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Insulin Human (Monograph)

Brand names: HumuLIN N, HumuLIN R, NovoLIN N, NovoLIN R
Drug class: Short-acting Insulins

Introduction

Antidiabetic agent; a biosynthetic protein that is structurally identical to endogenous insulin secreted by the beta cells of the human pancreas.1 2 3 5 6 38 53 65 71 75 76 Commercially available as short-acting or intermediate-acting insulins.1 2 3 5 6 38 53 65 71 75 76

Uses for Insulin Human

Diabetes Mellitus

Replacement therapy for the management of diabetes mellitus.5 6 7 8 12 113 Human insulin manufactured using recombinant DNA technology has replaced insulins of animal origin (no longer commercially available in the US).103

Insulin is required in all patients with type 1 diabetes mellitus, and mandatory in the treatment of diabetic ketoacidosis and hyperosmolar hyperglycemic states.iii

Also used in patients with type 2 diabetes mellitus when weight reduction, proper dietary regulation, and/or oral antidiabetic agents have failed to maintain satisfactory glycemic control in both the fasting and postprandial state.z aa ee eee

Diet should be emphasized as the primary form of treatment when initiating therapy for patients with type 2 diabetes mellitus who do not have severe symptoms;ggg hhh caloric restriction and weight reduction are essential in obese patients.ggg

The American Diabetes Association (ADA) and many clinicians recommend the use of physiologically based, intensive insulin regimens (i.e., 3 or more insulin injections daily with dosage adjusted according to the results of multiple daily blood glucose determinations [e.g., at least 4 times daily], dietary intake, and anticipated exercise) in most type 1 and type 2 diabetic patients who are able to understand and carry out the treatment regimen, are not at increased risk for hypoglycemic episodes, and do not have other characteristics that increase risk or decrease benefit (e.g., advanced age, end-stage renal failure, advanced cardiovascular or cerebrovascular disease, other coexisting diseases that shorten life expectancy).v eee

Goals of insulin therapy in all patients generally should include maintenance of blood glucose as close as possible to euglycemia without undue risk of hypoglycemia; avoidance of symptoms attributable to hyperglycemia, glycosuria, or ketonuria; and maintenance of ideal body weight and of normal growth and development in children.bb hh

Diabetic Ketoacidosis or Hyperosmolar Hyperglycemic States

Used in the emergency treatment of diabetic ketoacidosis or hyperosmolar hyperglycemic states when rapid control of hyperglycemia is required.5 6 7 8 12 113 Regular insulin (e.g., insulin human [regular], insulin [regular]) is the insulin of choice in the treatment of such emergency conditions because of its relatively rapid onset of action and because it can be administered IV.113

Acute Stroke

Insulin injection (e.g., insulin human) also has been used IV in combination with IV potassium chloride and dextrose (i.e., GIK therapy) in a limited number of patients with acute stroke† [off-label] and mild to moderate hyperglycemia.jjj kkk

Critical Illness

Has been used to reduce morbidity and mortality in patients with critical illness† [off-label] requiring intensive care.

Gestational Diabetes Mellitus

The ADA states that human insulin is preferred for use in pregnant women or women considering pregnancy.103 The ADA recommends that insulin therapy (using insulin human) be considered in patients with gestational diabetes who, despite dietary management, have fasting plasma glucose concentrations exceeding 105 mg/dL or 2-hour postprandial plasma glucose concentrations exceeding 130 mg/dL.

Insulin Human Dosage and Administration

General

Transferring from Therapy with Other Insulins

Administration

Insulin human (regular) and isophane insulin human suspension usually are administered sub-Q.12 54 55 71 75 82 84 88

Also may administer insulin human (regular) IM† [off-label] or IV under medical supervision with close monitoring of blood glucose and potassium concentrations to avoid hypoglycemia or hypokalemia.125 Insulin human (regular) is the only form of insulin human that may be administered IV.54 55

Do not administer isophane insulin human suspension IV.54 55

Sub-Q Administration

Administer insulin human (regular) injection and isophane insulin human suspension usually by sub-Q injection.12 55 71 75 82 84 88

Avoid excessive agitation of the vial prior to withdrawing the insulin human regular dose since loss of potency, clumping, frosting, or precipitation may occur.67 101

Since suspensions contain insulin in the precipitate, gently agitate the vial to assure a homogeneous mixture for accurate measurement of each dose.6 8 75 84 92 93 Slowly rotate and invert or carefully shake the vial several times before withdrawal of each dose.6 8 75 84 Avoid vigorous shaking since frothing may interfere with correct measurement of a dose.6 8

Administer into the thighs, upper arms, buttocks, or abdomen using a 25- to 28-gauge needle, one-half to five-eighths inch in length.e g h j

Most individuals should grasp a fold of skin lightly with the fingers at least 3 inches apart and insert the needle at a 90° angle; thin individuals or children may need to pinch the skin and inject at a 45° angle to avoid IM injection, especially in the thigh area.s

Routine aspiration to check for inadvertent intravascular injection generally is not necessary.s

Inject over a period of 2–4 seconds.g h j Slow sub-Q injection of insulin suspensions may result in clogging of the tip of the needle.6 8

Press injection site lightly for a few seconds after the needle is withdrawn; do not rub.e g h j

Rotate sites so that any one site is not injected more than once every 1–2 weeks.eee

IV Administration

Dilution

For IV infusion, usually dilute insulin human (regular) injection to a concentration of 0.05–1 unit/mL in 0.9% sodium chloride or 5 or 10% dextrose injection with 40 mEq/L of potassium chloride in polypropylene infusion bags.54 55 125

Standardize 4 Safety

Standardized concentrations for insulin (regular) have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care.249 250 Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label.249 250 For additional information on S4S (including updates that may be available), see [Web]249 250 .

DKA protocols may require units/kg/hour

Table 1: Standardize 4 Safety Continuous IV Infusion Standard Concentrations for Insulin (Regular)249250

Patient Population

Concentration Standards

Dosing Units

Adults

1 unit/mL

units/hour

Pediatric patients (<50 kg)

0.2 units/mL

units/kg/hour

1 unit/mL

Dosage

Dosage must be individualized.o

Patients receiving insulin should be monitored with regular laboratory evaluations, including blood glucose determinations and glycosylated hemoglobin (hemoglobin A1c [HbA1c]) concentrations, to determine the minimum effective dosage of insulin when used alone, with other insulins, or in combination with an oral antidiabetic agent.t ii

Pediatric Patients

Diabetes Mellitus
Sub-Q

Children with newly diagnosed type 1 diabetes mellitus initially require total daily insulin dosage of 0.5–1 units/kg; requirement may be much lower during partial remission period.mmm nnn May need substantially higher daily dosage in severe insulin resistance (e.g., puberty, obesity).125

In patients with type 2 diabetes mellitus, initial total daily dosage ranges from 0.2–0.4 units/kg.125

Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic States
IV

In children and adolescents <20 years of age, the ADA recommends initially an IV infusion of regular insulin at a rate of 0.1 units/kg per hour.113 An initial direct IV injection of regular insulin is not recommended in such patients.113

IM† [off-label], then Sub-Q

If IV access is unavailable, regular insulin may be given IM in an initial dose of 0.1 units/kg, followed by 0.1 units/kg per hour sub-Q or IM until acidosis is resolved (i.e., venous pH >7.3, serum bicarbonate concentration >15 mEq/L).113

