Insulin Detemir (Monograph)
Brand name: Levemir
Drug class: Long-acting Insulins
Warning
Inuslin Detemir is no longer commercially available in the U.S; supplies of the drug are available until the end of 2024. See the FDA website (https://www.accessdata.fda.gov/scripts/cder/daf/) for information on drugs that have been discontinued.
Introduction
Because this drug is no longer available in the U.S. market, the material in this section is no longer updated by AHFS DI. If this drug is used in countries other than the U.S., it is essential that the manufacturers’ labeling be consulted for more recently available information.
Antidiabetic agent; long acting human insulin analog synthesized using recombinant DNA technology in Saccharomyces cerevisiae then chemically modified.1 18
Uses for Insulin Detemir
Because this drug is no longer available in the U.S. market, the material in this section is no longer updated by AHFS DI. If this drug is used in countries other than the U.S., it is essential that the manufacturers’ labeling be consulted for more recently available information.
Diabetes Mellitus
Treatment of type 1 diabetes mellitus in adults and children ≥2 years of age or type 2 diabetes mellitus in adults who require long-acting (basal) insulin to improve glycemic control.1 2 3 4 5 30 36
Not indicated for the treatment of diabetic ketoacidosis; short-acting IV insulins (e.g., regular insulin) are preferred.1 17 18 20
At least as effective for glycemic control in adults as isophane insulin human or insulin glargine.1 2 3 7 16 18
May be associated with less interindividual variability in fasting blood glucose concentration,2 7 10 16 17 22 23 lower risk for hypoglycemia,2 7 16 17 22 23 and a lower risk of weight gain1 2 7 16 17 22 than isophane insulin human.17 18 May provide advantages over isophane insulin human in patients who have had difficulty achieving adequate glycemic control without frequent hypoglycemic episodes and/or those at high risk of hypoglycemia, particularly nocturnal hypoglycemia.16 17 23
Related/similar drugs
metformin, Trulicity, Lantus, Tresiba, Victoza, Levemir, Novolog
Insulin Detemir Dosage and Administration
Administration
Because this drug is no longer available in the U.S. market, the material in this section is no longer updated by AHFS DI. If this drug is used in countries other than the U.S., it is essential that the manufacturers’ labeling be consulted for more recently available information.
Administer by sub-Q injection.1 18 Do not administer IV or IM or via insulin infusion pump.1 6 17
IV administration may cause severe hypoglycemia.1 17
Do not mix with any other insulin.1 6 7 17 18
Inspect visually prior to administration and use only if solution appears clear and colorless.1
Sub-Q Administration
Administer by sub-Q injection once or twice daily using a conventional insulin syringe or an injection pen (i.e., FlexTouch).1 8 Use FlexTouch device only with NovoFine, NovoFine Plus, or NovoTwist needles.8
Consult labeling accompanying the injection device for proper assembly, administration, and care of injection pen.1 8 18
Administer into thigh, abdominal wall, or upper arm.1 Follow a planned rotation of injection sites within an injection area.1
Once-daily regimen: Administer the daily dose with the evening meal or at bedtime.1 7 Has been administered once daily in the morning† [off-label] in patients with type 2 diabetes mellitus.18 21
Twice-daily regimen: Administer the first dose in the morning and the second dose after the evening meal, at bedtime, or 12 hours after the morning dose.1 3 7
Concomitant use with a glucagon-like peptide-1 (GLP-1) receptor agonist: Administer each drug as a separate injection (may inject into same body region but not adjacent to each other); do not mix.1
Dosage
Dosage of insulin detemir is expressed in terms of units.1
Individualize dosage based on blood glucose determinations to obtain optimum therapeutic effect.1 Glucose monitoring is recommended for all patients with diabetes mellitus.1
Closely monitor blood glucose concentrations during insulin initiations and transitions and in the initial weeks thereafter.1 Adjust dosage and timing of insulins and/or other concomitant antidiabetic agents as needed to achieve glycemic goals.1 18
