Insulin information from DrugsUpdate
P - Caution when used during pregnancy
L - Caution when used during lactation
Insulin is a hormone that is central to regulating energy and glucose metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle.
Insulin stops the use of fat as an energy source. When insulin is absent, glucose is not taken up by body cells and the body begins to use fat as an energy source, for example, by transfer of lipids from adipose tissue to the liver for mobilization as an energy source. As its level is a central metabolic control mechanism, its status is also used as a control signal to other body systems (such as amino acid uptake by body cells). In addition, it has several other anabolic effects throughout the body.
When control of insulin levels fails, diabetes mellitus will result. As a consequence, insulin is used medically to treat some forms of diabetes mellitus. Patients with Type 1 diabetes mellitus depend on external insulin (most commonly injected subcutaneously) for their survival because the hormone is no longer produced internally. Patients with Type 2 diabetes mellitus are insulin resistant, and because of such resistance, may suffer from a relative insulin deficiency. Some patients with Type 2 diabetes may eventually require insulin if other medications fail to control blood glucose levels adequately, though this is somewhat uncommon.
Insulin also influences other body functions, such as vascular compliance and cognition. Once insulin enters the human brain, it enhances learning and memory and in particular benefits verbal memory.
Insulin is a peptide hormone composed of 51 amino acids and has a molecular weight of 5808 Da. It is produced in the islets of Langerhans in the pancreas. The name comes from the Latin insula for "island". Insulin's structure varies slightly between species of animal. Insulin from animal sources differs somewhat in "strength" (in carbohydrate metabolism control effects) in humans because of those variations. Porcine (pig) insulin is especially close to the human version.
Pharmacodynamics
Receptor-bound insulin lowers blood glucose by facilitating cellular uptake of glucose into skeletal muscle and fat, and inhibiting the output of glucose from the liver. Receptor-bound insulin also inhibits lipolysis in adipocytes, inhibits proteolysis, and enhances protein synthesis.
Pharmacokinetics
Absorption
Insulin aspart mix
C max is about 23 milliunits/L. T max is about 1 h.
Insulin detemir
T max is 6 to 8 h. Absolute bioavailability is 60%.
Insulin glulisine
C max is about 83 microunits/mL. T max is about 60 to 100 min. Absolute bioavailability is 70%.
Insulin lispro
Absolute bioavailability is 55% to 77%.
Insulin lispro mix 75/25
T max ranged from 30 to 240 min in patients with type 1 diabetes.
Insulin lispro mix 50/50
T max ranged from 45 to 120 min in patients with type 1 diabetes.
Distribution
Insulin aspart
0% to 9% bound to plasma proteins.
Insulin detemir
98% bound to albumin.
Insulin glulisine
Vd is 13 L.
Insulin lispro
Vd ranges from 0.26 to 0.36 L/kg.
Elimination
Insulin aspart
Cl is 1.22 L/h/kg. The half-life is 81 min.
Insulin aspart mix
The half-life is 8 to 9 h.
Insulin detemir
The half-life is 5 to 7 h (dose dependent). Vd is 0.1 L/kg.
Insulin glulisine
The half-life is 13 min after IV administration and 42 min after subcutaneous administration. Vd is 13 L.
Insulin lispro
The half-life is 1 h.
Peak
Insulin aspart
1 to 3 h.
Insulin aspart mix
1 to 4 h.
Insulin detemir
6 to 8 h.
Insulin glulisine
55 min.
Insulin lispro
0.5 to 1.5 h.
Duration
Insulin aspart
3 to 5 h.
Insulin aspart mix
Serum insulin levels return to baseline in about 12 h.
Insulin detemir
5.7 to 23.2 h (dose dependent).
Insulin glargine
24 h.
Special Populations
Renal Function Impairment
Insulin Cl may be reduced in patients with impaired renal function.
Insulin aspart, insulin detemir
Renal function impairment does not appear to affect the pharmacokinetics.
Insulin aspart mix, insulin lispro mix
Effects of renal function impairment on pharmacokinetics have not been studied.