Dosage Following Resolution of Diabetic Ketoacidosis
IV, then Sub-Q

Upon resolution of ketoacidosis or the hyperosmolar state, the regular insulin IV infusion rate should be decreased to 0.05 units/kg per hour until sub-Q replacement insulin therapy is initiated.113

Initiate replacement therapy at an insulin dosage of 0.5–1 units/kg daily given sub-Q in divided doses ((2/3) of the daily dosage in the morning [(1/3) as short-acting insulin, (2/3) as intermediate-acting insulin] and (1/3) in the evening [½ as short-acting insulin, ½ as intermediate-acting insulin]).113 In pediatric patients with newly diagnosed diabetes mellitus, may administer 0.1–0.25 units/kg of regular insulin every 6–8 hours during the first 24 hours to determine insulin requirements.113

Adults

Diabetes Mellitus
Sub-Q

Initial total daily insulin dosages in adults with type 1 diabetes mellitus range from 0.2–1 units/kg.v ee ff eee lll mmm May need substantially higher daily dosage in severe insulin resistance (e.g., obesity).125

In patients with type 2 diabetes mellitus, initial total daily dosage ranges from 0.2–0.4 units/kg.125

Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic States
Mild Diabetic Ketoacidosis
IV, then Sub-Q or IM† [off-label]

For the treatment of mild diabetic ketoacidosis (plasma glucose >250 mg/dL with an arterial pH of 7.25–7.3 and serum bicarbonate of 15–18 mEq/L), the ADA recommends a loading dose of 0.4–0.6 units/kg of regular insulin administered in 2 doses, with 50% given by direct IV injection and 50% by sub-Q or IM injection.113 After the loading dose, administer 0.1 units/kg per hour of regular insulin sub-Q or IM.113

Moderate to Severe Diabetic Ketoacidosis
IV

For the treatment of moderate to severe diabetic ketoacidosis (plasma glucose >250 mg/dL with arterial pH ≤7–7.24 and serum bicarbonate ≤10–15 mEq/L) or hyperosmolar hyperglycemia in adults, the ADA recommends a loading dose of 0.15 units/kg of regular insulin by direct IV injection, followed by continuous IV infusion of 0.1 units/kg per hour.113

If plasma glucose concentrations do not fall by 50 mg/dL within the first hour of insulin therapy, insulin infusion rate may be doubled every hour, provided the patient is adequately hydrated, until plasma glucose decreases steadily by 50–75 mg/dL per hour.113

When a plasma glucose concentration of 250 or 300 mg/dL is achieved in patients with diabetic ketoacidosis or hyperosmolar hyperglycemia, respectively, may decrease the insulin infusion rate to 0.05–0.1 units/kg per hour.113 May need to adjust the rate of insulin administration or the concentration of dextrose to maintain glucose concentration until resolution of diabetic ketoacidosis (i.e., serum glucose <200 mg/dL, venous pH >7.3, serum bicarbonate ≥18 mEq/L) or hyperosmolar hyperglycemia (i.e., patient mentally alert, serum osmolality of ≤315 mOsm/kg).b

Dosage Following Resolution of Diabetic Ketoacidosis
IV, then Sub-Q

Upon resolution of diabetic ketoacidosis (i.e., plasma glucose <200 mg/dL, venous pH >7.3, serum bicarbonate ≥18 mEq/L) or hyperosmolar hyperglycemia in patients who are unable to eat, continue IV insulin and fluid replacement; may give sub-Q regular insulin as needed every 4 hours.113 May give regular insulin sub-Q in 5-unit increments for every 50-mg/dL increase in blood glucose concentrations above 150 mg/dL, to a dose of up to 20 units of regular insulin for a blood glucose of ≥300 mg/dL.113

When the patient is able to eat, initiate a multiple-dose, sub-Q insulin regimen consisting of a short- or rapid-acting insulin and an intermediate- or long-acting insulin.113 Continue regular insulin IV for 1–2 hours after initiation of the sub-Q insulin regimen to ensure adequate plasma insulin concentrations during the transition.113 Abrupt discontinuance of IV insulin with the institution of delayed-onset sub-Q insulin may lead to worsened glycemic control.113 Patients with known diabetes mellitus may reinstitute the insulin regimen they were receiving before the onset of hyperglycemic crises, and the regimen may be adjusted further as needed for adequate glycemic control.113

Patients with newly diagnosed diabetes mellitus should receive a total daily insulin dosage of 0.5–1 units/kg as part of a multiple-dose regimen of insulin, until an optimal dosage is established.113 May manage some patients with newly diagnosed type 2 diabetes mellitus with diet therapy and oral antidiabetic agents following resolution of hyperglycemic crises.113

Cautions for Insulin Human

Warnings/Precautions

Warnings

Hypoglycemia

Care should be taken in patients who are most at risk for the development of these effects, including patients who are fasting or those with defective counterregulatory responses (e.g., patients with autonomic neuropathy, adrenal or pituitary insufficiency, those receiving β-adrenergic blocking agents).v z ee ff r ss bbb .

Reduce the potential for late postprandial hypoglycemia by altering the timing, frequency, and content of meals; altering exercise patterns; frequently monitoring blood glucose concentrations; adjusting insulin dosage; and/or switching to a more rapid-acting insulin (i.e., insulin lispro).v x y aa ff gg hh jj kk mm nn qq uu vv ww xx eee

Use intensive insulin therapy with caution in patients with a history of hypoglycemic unawareness or recurrent, severe hypoglycemic episodes.v cc ee hh tt ccc 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.v ee ff

Exercise extreme caution when concentrated (U-500) insulin human (regular) injection is used in patients with marked insulin resistance (i.e., daily insulin requirements >200 units).o Inadvertent overdosage may result in irreversible insulin shock.o Serious consequences may result if this concentrated injection is used without constant medical supervision.o

Sensitivity Reactions

Local reactions (e.g., pain at injection site, erythema, pruritus, swelling) reported.c Warming refrigerated insulin to room temperature prior to use will limit local irritation at the injection site.67 101

Generalized hypersensitivity reactions (e.g., rash, shortness of breath, wheezing, hypotension, tachycardia, diaphoresis) reported less frequently, but may be life-threatening.c The incidence of allergic reactions may have decreased with the availability of more purified insulin (e.g., insulin human, insulin lispro).z aa ff

Insulin Resistance

Chronic insulin resistance resulting from immunity has been decreased by changing to a purified insulin preparation (e.g., insulin human).qq zz aaa

General Precautions

Lipodystrophy

Atrophy or hypertrophy of subcutaneous fat tissue may occur at sites of frequent insulin injections.c Rotate injection site to reduce or prevent these effects.d

Hypokalemia

Care should be taken in patients who are most at risk for the development of hypokalemia, such as those who are receiving potassium-lowering drugs.t ff

Since diabetic ketoacidosis often is associated with hypokalemia, the possibility of potassium imbalance should be evaluated and, if present, corrected before administration of insulin as long as adequate renal function is assured.

Concurrent Illness

Illness, particularly nausea and vomiting, and changes in eating patterns may alter insulin requirements.c

Use of Fixed Combinations

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category B.