Make any dosage change cautiously and only under medical supervision.1 If insulin therapy is changed (e.g., strength, timing of dosing, manufacturer, type, or method of administration), may require adjustments in dosage of insulin detemir or concomitant antidiabetic agents.1 2
May require insulin dosage adjustment if patient changes usual physical activity or meal plan, or during times of illness, emotional disturbances, or stress.1
Pediatric Patients
Diabetes Mellitus
Children ≥2 years of age: No specific dosage recommendations by manufacturer.1 When used with mealtime sub-Q insulin, basal insulin requirements (e.g., insulin detemir) should comprise approximately one-third of the total daily insulin dosage, with the remainder given preprandially as rapid- or short-acting insulin.1
Type 1
Sub-QChildren ≥2 years of age: Initial total daily insulin dosages generally range from 0.2–1 unit/kg.b c e f k l
Transferring from Other Insulin Therapy
Sub-QChildren ≥2 years of age, from combination therapy with intermediate- or long-acting insulin and short- or rapid-acting insulin: Initial dosage of insulin detemir is identical (unit-for-unit basis) to the dosage of the longer-acting insulin.1
Children ≥2 years of age, from basal insulin only: Initial dosage of insulin detemir is identical (unit-for-unit basis) to the dosage of basal insulin.1
Adults
Diabetes Mellitus
When used with mealtime sub-Q insulin, basal insulin requirements (e.g., insulin detemir) should comprise approximately one-third of the total daily insulin dosage, with the remainder given preprandially as rapid- or short-acting insulin.1
Insulin-naive Patients
Sub-QType 1 diabetes mellitus: Initial total daily insulin dosages generally range from 0.2–1 unit/kg.b c e f k l
Type 2 diabetes mellitus inadequately controlled on oral antidiabetic agents: Initial dosage is 0.1–0.2 units/kg once daily in the evening or 10 units once daily in the evening or divided into a twice-daily regimen.1
Type 2 diabetes mellitus inadequately controlled with a GLP-1 receptor agonist: Initial dosage is 10 units given once daily in the evening.1 Dosage reduction or more conservative titration of insulin detemir may be required to minimize risk of hypoglycemia.1
Transferring from Other Insulin Therapy
Sub-QFrom combination therapy of intermediate- or long-acting and short- or rapid-acting insulin: Initial dosage of insulin detemir is identical (unit-for-unit basis) to the dosage of the longer-acting insulin.1
From basal insulin only: Initial dosage of insulin detemir is identical (unit-for-unit basis) to the dosage of the basal insulin.1
Some patients with type 2 diabetes mellitus may require a higher dosage of insulin detemir than of isophane insulin human.1 4
Special Populations
Because this drug is no longer available in the U.S. market, the material in this section is no longer updated by AHFS DI. If this drug is used in countries other than the U.S., it is essential that the manufacturers’ labeling be consulted for more recently available information.
Hepatic Impairment
Dosage adjustment may be required ; carefully monitor blood glucose concentrations and adjust dosage as necessary.1 6 18 (See Hepatic Impairment under Cautions and also see Special Populations under Pharmacokinetics.)
Renal Impairment
Dosage adjustments may be required; carefully monitor blood glucose concentrations and adjust dosage as necessary.1 (See Renal Impairment under Cautions and also see Special Populations under Pharmacokinetics.)
Geriatric Patients
Conservative initial dosage, dose increments, and maintenance dosage recommended to avoid hypoglycemia.1 (See Geriatric Use under Cautions and also see Special Populations under Pharmacokinetics.)
Lactation
Dosage adjustments may be required.1 (See Specific Populations under Cautions.)
Cautions for Insulin Detemir
Contraindications
-
Because this drug is no longer available in the U.S. market, the material in this section is no longer updated by AHFS DI. If this drug is used in countries other than the U.S., it is essential that the manufacturers’ labeling be consulted for more recently available information.