Hepatic Function Impairment
Insulin aspart
No correlation between degree of hepatic failure and pharmacokinetics.
Insulin aspart mix, insulin glulisine, insulin lispro mix
Effects of hepatic function impairment on pharmacokinetics have not been studied.
Elderly
Insulin aspart mix, insulin lispro, insulin lispro mix
Effects of age on pharmacokinetics have not been studied.
Insulin detemir
The AUC was 35% higher in healthy, elderly patients (68 yr of age and older) compared with younger patients (25 to 35 yr of age) because of reduced Cl in elderly patients. Higher insulin detemir AUC levels in elderly patients because of reduced Cl.
Children
Insulin aspart, insulin glulisine
Pharmacokinetics in children and adolescents with type 1 diabetes are similar to those of healthy adults and adults with type 1 diabetes.
Insulin aspart mix, insulin lispro, insulin lispro mix
Pharmacokinetics have not been studied in children and adolescents.
Insulin detemir
AUC and C max were higher by 10% and 24%, respectively, in children (6 to 12 yr of age) compared with adolescents and adults.
Obesity Insulin aspart
Cl is reduced 28% in patients with a body mass index (BMI) more than 32 kg/m 2 compared with patients with a BMI less than 23 kg/m 2 .
Insulin aspart mix, insulin lispro, insulin lispro mix
Effects of obesity on pharmacokinetics have not been studied.
Insulin glulisine
T max occurs faster and C max is greater with insulin glulisine compared with regular human insulin.
Insulin Indications / Insulin Uses
Information Not Available
Insulin Adverse Reactions / Insulin Side Effects
CNS
Headache, neuropathy, seizure, sensory disturbances.
Dermatologic
Lipodystrophy (from repeated insulin injection into same site), pruritus, rash, skin disorder.
EENT
Diabetic retinopathy, nasopharyngitis.
GI
Abdominal pain, diarrhea, nausea.
Genitourinary
UTI.
Hypersensitivity
Hypersensitivity reaction (including anaphylaxis, angioedema, elevated alkaline phosphatase, fast pulse, hypotension, rash, shortness of breath, sweating), insulin antibody production.
Lab Tests
Elevated alkaline phosphatase.
Local
Catheter occlusions, infusion-site reactions, itching at injection site, redness, swelling.
Metabolic-Nutritional
Hypoglycemia, hypokalemia, weight gain.
Respiratory
Upper respiratory tract infection.
Miscellaneous
Accidental injury, chest pain, hyporeflexia, influenza, onychomycosis, peripheral edema.
Precautions
Monitor
Check blood sugar frequently and observe for signs of hypoglycemia and hyperglycemia. Check potassium levels closely when administering IV. Periodically measure glycosylated hemoglobin (A 1c ) to monitor long-term glycemic control. Check urine for ketones in patients at risk for ketoacidosis and observe for signs and symptoms of ketoacidosis (eg, drowsiness, frequent urination, fruit-like breath, thirst).
Other Drug Interactions
Possible absence of hypoglyaemic warning symptoms with b blockers.
Decreased hypoglycaemic effect with corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, phenothiazine derivatives, somaropin, sympathomimtic reagents, thyroid hormones, oestrogens, progestins (e.g. in ral contraceptives), protease inhibitors and atypical antipsychotic (e.g. olanzapine and clozapine). Increased hypoglycaemic efect with oral antidiabetic agents, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAOIs, pentoxifylline, propaxyphne, salicylates and sulfonamide antibiotics.
Decreased insulin resistance with octreotide and lanreotide.
Increased risk of weight gain and peripheral oedemawith pioglitazone, rosiglitazone.
Decreased effect of sermorelin.
Other Interactions
Information Not Available
Dosage
Information Not Available
Food(before/after)
Information Not Available
List of Contraindications
Insulin and Pregnancy
Category B (insulin aspart, insulin lispro, insulin lispro mix); Category C (insulin aspart mix, insulin detemir, insulin glargine, insulin glulisine).
Insulin and Lactation
Undetermined.