Most clinicians recommend initiation of intensive insulin therapy (3 or more insulin injections daily with dosage adjusted according to results of at least 4 daily blood glucose determinations, dietary intake, and anticipated exercise) prior to conception in diabetic patients who are well controlled on oral hypoglycemic agents and who are considering pregnancy.aa eee

Geriatric Use

The safety of an intensive insulin regimen (3 or more insulin injections daily with dosage adjusted according to results of at least 4 daily blood glucose determinations, dietary intake, and anticipated exercise) in geriatric patients has been questioned.ff hh ii oo ddd eee Increased incidence of hypoglycemia associated with intensive insulin therapy may increase the probability of strokes and heart attacks in such patients.ff hh ii oo ddd eee

Hypoglycemic reactions in geriatric diabetic patients may mimic a cerebrovascular accident.d An increased incidence of macrovascular disease in geriatric patients with type 2 diabetes mellitus may make such patients more vulnerable to serious consequences of hypoglycemiahh (e.g., fainting, seizures, falls, stroke, silent ischemia, MI, sudden death).hh

Common Adverse Effects

Hypoglycemia.s t ff pp

Drug Interactions

Specific Drugs

Insulin Human Pharmacokinetics

Absorption

Bioavailability

Because of its protein nature, insulin is destroyed in the GI tract and usually is administered parenterally.e

Following sub-Q injection, insulin human (regular) appears to be absorbed more rapidly than purified pork insulin (regular) (no longer commercially available in the US).17 24 28 29 30 42

Following IM or IV administration, serum insulin concentrations are similar for insulin human (regular) and purified pork insulin (regular) (no longer commercially available in the US).17 18 19 31 32 43

Onset and Duration of Action of Human Insulins

In patients with diabetes mellitus, insulin human appears to have a slightly faster onset and shorter duration of action than purified pork insulin (no longer commercially available in the US).58

Distribution

Extent

Rapidly distributed throughout extracellular fluids.e

Elimination

Metabolism

Rapidly metabolized mainly in the liver and to a lesser extent in the kidneys and muscle tissue.e

Elimination Route

Excreted in the urine principally as metabolites.e

Half-life

Insulin has a plasma half-life of a few minutes in healthy individuals.e The biologic half-life may be prolonged in diabetic patients, probably as a result of binding of the hormone to antibodies.w eee

Special Populations

In patients with renal impairment, the biologic half-life may be prolonged as a result of altered degradation/decreased clearance.w eee

Stability

Storage

Parenteral

Solution for Injection

With unopened vials or cartridges of insulin human injections than have not been placed in a delivery device, store at 2–8°C; do not freeze.5 7 53 64 67 71 82 89 93 100 101 c j Vials in use, store below 30°C; protect from excessive heat or cold and light.67 c

Discard insulin human (regular) injection exhibiting discoloration, turbidity, or unusual viscosity,5 7 71 82 88 89 since these changes indicate deterioration or contamination.5 7 101

Suspension for Injection

With unopened vials, pens, prefilled syringes, or cartridges containing isophane insulin human suspensions, 2–8°C in the original container; do not freeze.6 8 53 64 65 80 84 92 93 100 101 f g h i k l m p q With vials in use, below 30°C; protect from heat and light.80 g h i k l m r Freezing will cause isophane insulin human to resuspend improperly, preventing accurate measurement of a dose.54 55 In addition, agglomeration of particles may occur, altering absorption from the injection site.54 55

Preparations of insulin isophane suspension available with a delivery device (e.g., Humulin N pen) are stable below 30°C for 14 days.67 m Protect from excessive heatf m or coldf and light.f m

Combination preparations of insulin human and isophane insulin human suspension available with a delivery device (Humulin 70/30 pen) are stable below 30°C for 10 days.67 p Should discard unrefrigerated insulin after 10 days.p Protect from excessive heat and light.p

Should discard isophane insulin human if the suspension is clear, if it remains clear after the vial is rotated, if the precipitate has become clumped or granular in appearance, or if solid particles have adhered to the wall of the vial.6 8 64 65 75 76 80 83 84 90 92 93 101

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.

Insulin Human (Regular) (Recombinant DNA Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

100 units/mL

HumuLIN R

Lilly

NovoLIN R

Novo Nordisk

500 units/mL

HumuLIN R (concentrated U-500)

Lilly
Isophane Insulin Human (Recombinant DNA Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Suspension, sterile

100 units/mL

HumuLIN N

Lilly

HumuLIN N Pen (available as prefilled cartridge preassembled into pen)

Lilly

NovoLIN N

Novo Nordisk
Insulin Human Combinations (Recombinant DNA Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Suspension, sterile

Insulin Human (Regular) 30 units/mL with Isophane Insulin Human 70 units/mL

HumuLIN 70/30

Lilly

HumuLIN 70/30 Pen (available as cartridge pressambled into pen)

Lilly

NovoLIN 70/30

Novo Nordisk

AHFS DI Essentials™. © Copyright 2024, Selected Revisions June 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. Chance RE, Kroeff EP, Hoffman BH. Chemical, physical and biological properties of biosynthetic human insulin. Diabetes Care. 1981; 4:147-55. http://www.ncbi.nlm.nih.gov/pubmed/7011716?dopt=AbstractPlus

2. Markussen J, Jorgensen K, Kim L et al. Human monocomponent insulin: chemistry and characteristics of human insulin (Novo). Diabetologia. 1981; 21:302.

3. Markussen J, Damgaard U, Pingel M et al. Human insulin (Novo): chemistry and characteristics. Diabetes Care. 1981; 6(Suppl 1):4-8.

4. Markussen J. The advent of human insulin in diabetes therapy. Medicographia. 1982; 4:39-44.

5. Eli Lilly and Company. Humulin R injection prescribing information. Indianapolis, IN; 1983 Jun.

6. Eli Lilly and Company. Humulin N sterile suspension prescribing information. Indianapolis, IN; 1987 Feb.

7. Squibb-Novo, Inc. Actrapid Human injection (Regular) prescribing information. Princeton, NJ; 1983 Jul.

8. Squibb-Novo, Inc. Monotard Human Zinc suspension (Lente) prescribing information. Princeton, NJ; 1983 Jul.

9. Larner J. Insulin and oral hypoglycemic drugs; glucagon. In: Gilman AG, Goodman L, Gilman A, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 6th ed. New York: Macmillan Publishing Company; 1980:1497-1523.

10. Anon. Squibb-Novo human insulins. Squibb-Novo, Inc, Princeton, NJ. Publication no 393-019; 1983 Jul.

11. Newton DW. Introduction: physicochemical determinants of incompatibility and instability of drugs for injection and infusion. In: Trissel LA. Handbook on Injectable Drugs. Bethesda, MD: American Society of Health-System Pharmacists.