-
Known hypersensitivity to insulin detemir or any ingredient in the formulation.1
Warnings/Precautions
Hypoglycemia
Most common adverse effect of insulins.1 Blood glucose concentration monitoring is recommended for all diabetic patients.1 Hypoglycemic timing may differ among various insulin formulations, and may change when the treatment regimen or timing of dosing of the insulins is changed.1 Prolonged effect of sub-Q insulin detemir may delay recovery from hypoglycemia.1
Rapid changes in serum glucose concentrations may precipitate manifestations of hypoglycemia, regardless of glucose concentrations.a h i
Use intensive insulin therapy with caution in patients with a history of hypoglycemic unawareness or recurrent, severe hypoglycemic episodes.c d e g j Higher target blood glucose concentrations (e.g., fasting blood glucose concentrations of 140 mg/dL and 2-hour postprandial concentrations of 200–250 mg/dL) are advisable in these patients.c e f
Some evidence suggests that insulin detemir may be associated with a lower risk of nocturnal hypoglycemia than isophane insulin human or insulin glargine.2 7 16 17 19 22 23
Sharing of Injection Pens
Do not share insulin detemir injection pens among patients, even if the needle has been changed; sharing poses risk for transmission of blood-borne pathogens.1
Metabolic Effects
May cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensive insulin therapy.1
Weight gain, attributable to the anabolic effect of insulin and the decrease in glucosuria, may occur with insulin therapy, including insulin detemir.1
Heart Failure
Peroxisome proliferator-activated receptor (PPAR)-γ agonists (e.g., thiazolidinediones) can cause dose-related fluid retention, particularly when used in conjunction with insulin; may lead to or exacerbate heart failure.1 32 33
Observe patients receiving insulin detemir and a PPAR-γ agonist for manifestations of heart failure (e.g., excessive/rapid weight gain, shortness of breath, edema); discontinue or reduce dose of PPAR-γ agonist if heart failure develops.1 32
Concomitant use of rosiglitazone and insulin therapy not recommended.33
Immunogenicity
Potential risk of immunogenicity.1 Insulin antibodies may increase or decrease the efficacy of insulin; dosage adjustments may be required.1 Antibody development observed in phase 3 clinical trials of insulin detemir with no apparent impact on glycemic control.1
Sensitivity Reactions
Dermatologic and Sensitivity Reactions
Lipodystrophy may occur at sites of insulin injections and may delay insulin absorption;1 7 18 rotate injection sites to reduce or prevent these effects.1 Possible localized allergic reactions (e.g., pruritus, erythema, swelling, urticaria) at injection site.1 4 12 13 14 15 Usually resolves within a few days to a few weeks; 1 14 15 but, rarely, may require discontinuance of insulin detemir.1 12 13 May be related to other factors (e.g., irritants in skin cleansing agents, poor injection technique).1 Injection site rotation within an area may reduce or prevent these effects in some patients.1 13
Generalized hypersensitivity reactions (e.g., whole-body rash, pruritus, shortness of breath, wheezing, hypotension, tachycardia, diaphoresis, anaphylaxis) reported less frequently than localized reactions, but may be life-threatening. 1
Specific Populations
Pregnancy
Category B.1
In an open-label clinical study of pregnant women with type 1 diabetes mellitus, insulin detemir therapy did not increase the risk of fetal abnormalities compared with isophane (NPH) insulin human.1 38 No difference in pregnancy outcomes or the health of the fetus and newborn with insulin detemir use.1
Studies in rats and rabbits indicate that insulin detemir and human insulin have similar embryotoxic and teratogenic effects which may be attributable to maternal hypoglycemia.1
Lactation
Not known whether insulin detemir is distributed into milk; use caution in nursing women.1 (See Lactation under Dosage and Administration.)
Pediatric Use
Safety and efficacy not established in children <2 years of age with type 1 diabetes mellitus or in pediatric patients with type 2 diabetes mellitus.1
Geriatric Use
Response in patients ≥65 years of age does not appear to differ from that in younger adults; but increased sensitivity cannot be ruled out.1 Hypoglycemia may be difficult to recognize in geriatric patients.1 (See Geriatric Patients under Dosage and Administration.)
Hepatic Impairment
Monitor blood glucose concentrations closely; dosage adjustment may be necessary.1 (See Hepatic Impairment under Dosage and Administration.)