Insulin and Children
Safety and efficacy not established (insulin aspart mix, insulin lispro mix). Safety and efficacy not established in children younger than 6 yr of age with type 1 diabetes (insulin glargine). Safety and efficacy not established in children younger than 4 yr of age with type 1 diabetes (insulin glulisine). In studies in children 3 to 11 yr of age and adolescents 9 to 19 yr of age, comparable glycemic control was achieved regardless of treatment group (insulin lispro).
Insulin and Geriatic
Effects of age on onset have not been determined (insulin aspart, insulin aspart mix, insulin lispro). The initial dose, dose increments, and maintenance dosage should be conservative (insulin detemir, insulin glargine). Use caution when making dose selection, usually starting at the lower end of the dosing range, reflecting comorbidity and the greater frequency of decreased hepatic and renal function. Hypoglycemia may be difficult to recognize in elderly patients.
Insulin and Other Contraindications
Information Not Available
Storage
Insulin aspart, insulin lispro
Store unopened vials, cartridges, pens, and prefilled syringes in refrigerator between 36° and 46°F until expiration date, or at room temperature below 86°F for up to 28 days. Do not freeze. Store opened vials below 86°F for up to 28 days. May be refrigerated. Store punctured cartridges, pens, or prefilled syringes below 86°F for up to 28 days. Do not refrigerate. Do not expose to excessive heat or sunlight. Humalog 3 mL cartridge used in the D-Tron or D-Tron plus should be discarded after 7 days, even if it still contains Humalog . For insulin aspart mix, store vials in refrigerator between 36° and 46°F or below 86°F for up to 28 days. Do not freeze. Protect from heat and light. Store unpunctured cartridges and prefilled syringes between 36° and 46°F. Protect from light. Store punctured cartridges and prefilled syringes below 86°F for up to 14 days. Do not refrigerate. Protect from direct heat and light.
Insulin aspart mix (eg, 70/30)
Store unopened vials and pens in refrigerator (36° to 46°F). Protect from freezing. Do not use if frozen. Vial in use can be stored outside refrigerator at temperature less than 86°F and away from direct heat and light, but discard any unused insulin after 28 days. Pens in use must not be stored in refrigerator. Pens in use can be used for 14 days if stored at room temperature (below 86°F).
Insulin detemir
Store unopened vials, cartridges, and prefilled syringes in refrigerator (36° to 46°F) until expiration date, or for up to 42 days at room temperature (below 86°F). Store in-use vials in refrigerator or at room temperature (below 86°F) for up to 42 days. Store in-use cartridges or prefilled syringes at room temperature for up to 42 days. Do not store in-use cartridges or prefilled syringes in refrigerator or with needle in place. Protect all doseforms from freezing, direct heat, and direct light. Discard if frozen. Discard 42 days after first use.
Insulin glargine
Do not store in freezer or allow to freeze. Discard if frozen. Unopened vial, cartridge system, and disposable device should be stored in refrigerator, at 36° to 46°F. Opened vials, whether or not refrigerated, must be used within 28 days. Store open vials below 86°F. Protect from direct heat and light. Open cartridge system in OptiClik should not be refrigerated, but should be kept at room temperature (below 86°F), away form direct heat and light; discard after 28 days. Open disposable insulin device should not be refrigerated, but should be stored below 86°F, away from direct heat and light. Discard after 28 days.
Insulin glulisine
Store unopened vials, pens, and cartridge system at 36° to 46°F. Protect from light and freezing. Discard if frozen. Store opened vials and cartridge system at 36° to 46°F or at room temperature (below 77°F), and protect from direct heat and light. Discard 28 days after opening. Do not store opened cartridges inserted in OptiClik or opened pens in refrigerator. Store below 77°F and discard 28 days after first use. Do not store insulin delivery device for cartridges in refrigerator at any time. Discard infusion sets (eg, catheter, reservoirs, tubing) and insulin glulisine in reservoir after no more than 48 h of use, or after exposure to temperatures more than 98.6°F. Infusion bags are stable at room temperature for 48 h.