12. Squibb-Novo, Inc. Insulin monograph. Actrapid Human, Monotard Human. Princeton, NJ; 1983 Sep.

13. Adeniyi-Jones ROC, Jones RH, Barnes DG et al. Porcine and human insulin (Novo): a comparison of their metabolism and hypoglycemic activity in normal man. Diabetes Care. 1983; 6(Suppl 1):9-12. http://www.ncbi.nlm.nih.gov/pubmed/6343043?dopt=AbstractPlus

14. Crea R, Kraszewski A, Hirose T et al. Chemical synthesis of genes for human insulin. Proc Natl Acad Sci USA. 1978; 75:5765-9. http://www.ncbi.nlm.nih.gov/pubmed/282602?dopt=AbstractPlus

15. Goeddel DV, Kleid DG, Bolivar F et al. Expression in Escherichia coli of chemically synthesized genes for human insulin. Proc Natl Acad Sci USA. 1979; 76:106-10. http://www.ncbi.nlm.nih.gov/pubmed/85300?dopt=AbstractPlus

16. Morihara K, Oka T, Tsuzuki H. Semi-synthesis of human insulin by trypsin catalyzed replacement of Ala-B30 by Thr in porcine insulin. Nature. 1979; 280:412-3. http://www.ncbi.nlm.nih.gov/pubmed/460416?dopt=AbstractPlus

17. Ebihara A, Kondo K, Ohashi K et al. Comparative clinical pharmacology of human insulin (Novo) and porcine insulin in normal subjects. Diabetes Care. 1983; 6(Suppl 1):17-22. http://www.ncbi.nlm.nih.gov/pubmed/6343032?dopt=AbstractPlus

18. Home PD, Shepherd GAA, Noy G et al. Comparison of the activity and pharmacokinetics of porcine insulin and human insulin (Novo) as assessed by the glucose clamp technique in normal and diabetic man. Diabetes Care. 1983; 6(Suppl 1):23-8. http://www.ncbi.nlm.nih.gov/pubmed/6343033?dopt=AbstractPlus

19. Charles MA, Szekeres A, Staten M et al. Comparison of porcine insulin and human insulin (Novo) using the glucose-controlled insulin infusion system, glucose-insulin dose-response curves, and the outpatient effectiveness of human insulin (Novo) in insulin-dependent diabetes. Diabetes Care. 1983; 6(Suppl 1):29-34. http://www.ncbi.nlm.nih.gov/pubmed/6343034?dopt=AbstractPlus

20. Mirouze J, Benghernaout O, Pham TC et al. Comparative analysis of soluble porcine and human insulin (Novo) using the artificial pancreas. Diabetes Care. 1983; 6(Suppl 1):40-2. http://www.ncbi.nlm.nih.gov/pubmed/6343037?dopt=AbstractPlus

21. Sestoft L, Volund A, Gammeltoft S et al. The biological properties of human insulin. Acta Med Scand. 1982; 212:21-8. http://www.ncbi.nlm.nih.gov/pubmed/6751025?dopt=AbstractPlus

22. Keen H, Glynne A, Pickup JC et al. Human insulin produced by recombinant DNA technology: safety and hypoglycemic potency in healthy men. Lancet. 1980; 2:398-401. http://www.ncbi.nlm.nih.gov/pubmed/6105520?dopt=AbstractPlus

23. Clark AJL, Knight G, Wiles PG et al. Biosynthetic human insulin in the treatment of diabetes. Lancet. 1982; 2:354-7. http://www.ncbi.nlm.nih.gov/pubmed/6124760?dopt=AbstractPlus

24. Sonnenberg GE, Kemmer FW, Cuppers HJ et al. Subcutaneous use of regular human insulin (Novo): pharmacokinetics and continuous insulin infusion therapy. Diabetes Care. 1983; 6(Suppl 1):35-9. http://www.ncbi.nlm.nih.gov/pubmed/6343035?dopt=AbstractPlus

25. Owens DR, Jones MK, Hayes TM et al. Human insulin: study of safety and efficacy in man. BMJ. 1981; 282:1264-6. http://www.ncbi.nlm.nih.gov/pubmed/6784807?dopt=AbstractPlus

26. Owens ER, Jones MK, Birtwell AJ et al. The clinical pharmacology of human insulin (Novo) in normal subjects. Diabetes Care. 1983; 6(Suppl 1):13-6. http://www.ncbi.nlm.nih.gov/pubmed/6133710?dopt=AbstractPlus

27. Karam JH. Introduction: evolution of human insulin in the therapy of diabetes mellitus. Diabetes Care. 1983; 6(Suppl 1):1-2. http://www.ncbi.nlm.nih.gov/pubmed/6343030?dopt=AbstractPlus

28. Botterman P, Gyaram H, Wahl K et al. Pharmacokinetics of biosynthetic human insulin and characteristics of its effects. Diabetes Care. 1981; 4:168-9. http://www.ncbi.nlm.nih.gov/pubmed/7011719?dopt=AbstractPlus

29. Federlin K, Laube H, Velcovsky HG. Biologic and immunologic in vivo and in vitro studies with biosynthetic human insulin. Diabetes Care. 1981; 4:170-4. http://www.ncbi.nlm.nih.gov/pubmed/7011720?dopt=AbstractPlus

30. Berger M, Cuppers HJ, Chantelau EA et al. Absorption kinetics of subcutaneously injected insulin preparations. In: Skyler JS, ed. Insulin update: 1982. Princeton: Excerpta Medica; 1982:97-110.

31. Owens DR, Jones MK, Hayes TM et al. Comparative study of subcutaneous, intramuscular and intravenous administration of human insulin. Lancet. 1981; 2:118-22. http://www.ncbi.nlm.nih.gov/pubmed/6113483?dopt=AbstractPlus

32. Massi-Benedetti M, Burrin JM, Capaldo B et al. A comparative study of biosynthetic human insulin and pork insulin using the glucose clamp technique in normal subjects. Diabetes Care. 1981; 4:163-7. http://www.ncbi.nlm.nih.gov/pubmed/7011718?dopt=AbstractPlus

33. Etzwiler DD. International symposium on human insulin: a summary. Diabetes Care. 1983; 6(Suppl 1):66-8.

34. Schernthaner G, Borkenstein M, Fink M et al. Immunogenicity of human insulin (Novo) or pork monocomponent insulin in HLA-DR-typed insulin-dependent diabetic individuals. Diabetes Care. 1983; 6(Suppl 1):43-8. http://www.ncbi.nlm.nih.gov/pubmed/6343038?dopt=AbstractPlus

35. Falholt K, Hoskom JAM, Karamanos BG et al. Insulin-specific IgE in serum of 67 diabetic patients against human insulin (Novo), porcine insulin, and bovine insulin. Four case reports. Diabetes Care. 1983; 6(Suppl 1):61-5. http://www.ncbi.nlm.nih.gov/pubmed/6343042?dopt=AbstractPlus

36. Wu W, Nolte M, Hellmann N et al. Superiority of human monocomponent insulin to pork monocomponent insulin in a diabetic with severe immune insulin resistance. Clin Res. 1983; 31:95A.