Renal Impairment
Monitor blood glucose concentrations closely; dosage adjustment may be necessary.1 (See Renal Impairment under Dosage and Administration)
Common Adverse Effects
Hypoglycemia,1 2 3 5 11 allergic reactions,1 pruritus,1 5 rash,1 5 injection site reactions,1 5 11 lipodystrophy,1 peripheral edema,1 weight gain.1 5 11
Adults with type 1 or type 2 diabetes mellitus: Upper respiratory tract infection,1 headache,1 pharyngitis,1 influenza-like illness,1 abdominal pain,1 back pain,1 gastroenteritis,1 bronchitis.1
Pregnant women with type 1 diabetes mellitus: nasopharyngitis,1 headache,1 anemia,1 diarrhea,1 preeclampsia,1 urinary tract infection,1 gastroenteritis,1 upper abdominal pain,1 vomiting,1 spontaneous abortion,1 abdominal pain,1 oropharyngeal pain.1
Children and adolescents with type 1 diabetes mellitus: Upper respiratory tract infection,1 headache,1 pharyngitis,1 gastroenteritis,1 influenza-like illness,1 abdominal pain,1 pyrexia,1 cough,1 viral infection,1 nausea,1 rhinitis,1 vomiting.1
Drug Interactions
Because this drug is no longer available in the U.S. market, the material in this section is no longer updated by AHFS DI. If this drug is used in countries other than the U.S., it is essential that the manufacturers’ labeling be consulted for more recently available information.
Many drugs affect glucose metabolism; if such drugs are used concomitantly, may require insulin dosage adjustment and careful monitoring.1
Specific Drugs
Drugs that May Antagonize Hypoglycemic Effects |
---|
Atypical antipsychotics (e.g., olanzapine, clozapine)1 |
Danazol1 |
Estrogens or progestins (e.g., oral contraceptives)1 |
Glucagon1 |
Isoniazid1 |
Niacin26 |
Phenothiazines1 |
Protease inhibitors1 |
Somatropin1 |
Sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline)1 |
Drugs that May Have a Variable Effect on Glycemic Control |
---|
Alcohol1 |
Clonidine1 |
Lithium salts1 |
Pentamidine1 |
Drugs That may Reduce or Eliminate Signs of Hypoglycemia (Sympatholytic Agents) |
---|
β-Blockers1 |
Clonidine1 |
Guanethidine1 |
Reserpine1 |
Drug |
Interaction |
Comments |
---|---|---|
GLP-1 receptor agonists (e.g., liraglutide) |
No pharmacokinetic interaction observed following administration of single-dose sub-Q injections of insulin detemir in patients on steady-state liraglutide;1 however, risk of hypoglycemia35 |
May require dosage reduction or more conservative titration of insulin detemir1 |
PPAR-γ agonists (e.g., thiazolidinediones) |
Monitor patients for manifestations of heart failure;1 23 concomitant use of rosiglitazone not recommended24 |
|
Protein bound drugs |
Insulin Detemir Pharmacokinetics
Because this drug is no longer available in the U.S. market, the material in this section is no longer updated by AHFS DI. If this drug is used in countries other than the U.S., it is essential that the manufacturers’ labeling be consulted for more recently available information.
Absorption
Bioavailability
Following sub-Q injection, insulin detemir self-associates and binds to albumin, resulting in slow systemic absorption from injection site and a prolonged duration of action.1 2 3 5 6 7 18
Following sub-Q injection, absolute bioavailability is 60%.1
Interindividual and intraindividual variation may occur based on site of injection, tissue blood supply, temperature, and physical activity.1
Absorption occurs with less variability than with other basal insulins.2 3 7
Atrophy or hypertrophy of subcutaneous fat tissue at the injection site may affect insulin absorption.1
Duration
Dose dependent; ≤24 hours;1 37 >50% of maximum effect occurs within 3–14 hours of administration.1
Special Populations
Children 6–12 years of age: slightly increased AUC and maximum serum concentration (increased by 10 and 24%, respectively) compared with adults.1
Adolescents 13–17 years of age: No pharmacokinetic differences compared with adults.1
In geriatric patients, increased AUC.1 (See Special Populations under Elimination.)
In severe hepatic dysfunction in nondiabetics, decreased AUC.1 (See Special Populations under Dosage and Administration and also see Hepatic Impairment under Cautions.)