Insulin lispro mix 50/50, insulin lispro mix 75/25
Store unopened vials in the refrigerator between 36° and 46°F, or at room temperature (below 86°F) for 28 days. Do not freeze. Protect from direct heat and light. Store unopened pens in the refrigerator between 36° and 46°F until expiration date, or at room temperature (below 86°F) for 10 days. Protect from direct heat and light. Store open vials below 86°F for 28 days. May be refrigerated, but do not freeze. Store open pens below 86°F for 10 days. Do not refrigerate. Protect from direct heat and light.
Lab interference
Insulin aspart, insulin lispro
Store unopened vials, cartridges, pens, and prefilled syringes in refrigerator between 36° and 46°F until expiration date, or at room temperature below 86°F for up to 28 days. Do not freeze. Store opened vials below 86°F for up to 28 days. May be refrigerated. Store punctured cartridges, pens, or prefilled syringes below 86°F for up to 28 days. Do not refrigerate. Do not expose to excessive heat or sunlight. Humalog 3 mL cartridge used in the D-Tron or D-Tron plus should be discarded after 7 days, even if it still contains Humalog . For insulin aspart mix, store vials in refrigerator between 36° and 46°F or below 86°F for up to 28 days. Do not freeze. Protect from heat and light. Store unpunctured cartridges and prefilled syringes between 36° and 46°F. Protect from light. Store punctured cartridges and prefilled syringes below 86°F for up to 14 days. Do not refrigerate. Protect from direct heat and light.
Insulin aspart mix (eg, 70/30)
Store unopened vials and pens in refrigerator (36° to 46°F). Protect from freezing. Do not use if frozen. Vial in use can be stored outside refrigerator at temperature less than 86°F and away from direct heat and light, but discard any unused insulin after 28 days. Pens in use must not be stored in refrigerator. Pens in use can be used for 14 days if stored at room temperature (below 86°F).
Insulin detemir
Store unopened vials, cartridges, and prefilled syringes in refrigerator (36° to 46°F) until expiration date, or for up to 42 days at room temperature (below 86°F). Store in-use vials in refrigerator or at room temperature (below 86°F) for up to 42 days. Store in-use cartridges or prefilled syringes at room temperature for up to 42 days. Do not store in-use cartridges or prefilled syringes in refrigerator or with needle in place. Protect all doseforms from freezing, direct heat, and direct light. Discard if frozen. Discard 42 days after first use.
Insulin glargine
Do not store in freezer or allow to freeze. Discard if frozen. Unopened vial, cartridge system, and disposable device should be stored in refrigerator, at 36° to 46°F. Opened vials, whether or not refrigerated, must be used within 28 days. Store open vials below 86°F. Protect from direct heat and light. Open cartridge system in OptiClik should not be refrigerated, but should be kept at room temperature (below 86°F), away form direct heat and light; discard after 28 days. Open disposable insulin device should not be refrigerated, but should be stored below 86°F, away from direct heat and light. Discard after 28 days.
Insulin glulisine
Store unopened vials, pens, and cartridge system at 36° to 46°F. Protect from light and freezing. Discard if frozen. Store opened vials and cartridge system at 36° to 46°F or at room temperature (below 77°F), and protect from direct heat and light. Discard 28 days after opening. Do not store opened cartridges inserted in OptiClik or opened pens in refrigerator. Store below 77°F and discard 28 days after first use. Do not store insulin delivery device for cartridges in refrigerator at any time. Discard infusion sets (eg, catheter, reservoirs, tubing) and insulin glulisine in reservoir after no more than 48 h of use, or after exposure to temperatures more than 98.6°F. Infusion bags are stable at room temperature for 48 h.
Insulin lispro mix 50/50, insulin lispro mix 75/25
Store unopened vials in the refrigerator between 36° and 46°F, or at room temperature (below 86°F) for 28 days. Do not freeze. Protect from direct heat and light. Store unopened pens in the refrigerator between 36° and 46°F until expiration date, or at room temperature (below 86°F) for 10 days. Protect from direct heat and light. Store open vials below 86°F for 28 days. May be refrigerated, but do not freeze. Store open pens below 86°F for 10 days. Do not refrigerate. Protect from direct heat and light.
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