37. Karam J, Brink S, Clements R et al. Evaluation of efficacy and safety of human insulin (Novo) in the treatment of insulin-dependent diabetes mellitus: a double-blind, multicenter clinical trial. Diabetes Care. 1983; 6(Suppl 1):56-60. http://www.ncbi.nlm.nih.gov/pubmed/6343041?dopt=AbstractPlus

38. Johnson IS. Authenticity and purity of human insulin (recombinant DNA). Diabetes Care. 1982; 5(Suppl 2):4-12. http://www.ncbi.nlm.nih.gov/pubmed/6765539?dopt=AbstractPlus

39. Ebihara A, Kondo K, Ohashi K et al. Clinical pharmacology of human insulin of recombinant DNA origin in healthy volunteers. Diabetes Care. 1982; 5(Suppl 2):35-8. http://www.ncbi.nlm.nih.gov/pubmed/6765537?dopt=AbstractPlus

40. Miroaze J, Monnier L, Richard JL et al. Comparative study of NPH human insulin (recombinant DNA) and pork insulin in diabetic subjects: preliminary report. Diabetes Care. 1982; 5(Suppl 2):60-2. http://www.ncbi.nlm.nih.gov/pubmed/6765543?dopt=AbstractPlus

41. Galloway JA, Root MA, Bergstrom R et al. Clinical pharmacologic studies with human insulin (recombinant DNA). Diabetes Care. 1982; 5(Suppl 2):13-22. http://www.ncbi.nlm.nih.gov/pubmed/6765524?dopt=AbstractPlus

42. Kemmer FW, Sonnenberg G, Cuppers HJ et al. Absorption kinetics of semisynthetic human insulin and biosynthetic (recombinant DNA) human insulin. Diabetes Care. 1982; 5(Suppl 2):23-8. http://www.ncbi.nlm.nih.gov/pubmed/6765535?dopt=AbstractPlus

43. Pickup JC, Bilous RW, Viberti GC et al. Plasma insulin and C-Peptide after subcutaneous and intravenous administration of human insulin (recombinant DNA) and purified porcine insulin in healthy men. Diabetes Care. 1982; 5(Suppl 2):29-34. http://www.ncbi.nlm.nih.gov/pubmed/6765536?dopt=AbstractPlus

44. Howey DC, Fineberg SE, Nolen PA. The therapeutic efficacy of human insulin (recombinant DNA) in patients with insulin-dependent diabetes mellitus: a comparative study with purified porcine insulin. Diabetes Care. 1982; 5(Suppl 2):73-7. http://www.ncbi.nlm.nih.gov/pubmed/6765546?dopt=AbstractPlus

45. Schernthaner G. Affinity of IgG-insulin antibodies to human (recombinant DNA) insulin and porcine insulin in insulin-treated diabetic individuals with and without insulin resistance. Diabetes Care. 1982; 5(Suppl 2):114-8. http://www.ncbi.nlm.nih.gov/pubmed/6765520?dopt=AbstractPlus

46. Fireman P, Fineberg SE, Galloway JA. Development of IgE antibodies to human (recombinant DNA), porcine, and bovine insulin in diabetic subjects. Diabetes Care. 1982; 5(Suppl 2):119-25. http://www.ncbi.nlm.nih.gov/pubmed/6765521?dopt=AbstractPlus

47. Clark AJ, Wiles PG, Leiper JM. A double-blind crossover trial comparing human insulin (recombinant DNA) with animal insulin in the treatment of previously insulin-treated diabetic patients. Diabetes Care. 1982; 5(Suppl 2):129-34. http://www.ncbi.nlm.nih.gov/pubmed/6765523?dopt=AbstractPlus

48. Galloway JA, Peck FB Jr, Fineberg SE. The U.S. “new patient” and “transfer” studies. Diabetes Care. 1982; 5(Suppl 2):135-9. http://www.ncbi.nlm.nih.gov/pubmed/6765525?dopt=AbstractPlus

49. Lotz N, Bachmann W, Menhert H. Human insulin (recombinant DNA) in the treatment of patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM). Diabetes Care. 1982; 5(Suppl 2):149-51. http://www.ncbi.nlm.nih.gov/pubmed/6765527?dopt=AbstractPlus

50. Maneschi F, Fineberg SE, Kohner EM. Successful treatment of immune-mediated insulin resistance by human insulin (recombinant DNA). Diabetes Care. 1982; 5(Suppl 2):175-9. http://www.ncbi.nlm.nih.gov/pubmed/6765532?dopt=AbstractPlus

51. Carveth-Johnson AO, Mylvaganam K, Child DF. Generalized allergic reaction with synthetic human insulin. Lancet. 1982; 2:1287. http://www.ncbi.nlm.nih.gov/pubmed/6128592?dopt=AbstractPlus

52. Blandford RL, Sewell H, Sharp P et al. Generalized allergic reaction with synthetic human insulin. Lancet. 1982; 2:1468.

53. The United States pharmacopeia, 21st rev, and The national formulary, 16th ed. Suppl 1. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1984:1732.

54. Welles JS (Eli Lilly and Company, Indianapolis): Personal communication; 1984 Mar 14.

55. Mellowes JR (Squibb-Novo, Inc, Princeton, NJ): Personal communication; 1984 Mar 26.

56. Reviewers’ comments (personal observations); 1984 Mar.

57. Grammer LC, Metzger BE, Patterson R. Cutaneous allergy to human (recombinant DNA) insulin. JAMA. 1984; 251:1459-60. http://www.ncbi.nlm.nih.gov/pubmed/6366262?dopt=AbstractPlus

58. Anon. Humulin human insulin (recombinant DNA origin). The natural evolution of insulin therapy. Eli Lilly and Company, Indianapolis. Publication No. 60-HI-2006-1; 1983 Jul.

59. Fineberg SE, Galloway JA, Fineberg NS et al. Immunogenicity of recombinant DNA human insulin. Diabetologia. 1983; 25:465-9. http://www.ncbi.nlm.nih.gov/pubmed/6198228?dopt=AbstractPlus

60. The United States pharmacopeia, 21st rev, and The national formulary, 16th ed. Suppl 2. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1985:1849.

61. The United States pharmacopeia, 21st rev, and The national formulary, 16th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1985:539.

62. Westby R (Eli Lilly and Company, Indianapolis): Personal communication; 1986 Feb 24.

63. Manufacturer’s comments (Novo Nordisk, Princeton, NJ): Personal communication.

64. Anon. Nordisk human insulins (semi-synthetic). Nordisk-USA, Rockville, MD. Publication No. 17066-9/86-10M; 1986 Sep.

65. Novo Nordisk. Novolin 70/30 sterile suspension prescribing information. Princeton, NJ; 1985 May.

66. Eli Lilly and Company. Humulin BR information for the patient. Indianapolis, IN; 1986 Jun.

67. Novo Nordisk, Princeton, NJ: Personal communication.

68. Squibb-Novo, Inc. NovoPen insulin delivery system. Princeton, NJ; 1987 Feb.

69. Novo Information Center. NovoPen fact sheet. New York; (undated).

70. NovoPen prescribing information. In: Huff BB, ed. Physicians’ desk reference. 42nd ed. Oradell, NJ; Medical Economics Company Inc; 1988:2076.

71. Novo Nordisk. Novolin R PenFill patient information. Princeton, NJ; 2000 Feb.

72. Russell MJ (Squibb-Novo, Inc, Princeton, NJ): Personal communication; 1988 Feb 25.

73. Squibb-Novo, Inc. NovoPen insulin delivery device patient information. Princeton, NJ; 1986 Oct.

74. Squibb-Novo, Inc. NovolinPen Dial-A-Dose insulin delivery device prescribing information. In: Huff BB, ed. Physicians’ desk reference. 43rd ed. Oradell, NJ: Medical Economics Company Inc; 1989:2110-3.