Distribution
Extent
Not known whether insulin detemir is distributed into milk.1
Plasma Protein Binding
>98% (albumin).1
Elimination
Half-life
Terminal half-life: Dose dependent; 5–7 hours.1
Special Populations
In geriatric patients, clearance is decreased.1 (See Special Populations under Absorption.)
In renal impairment, no difference in pharmacokinetic parameters.1 However, clearance of human insulin is decreased in renally impaired patients.1 (See Special Populations under Dosage and Administration and see Renal Impairment under Cautions.)
Stability
Because this drug is no longer available in the U.S. market, the material in this section is no longer updated by AHFS DI. If this drug is used in countries other than the U.S., it is essential that the manufacturers’ labeling be consulted for more recently available information.
Storage
Parenteral
Injection
Unopened vials, and FlexTouch injection pens: 2–8°C; store in carton to protect from light.1 Do not store directly adjacent to refrigerator cooling element and do not freeze; discard if freezing occurs.1 May keep at <30°C for ≤42 days.1
Opened (in-use) vials: 2 to <30°C for ≤42 days.1 Protect from direct heat and light.1
Opened (in-use) FlexTouch injection pens: <30°C for ≤42 days.1 Do not refrigerate; do not store with needle in place.1 Protect from direct heat and sunlight.1
Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions.
Do not mix with any other insulin or solutions.1 6 7 17 18
Actions
Because this drug is no longer available in the U.S. market, the material in this section is no longer updated by AHFS DI. If this drug is used in countries other than the U.S., it is essential that the manufacturers’ labeling be consulted for more recently available information.
-
Regulates glucose metabolism.1
-
Binds insulin receptors to lower blood glucose by increasing cellular uptake of glucose into skeletal muscle and fat; inhibits hepatic glucose production, lipolysis and proteolysis and increases protein synthesis.1
-
Longer duration of action and less intrapatient variability in blood glucose concentrations than with isophane insulin human.1 2 4 5 7 9 11
Advice to Patients
Because this drug is no longer available in the U.S. market, the material in this section is no longer updated by AHFS DI. If this drug is used in countries other than the U.S., it is essential that the manufacturers’ labeling be consulted for more recently available information.
-
Provide copy of manufacturer’s patient information.1
-
Importance of informing patients that they should never share an insulin detemir injection pen with another person, even if needle is changed; sharing of pen may pose a risk of transmission of infection.1
-
Importance of informing patients that changes to insulin regimens should be made cautiously and only under medical supervision.1
-
Advise patients of the potential adverse effects of insulin therapy (e.g., hypoglycemia, weight gain, lipodystrophy [and the need to rotate injection sites], allergic reactions).1
-
Inform patients that the ability to concentrate and react may be impaired as a result of hypoglycemia, which may pose a risk in situations where these abilities are especially important (e.g., driving, operating machinery).1 Advise patients who experience frequent hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating machinery.1
-
Inform patients to always check the label on insulin vial or injection pen prior to each injection; medication errors involving confusion between insulin detemir and other insulins (e.g., short-acting insulins) have occurred.1
-
Provide instructions regarding self-monitoring of blood glucose concentrations, injection technique, and management of hypoglycemia or hyperglycemia.1
-
Importance of not mixing insulin detemir with other insulins or solutions.1 Importance of using insulin detemir only if solution is clear and colorless with no visible particles.1
-
Discuss potential for alterations in insulin requirements in special situations (e.g., illness, emotional disturbances, other stresses).1 Discuss potential for alterations in insulin requirements as a result of inadequate or skipped doses, inadvertent administration of an incorrect dose, inadequate food intake, or skipped meals.1
-
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1
-
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
-
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Parenteral |
Injection, for subcutaneous use |
100 units/mL |
Levemir (available as FlexTouch prefilled pens and 10-mL vials) |
Novo Nordisk |
AHFS DI Essentials™. © Copyright 2024, Selected Revisions May 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
1. Novo Nordisk. Levemir (insulin detemir) injection prescribing information. Plainsboro, NJ; 2015 Feb.
2. Russell-Jones D, Simpson R, Hylleberg B et al. Effects of QD insulin detemir or neutral protamine hagedorn on blood glucose control in patients with type 1 diabetes mellitus using a basal-bolus regimen. Clin Ther. 2004; 26:724-36.
