations. Hypoglycemia may result from increased work or exercise without eating; use of long-acting insulin preparations (eg, insulin detemir, insulin glargine) may delay recovery from 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.
• 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.
• Diabetic ketoacidosis (DKA): Should not be used in patients with DKA; use of an IV rapid acting or short acting insulin is preferred.
• 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.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
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).
• Administration: Insulin detemir, although a clear solution, is NOT intended for IV or IM administration.
• Appropriate use: Diabetes mellitus: The general objective of exogenous insulin therapy is to approximate the physiologic pattern of insulin secretion which is characterized by two distinct phases. Phase 1 insulin secretion suppresses hepatic glucose production and phase 2 insulin secretion occurs in response to carbohydrate ingestion; therefore, exogenous insulin therapy may consist of basal insulin (eg, intermediate- or long-acting insulin), insulin administered via continuous subcutaneous insulin infusion [CSII]) and/or preprandial insulin (eg, short- or rapid-acting insulin) (see Related Information: Insulin Products). Patients with type 1 diabetes do not produce endogenous insulin; therefore, these patients require both basal and preprandial insulin administration. Patients with type 2 diabetes retain some beta-cell function in the early stages of their disease; however, as the disease progresses, phase 1 insulin secretion may become completely impaired and phase 2 insulin secretion becomes delayed and/or inadequate in response to meals. Therefore, patients with type 2 diabetes may be treated with oral antidiabetic agents, basal insulin, and/or preprandial insulin depending on the stage of disease and current glycemic control. Since treatment regimens often consist of multiple agents, dosage adjustments must address the specific phase of insulin release that is primarily contributing to the patient’s impaired glycemic control. Treatment and monitoring regimens must be individualized.
• 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 (DSME) is essential to maximize the effectiveness of therapy.
Diabetes mellitus: Plasma glucose, 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 2016a]), lipid profile, renal function
Pregnancy Risk Factor
Dose-related adverse events were observed in animal reproduction studies. Insulin detemir has been detected in cord blood. An increased risk of fetal abnormalities has not been observed following the use of insulin detemir in pregnancy; pregnancy outcomes are similar following maternal use of insulin detemir and NPH insulin.
In women with diabetes, maternal hyperglycemia can be associated with congenital malformations as well as adverse effects in the fetus, neonate, and the mother (ACOG 2005; ADA 2016d; Kitzmiller 2008; Metzger 2007). 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 (ACOG 2013; ADA 2016d; Blumer 2013; Kitzmiller 2008; Lambert 2013). Prior to pregnancy, effective contraception should be used until glycemic control is achieved (ADA 2016d; Kitzmiller 2008).
Insulin requirements tend to fall during the first trimester of pregnancy and increase in the later trimesters, peaking at 28 to 32 weeks of gestation. Following delivery, insulin requirements decrease rapidly (ACOG 2005). Women who are stable on insulin detemir prior to conception may continue it during pregnancy. Pregnant women may also be switched to insulin detemir during pregnancy when therapy with NPH insulin is not adequate (Blumer 2013).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Have patient report immediately to prescriber signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), severe injection site irritation, blurred vision, vision changes, chills, severe dizziness, passing out, mood changes, seizures, slurred speech, shortness of breath, excessive weight gain, swelling of arms or legs, or change in skin to thick or thin at injection site (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
More about insulin detemir
- Other brands: Levemir