75. Novo Nordisk. Novolin N PenFill patient information. Princeton, NJ; 1991 Apr.

76. Novo Nordisk. Novolin 70/30 PenFill patient information. Princeton, NJ; 1991 Apr.

77. Frohnauer MK (Eli Lilly and Company, Indianapolis, IN): Personal communication; 1988 Dec 22.

78. Siegler DE, Reeves ML, Goldberg RB et al. Pharmacokinetics of ultralente insulin preparation. Diabetes. 1984; 33(Suppl 1):61A.

79. Reeves ML, Seigler DE, Goldberg RB et al. Pharmacokinetics of ultralente (U) insulin preparations. Diabetes. 1986; 35(Suppl 1):63A.

80. Eli Lilly and Company. Humulin U ultralente (human insulin rDNA origin) extended zinc suspension patient information. Indianapolis, IN; 2000 Aug 3.

81. Gossain VV, Rovner DR, Mohan K. Systemic allergy to human (recombinant DNA) insulin. Ann Allergy. 1985; 55:116-8. http://www.ncbi.nlm.nih.gov/pubmed/3896050?dopt=AbstractPlus

82. Novo Nordisk. Novolin R patient information. Princeton, NJ; 1991 Apr.

83. Novo Nordisk. Novolin L patient information. Princeton, NJ; 1991 Apr.

84. Novo Nordisk. Novolin N patient information. Princeton, NJ; 1991 Apr.

85. Davidson JA, Ramirez LC, Selam JL. Transfer of patients with diabetes from semisynthetic human insulin to human insulin prepared by recombinant DNA technology using baker’s yeast: a double-blind, randomized study. Clin Therap. 1991; 13:557-68.

86. Raskin P, Clements RS Jr. The use of human insulin derived from baker’s yeast by recombinant DNA technology. Clin Therap. 1991; 13:569-78.

87. Novo Nordisk. Velosulin BR fact sheet. Undated.

88. Novo Nordisk. Velosulin BR regular human insulin injection (semi-synthetic) prescribing information (dated 1995 Jan). In: Physicians’ desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:1795-6.

89. Novo Nordisk. Novolin R regular human insulin injection (recombinant DNA origin) prescribing information. In: Physicians’ desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:1795.

90. Novo Nordisk. Novolin N Penfill NPH human insulin isophane suspension injection (recombinant DNA origin) prescribing information. In: Physicians’ desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:1798.

91. Novo Nordisk. Novolin R Penfill regular human insulin injection (recombinant DNA origin) prescribing information. In: Physicians’ desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:1798.

92. Novo Nordisk. Novolin L lente human insulin zinc suspension injection (recombinant DNA origin) prescribing information. In: Physicians’ desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:1795.

93. Novo Nordisk. Novolin 70/30 NPH human insulin isophane suspension injection and regular human insulin injection (recombinant DNA origin) prescribing information. In: Physicians’ desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:1794- 5.

94. Novo Nordisk. Novolin 70/30 Penfill NPH human insulin isophane suspension injection and regular human insulin injection (recombinant DNA origin) prescribing information. In: Physicians’ desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:1797-8.

95. Ryan TJ, Antman EM, Brooks NH et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: 1999 update: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). From website. http://www.cardiosource.org/Science-And-Quality/Practice-Guidelines-and-Quality-Standards.aspx

96. Diaz R, Paolasso EA, Piegas LS et al for the ECLA (Estudios Cardiologicos Latinoamerica) Collaborative Group. Metabolic modulation of acute myocardial infarction: The ECLA Glucose-Insulin-Potassium Pilot Trial. Circulation. 1998; 98:2227-34. http://www.ncbi.nlm.nih.gov/pubmed/9867443?dopt=AbstractPlus

97. Apstein CS. Glucose-insulin-potassium for acute myocardial infarction: remarkable results from a new perspective, randomized trial. Circulation. 1998; 98:2223-6. http://www.ncbi.nlm.nih.gov/pubmed/9826307?dopt=AbstractPlus

98. Fath-Ordoubadi, Beatt KJ. Glucose-insulin-potassium therapy for treatment of acute myocardial infarction: an overview of randomized placebo-controlled trials. Circulation. 1997; 96:1152-6. http://www.ncbi.nlm.nih.gov/pubmed/9286943?dopt=AbstractPlus

99. Apstein CS. Glucose-insulin-potassium in acute myocardial infarction: the time has come for a large, prospective trial. Circulation. 1997; 96:1074-7. http://www.ncbi.nlm.nih.gov/pubmed/9286931?dopt=AbstractPlus

100. Anon. Insulin systemic. In: United States Pharmacopeia Dispensing Information (USP DI). Vol II. Advice for the patient: drug information in lay language. 19th ed. Englewood, CO: Micromedex; 1999:962-5.

101. American Diabetes Association. Clinical practice recommendations: insulin administration. Diabetes Care. 2000; 23(Suppl. 1):S86-9.

102. Novo Nordisk. Velosulin BR buffered regular human insulin injection (rDNA origin) patient information. Princeton, NJ; 1999 Jul.

103. American Diabetes Association. Insulin administration. Diabetes Care. 2002; 25(Suppl 1):S112-5.

104. Cefalu WT, Skyler JS, Kourides IA et al. Inhaled human insulin treatment in patients with type 2 diabetes mellitus. Ann Intern Med. 2001; 134:203-7. http://www.ncbi.nlm.nih.gov/pubmed/11177333?dopt=AbstractPlus

105. Skyler JS, Cefalu WT, Kourides IA et al. Efficacy of inhaled human insulin in type 1 diabetes mellitus: a randomised proof-of-concept study. Lancet. 2001; 357:331-5. http://www.ncbi.nlm.nih.gov/pubmed/11210993?dopt=AbstractPlus

106. Gale EAM. Two cheers for inhaled insulin. Lancet. 2001; 357:324-5. http://www.ncbi.nlm.nih.gov/pubmed/11210986?dopt=AbstractPlus

107. Nathan DM. Inhaled insulin for type 2 diabetes: Solution or distraction? Ann Intern Med. 2001; 134:242-4. Editorial.

108. Laube BL, Benedict GW, Dobs AS. The lung as an alternative route of delivery for insulin in controlling postprandial glucose levels in patients with diabetes. Chest. 1998; 114:1734-9. http://www.ncbi.nlm.nih.gov/pubmed/9872209?dopt=AbstractPlus

109. Heinemann L, Traut T, Heise T. Time-action profile of inhaled insulin. Diabetic Med. 1997; 14:63-72. http://www.ncbi.nlm.nih.gov/pubmed/9017356?dopt=AbstractPlus

110. Laube BL, Georgopoulos A, Adams III GK. Preliminary study of the efficacy of insulin aerosol delivered by oral inhalation in diabetic patients. JAMA. 1993; 269:2106-9. http://www.ncbi.nlm.nih.gov/pubmed/8385716?dopt=AbstractPlus

111. Novo Nordisk Pharmaceuticals, Inc. NovoPen Junior instruction manual. Princeton, NJ; 2002.

112. Van Den Berghe G, Wouters P, Weekers F et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001; 345:1359-67. http://www.ncbi.nlm.nih.gov/pubmed/11794168?dopt=AbstractPlus

113. American Diabetes Association. Hyperglycemic crises in patients with diabetes mellitus. Diabetes Care. 2002; 25(Suppl. 1):S100-8.