3. Home P, Bartley P, Russell-Jones D et al. Insulin detemir offers improved glycemic control compared with NPH insulin in people with type 1 diabetes. Diabetes Care. 2004; 27:1081-7. http://www.ncbi.nlm.nih.gov/pubmed/15111525?dopt=AbstractPlus
4. Misbin RI. Insulin detemir injection, Levemir: Medical review, FDA approval package. NDA number: 21-536. Rockville, MD: US Food and Drug Administration; 2005 Jun 16. (IDIS 453559)
5. Raslova K, Bogoev M, Raz I et al. Insulin detemir and insulin aspart: a promising basal-bolus regimen for type 2 diabetes. Diabetes Res Clin Pract. 2004; 66:193-201. http://www.ncbi.nlm.nih.gov/pubmed/15533587?dopt=AbstractPlus
6. Wei X. Insulin detemir injection, Levemir. Clinical pharmacology and biopharmaceutics review, FDA approval package. NDA number: 21-536. Rockville, MD: US Food and Drug Administration; 2005 Jun 16.
7. Chapman TM, Perry CM. Insulin detemir: a review of its use in the management of type 1 and 2 diabetes mellitus. Drugs. 2004; 64:2577-95. http://www.ncbi.nlm.nih.gov/pubmed/15516157?dopt=AbstractPlus
8. Novo Nordisk. Levemir FlexTouch Pen: Instructions for use. Plainsboro, NJ; 2015 Feb.
9. Plank J, Bedenlenz M, Sinner F et al. A double-blind, randomized, dose-response study investigating the pharmacodynamic and pharmacokinetic properties of the long-acting insulin analog detemir. Diabetes Care. 2005; 28:1107-1112. http://www.ncbi.nlm.nih.gov/pubmed/15855574?dopt=AbstractPlus
10. Robertson K, Schoenle E, Gucev Z et al. Insulin detemir compared with NPH insuln in children and adolescents with type 1 diabetes. Diabet Med. 2007; 24:27-34. http://www.ncbi.nlm.nih.gov/pubmed/17227321?dopt=AbstractPlus
11. Hernamsen K, Davies M, Derezinski T et al. A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetes Care. 2006; 29:1269-74. http://www.ncbi.nlm.nih.gov/pubmed/16732007?dopt=AbstractPlus
12. Darmon P, Castera V, Koeppel MC et al. Type III allergy to insulin detemir. Diabetes Care. 2005; 28:2980. Letter. http://www.ncbi.nlm.nih.gov/pubmed/16306568?dopt=AbstractPlus
13. Blumer I. Severe injection site reaction to insulin detemir. Diabetes Care. 2006; 29:946. Letter. http://www.ncbi.nlm.nih.gov/pubmed/16567849?dopt=AbstractPlus
14. Stechemesser L, Hofmann M, Hawranek T et al. Type III allergy to insulin detemir. Diabetes Care. 2006; 29:2758. Letter. http://www.ncbi.nlm.nih.gov/pubmed/17130222?dopt=AbstractPlus
15. Sola-Gazagnes A, Pecquet C, M’Bemba J et al. Type I and type IV allergy to the insulin analogue detemir. Lancet. 2007; 369:637-8. Letter.
16. Jones MC, Patel M. Insulin detemir: a long-acting insulin product. AJHP. 2006; 63(Dec 15):2466-72. http://www.ncbi.nlm.nih.gov/pubmed/17158694?dopt=AbstractPlus
17. Reviewers’ comments (personal observations).
18. Novo Nordisk, Princeton, NJ: Personal communication.
19. Pieber TR, Treichel HC, Hompesch B et al. Comparison of insulin detemir and insulin glargine in subjects with type 1 diabetes using intensive insulin therapy. Diabet Med. 2007; 24:635-42. http://www.ncbi.nlm.nih.gov/pubmed/17381500?dopt=AbstractPlus
20. Kitabchi AE, Umpierrez GE, Murphy MB et al. Hyperglycemic crises in adult patients with diabetes mellitus: a consensus statement from the American Diabetes Association. Diabetes Care. 2006; 29:2739-48. http://www.ncbi.nlm.nih.gov/pubmed/17130218?dopt=AbstractPlus
21. Philis-Tsimikas A, Charpentier G, Clauson P et al. Comparison of once-daily insulin detemir with NPH insulin added to a regimen of oral antidiabetic drugs in poorly controlled type 2 diabetes mellitus. Clin Ther. 2006; 28:1569-81.