125. Novo Nordisk. Novolin R (insulin human regular) injection prescribing information. Princeton, NJ; 2005 Oct.

249. ASHP. Standardize 4 Safety: pediatric continuous infusion standard. Updated 2024 Mar. From ASHP website. Updates may be available at ASHP website. https://www.ashp.org/standardize4safety

250. ASHP. Standardize 4 Safety: adult continuous infusion standard. Updated 2024 Mar. From ASHP website. Updates may be available at ASHP website. https://www.ashp.org/standardize4safety

HID. Trissel LA. Handbook on Injectable Drugs. Bethesda, MD: American Society of Health-System Pharmacists.

b. Eli Lilly and Company. Humalog (insulin lispro) injection prescribing information. Indianapolis, IN; 2002 May 31.

c. Eli Lilly and Company. Humulin R (insulin human) injection prescribing information. Indianapolis, IN; 2000 Aug. 3.

d. Novo Nordisk Pharmaceuticals Inc.; Novolog (insulin aspart [rDNA origin]) injection prescribing information. Princeton, New Jersey; 2002 May 15.

e. AHFS Drug Information. McEvoy GK, ed. Insulins general statement. Bethesda, MD: American Society of Health-System Pharmacists.

f. Novo Nordisk. Novolin N PenFill patient information. Princeton, NJ; 2000 Feb.

g. Novo Nordisk. Novolin N patient information. Princeton, NJ; 1999 Feb.

h. Novo Nordisk. Novolin 70/30 sterile suspension patient information. Princeton, NJ; 1999 Feb.

i. Eli Lilly and Company. Humulin N sterile suspension patient information. Indianapolis, IN; 2000 Aug.

j. Novo Nordisk. Novolin R patient information. Princeton, NJ; 1999 Feb.

k. Eli Lilly and Company. Humulin 50/50 (human insulin isophane suspension injection and regular human insulin injection) sterile suspension patient information. Indianapolis, IN; 2000 Aug 3.

l. Eli Lilly and Company. Humulin L sterile suspension patient information. Indianapolis, IN; 2000 Aug 3.

m. Eli Lilly and Company. Humulin N Pen sterile suspension patient information. Indianapolis, IN; 2003 Oct.

n. Schilling McCann JA, Publisher. Pharmacists drug handbook. 2nd ed. Philadelphia, PA: Lippincott Williams and Wilkins and American Society of Health-System Pharmacists; 2003.

o. AHFS Drug Information. McEvoy GK, ed. Insulin human. Bethesda, MD: American Society of Health-System Pharmacists.

p. Eli Lilly and Company. Humulin 70/30 pen (human insulin isophane suspension injection and regular human insulin injection) suspension patient information. Indianapolis, IN; 2003 Oct 8.

q. Novo Nordisk. Novolin 70/30 Innolet(human insulin isophane suspension and regular human injection) suspension patient information. Princeton, NJ; 2002.

r. Eli Lilly and Company. Humulin 70/30 (human insulin isophane suspension injection and regular human insulin injection) suspension patient information. Indianapolis, IN; 2000 Aug 3.

s. American Diabetes Association. Insulin administration. Diabetes Care. 2004; 27(Suppl 1):S106-9.

t. Eli Lilly and Company. Humalog (insulin lispro, rDNA origin) injection prescribing information. Indianapolis, IN; 2004 Aug 4.

u. Buelke-Sam J, Byrd RA, Hoyt JA et al. A reproductive and developmental toxicity study in CD rats of LY275585, [Lys(B28),Pro(B29)]-human insulin. J Am Coll Toxicol. 1994; 13:247-60.

v. Campbell PJ, May ME. A practical guide to intensive insulin therapy. Am J Med Sci. 1995; 310:24-30. http://www.ncbi.nlm.nih.gov/pubmed/7604835?dopt=AbstractPlus

w. Eli Lilly and Company. Humalog (insulin lispro, rDNA origin) injection (vial, prefilled pen, cartridges) patient information. Indianapolis, IN; 2007 Sep 6.

x. Pfützner A, Küstner E, Forst T et al for the German Insulin Lispro/IDDM Study Group. Intensive insulin therapy with insulin lispro in patients with type 1 diabetes reduces the frequency of hypoglycemic episodes. Exp Clin Endocrinol Diabetes. 1996; 104:25-30.

y. Ziegler O, Kolopp M, Louis J et al. Self-monitoring of blood glucose and insulin dose alteration in type 1 diabetes mellitus. Diabetes Res Clin Pract. 1993; 21:51-9. http://www.ncbi.nlm.nih.gov/pubmed/8253023?dopt=AbstractPlus

z. Olefsky JM. Diabetes mellitus. In: Wyngaarden JB, Smith LH Jr, Bennett JC, eds. Cecil textbook of medicine. 19th ed. Philadelphia: WB Saunders Company; 1992:1291-310.

aa. Foster DW. Diabetes mellitus. In: Fauci AS, Braunwald E, Isselbacher KJ et al, eds. Harrison’s principles of internal medicine. l4th ed. New York: McGraw-Hill, Inc; 1998:2060-81.

bb. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993; 329:977-86. http://www.ncbi.nlm.nih.gov/pubmed/8366922?dopt=AbstractPlus

cc. American Society of Health-System Pharmacists. ASHP therapeutic position statement on strict glycemic control in selected patients with insulin-dependent diabetes mellitus. Am J Health-Syst Pharm. 1995; 52:2709-11. http://www.ncbi.nlm.nih.gov/pubmed/8601269?dopt=AbstractPlus

dd. Reichard P, Nilsson BY, Rosenqvist U. The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med. 1993; 329:304-9. http://www.ncbi.nlm.nih.gov/pubmed/8147960?dopt=AbstractPlus

ee. Carlisle BA, Kroon LA, Koda-Kimble MA. Diabetes mellitus. In: Young LY, Koda-Kimble MA, eds. Applied therapeutics: the clinical use of drugs. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:50-1–50-86.

ff. Davis SN, Granner DK. Insulin, oral hypoglycemic agents, and the pharmacology of the endocrine pancreas. In: Hardman JG, Limbird LE, Molinoff PB et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill; 1996:1487-517.

gg. Pampanelli S, Torlone E, Lalli C et al. Improved postprandial metabolic control after subcutaneous injection of a short-acting insulin analog in IDDM of short duration with residual pancreatic β-cell function. Diabetes Care. 1995; 18:1452-9. http://www.ncbi.nlm.nih.gov/pubmed/8722069?dopt=AbstractPlus

hh. American Diabetes Association. Implications of the diabetes control and complications trial. Diabetes Care. 1997; 20(Suppl 1):S620-4.

ii. Henry RR, Genuth S. Forum one: current recommendations about intensification of metabolic control in non–insulin-dependent diabetes mellitus. Ann Intern Med. 1996; 124:175-7. http://www.ncbi.nlm.nih.gov/pubmed/8554214?dopt=AbstractPlus

jj. Betz JL. Fast-acting human insulin analogs: a promising innovation in diabetes care. Diabetes Educ. 1995; 21:195, 197-8, 200. http://www.ncbi.nlm.nih.gov/pubmed/7758386?dopt=AbstractPlus

kk. Trautmann ME. Effect of the insulin analogue [LYS (B28),PRO(B29)] on blood glucose control. Horm Metab Res. 1994; 26:588-90. http://www.ncbi.nlm.nih.gov/pubmed/7705764?dopt=AbstractPlus

ll. American Diabetes Association. Tests of glycemia in diabetes. Diabetes Care. 2002; 25(Suppl 1):S97-9.

mm. Burge MR, Castillo KR, Schade DS. Meal composition is a determinant of lispro-induced hypoglycemia in IDDM. Diabetes Care. 1997; 20:152-5. http://www.ncbi.nlm.nih.gov/pubmed/9118763?dopt=AbstractPlus

nn. Tuominen JA, Karonen SL, Melamies L et al. Exercise-induced hypoglycaemia in IDDM patients treated with a short-acting insulin analogue. Diabetologia. 1995; 38:106-11. http://www.ncbi.nlm.nih.gov/pubmed/7744214?dopt=AbstractPlus

oo. Bohannon NJV, Jack DB. Type II diabetes: tips for managing your older patients. Geriatrics. 1996; 51(March):28-30,33-35. http://www.ncbi.nlm.nih.gov/pubmed/8641590?dopt=AbstractPlus

pp. Diabetes Control and Complications Trial Research Group. Hypoglycemia in the diabetes control and complications trial. Diabetes. 1997; 46:271-86. http://www.ncbi.nlm.nih.gov/pubmed/9000705?dopt=AbstractPlus

qq. Paterson KR, Paice BJ, Lawson DH. Undesired effects of insulin therapy. Adverse Drug React Acute Poisoning Rev. 1983; 2:219-34.

rr. Cryer PE, Gerich JE. Glucose counterregulation, hypoglycemia, and intensive insulin therapy in diabetes mellitus. N Engl J Med. 1985; 313:232-41. http://www.ncbi.nlm.nih.gov/pubmed/2861565?dopt=AbstractPlus

ss. Santiago JV. Intensive management of insulin dependent diabetes: risks, benefits, and unanswered questions. J Clin Endocrinol Metab. 1992; 75:977-82. http://www.ncbi.nlm.nih.gov/pubmed/1400891?dopt=AbstractPlus

tt. Anon. Hypoglycemia: a pitfall of insulin therapy. West J Med. 1983; 139:688-95. http://www.ncbi.nlm.nih.gov/pubmed/6362204?dopt=AbstractPlus

uu. Bergenstal R, Spencer M, Castle G et al. Intensive insulin management of type I and type II diabetes: a comparison of [Lys(B28), Pro(B29) human insulin] (LP) and regular human insulin (REG). Diabetes. 1994; 43(Suppl 1):157A.

vv. Anderson JH Jr, Brunelle RL, Keohane P et al. Mealtime treatment with insulin analog improves postprandial hyperglycemia and hypoglycemia in patients with non-insulin-dependent diabetes mellitus. Arch Intern Med. 1997; 157:1249-55. http://www.ncbi.nlm.nih.gov/pubmed/9183237?dopt=AbstractPlus

ww. Anderson JH Jr, Brunelle RL, Koivisto VA et al et al. Reduction of postprandial hyperglycemia and frequency of hypoglycemia in IDDM patients on insulin-analog treatment. Diabetes. 1997; 46:265-70. http://www.ncbi.nlm.nih.gov/pubmed/9000704?dopt=AbstractPlus

xx. Campbell RK, Campbell LK, White JR. Insulin lispro: its role in the treatment of diabetes mellitus. Ann Pharmacother. 1996; 30:1263-71. http://www.ncbi.nlm.nih.gov/pubmed/8913409?dopt=AbstractPlus

yy. Cohen P, Barzilai N, Lerman A et al. Insulin effects on glucose and potassium metabolism in vivo: evidence for selective insulin resistance in humans. J Clin Endocrinol Metab. 1991; 73:564-8. http://www.ncbi.nlm.nih.gov/pubmed/1874934?dopt=AbstractPlus

zz. Henrichs HR, Unger H, Trautmann ME et al. Severe insulin resistance treated with insulin lispro. Lancet. 1996; 348:1248. http://www.ncbi.nlm.nih.gov/pubmed/8898065?dopt=AbstractPlus

aaa. Lahtela JT, Knip M, Paul R et al. Severe antibody-mediated human insulin resistance: successful treatment with the insulin analog lispro. Diabetes Care. 1997; 20:71-3. http://www.ncbi.nlm.nih.gov/pubmed/9028697?dopt=AbstractPlus

bbb. MacCuish AC, Munro JF, Duncan LJP. Treatment of hypoglycaemic coma with glucagon, intravenous dextrose, and mannitol infusion in a hundred diabetics. Lancet. 1970; 2:946-9. http://www.ncbi.nlm.nih.gov/pubmed/4097595?dopt=AbstractPlus

ccc. American Diabetes Association. Preconception care of women with diabetes. Diabetes Care. 2004; 27(Suppl 1):S76-8.

ddd. Yoo J, Peter S, Kleinfeld M. Transient hypoglycemic hemiparesis in an elderly patient. J Am Geriatr Soc. 1986; 34:479-81. http://www.ncbi.nlm.nih.gov/pubmed/3517115?dopt=AbstractPlus

eee. Reviewers’ comments (personal observations) [Insulins General Statement].

fff. Apstein CS. Glucose-insulin-potassium for acute myocardial infarction: remarkable resluts from a new prospective, randomized trial. Circulation. 1998; 98:2223-6. http://www.ncbi.nlm.nih.gov/pubmed/9826307?dopt=AbstractPlus

ggg. Zimmerman B, Espenshade J, Fujimoto W et al. The pharmacological treatment of hyperglycemia in NIDDM. Diabetes Care. 1995; 18:1510-18. http://www.ncbi.nlm.nih.gov/pubmed/8722084?dopt=AbstractPlus

hhh. Florence JA, Yeager BF. Treatment of type 2 diabetes mellitus. Am Fam Physician. 1999; 59:2835-44. http://www.ncbi.nlm.nih.gov/pubmed/10348076?dopt=AbstractPlus

iii. American Diabetes Association. Hyperglycemic crises in patients with diabetes mellitus. Diabetes Care. 2004; 27(Suppl 1):S94-102.

jjj. Scott JF, Robinson GM, French JM et al. Glucose potassium insulin infusions in the treatment of acute stroke patients with mild to moderate hyperglycmia: the glucose insulin in stroke trial (GIST). Stroke. 1999; 30:793-9. http://www.ncbi.nlm.nih.gov/pubmed/10187881?dopt=AbstractPlus

kkk. Adams HP, Adams RJ, Brott T et al. Guidelines for the early management of patients with ischemic stroke: a scientific statement from the Stroke Council of the American Stroke Association. Stroke. 2003; 34:1056-83. http://www.ncbi.nlm.nih.gov/pubmed/12677087?dopt=AbstractPlus

lll. Clement SS, Braithwaite SS, Mager MF et al. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004; 27:553-91. http://www.ncbi.nlm.nih.gov/pubmed/14747243?dopt=AbstractPlus

mmm. Silverstein J, Klingensmith G, Copeland K et al. Care of children and adolescents with type 1 diabetes. Diabetes Care. 2005; 28:186-212. http://www.ncbi.nlm.nih.gov/pubmed/15616254?dopt=AbstractPlus

nnn. Novo Nordisk. Novolin R (insulin human regular) injection prescribing information. Princeton, NJ; 2005 Oct.

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