22. Vague P, Selam JL, Skeie S et al. Insulin detemir is associated with more preducatable glycemic control and reduced risk of hypoglycemia than NPH insulin in patients with type 1 diabetes on a basal-blous regimen with premeal insulin aspart. Diabetes Car. 2003; 26:590-6.
23. Kolendorf K, Ross GP, Pavlic-Renart I et al. Insulin detemir lowers the risk of hypoglycemia and provides more consistent plasma glucose levels compared with NPH insulin in type 1 diabetes. Diabet Med. 2006; 23:729-35. http://www.ncbi.nlm.nih.gov/pubmed/16842476?dopt=AbstractPlus
24. Heise T, Nosek L, Ronn BB et al. Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes. Diabetes. 2004; 53:1614-20. http://www.ncbi.nlm.nih.gov/pubmed/15161770?dopt=AbstractPlus
25. Bartley PC, Boroev M, Larsen J et al. Superior glycaemic control, less nocturnal hypoglycemia and less weight gain with insulin detemir relative to NPH insulin in subjects with T1DM treated for 24 months using a treat-to-target concept. Paper presented at the 43rd EASD annual meeting. Amsterdam: 2007 September 17–21. Abstract 222.
26. Abbott. Niaspan (niacin extended-release tablets) prescribing information. North Chicago, IL; 2007 Sep.
30. Thalange N, Bereket A, Larsen J et al. Insulin analogues in children with Type 1 diabetes: a 52-week randomized clinical trial. Diabet Med. 2013; 30:216-25. http://www.ncbi.nlm.nih.gov/pubmed/23094597?dopt=AbstractPlus
31. DeVries JH, Bain SC, Rodbard HW et al. Sequential intensification of metformin treatment in type 2 diabetes with liraglutide followed by randomized addition of basal insulin prompted by A1C targets. Diabetes Care. 2012; 35:1446-54. http://www.ncbi.nlm.nih.gov/pubmed/22584132?dopt=AbstractPlus
32. Takeda Pharmaceuticals America, Inc. Actos (pioglitazone) tablets prescribing information. Deerfield, IL; 2013 Nov.
33. GlaxoSmithKline. Avandia (rosiglitazone maleate) tablets prescribing information. Research Triangle Park, NC; 2014 May.
34. Keating GM. Insulin detemir: a review of its use in the management of diabetes mellitus. Drugs. 2012; 72:2255-87. http://www.ncbi.nlm.nih.gov/pubmed/23110609?dopt=AbstractPlus
35. Morrow L, Hompesch M, Guthrie H et al. Co-administration of liraglutide with insulin detemir demonstrates additive pharmacodynamic effects with no pharmacokinetic interaction. Diabetes Obes Metab. 2011; 13:75-80. http://www.ncbi.nlm.nih.gov/pubmed/21114606?dopt=AbstractPlus
36. Thalange N, Bereket A, Larsen J et al. Treatment with insulin detemir or NPH insulin in children aged 2-5 yr with type 1 diabetes mellitus. Pediatr Diabetes. 2011; 12:632-41. http://www.ncbi.nlm.nih.gov/pubmed/21418455?dopt=AbstractPlus
37. Morales J. Defining the role of insulin detemir in Basal insulin therapy. Drugs. 2007; 67:2557-84. http://www.ncbi.nlm.nih.gov/pubmed/18034591?dopt=AbstractPlus
38. Hod M, Mathiesen ER, Jovanovic L et al. A randomized trial comparing perinatal outcomes using insulin detemir or neutral protamine Hagedorn in type 1 diabetes. J Matern Fetal Neonatal Med. 2014; 27:7-13. http://www.ncbi.nlm.nih.gov/pubmed/23617228?dopt=AbstractPlus
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