II. Definitions
-
Insulin
- Insulin is a polypeptide produced by pancreatic beta cells, with release stimulated by Blood Glucose concentration
- Insulin promotes energy utilization via Glycolysis, and energy storage as glycogen, Protein and Triglycerides
- First used in Diabetes Mellitus in 1922, by Drs Banting and Best
- Bolus Insulin (short-acting)
- Similar to physiologic Insulin, with immediate onset (15-30 min) and short duration (2 to 4 hours)
- Primarily covers short-term Blood Glucose spikes with meals
-
Basal insulin (long-acting)
- Long-acting coverage to maintain Blood Glucose control throughout the day, between meals
- Mimics the low level continuous Insulin release by a normal human Pancreas
- Insulin Glargine (Lantus) and similar agents that last approximately 24 hours have largely replaced NPH Insulin (12 hour duration)
- Insulin Analog
III. Indications
- Type 1 Diabetes Mellitus
- Type 2 Diabetes Mellitus with Insulin Resistance refractory to non-Insulin therapy
- Acute Hyperkalemia Management
- Acute Pancreatitis due to severe Hypertriglyceridemia (>1000 mg/dl)
- Calcium Channel Overdose (or Beta Blocker Overdose)
IV. Mechanism
- See Insulin
V. Medications: Bolus Insulins (Meal-time Insulin)
- Precautions: Humulin R U-500 is NOT a Bolus Insulin (NOT equivalent to Bolus Insulins listed below)
- Humulin R U-500 is a Regular Insulin that is at 5-fold higher concentration than typical Regular Insulin
- At this very high concentration, Humulin R U-500 has Pharmacokinetics that are more like a mixed or Basal insulin
- Despite being Regular Insulin, U-500 acts more like NPH or Insulin 70/30
- Traditional Insulins
- Regular Insulin (Novolin R, Humulin R)
- Onset: 15 to 30 minutes
- Peak: 2.5 to 5 hours
- Duration: 6 to 8 hours
- Avoid in Stage IV or Stage V significant Chronic Kidney Disease
- Avoid if history of severe Hypoglycemia
- Available concentrations
- Humulin R U-100 (100 units/ml, orange)
- Humulin R U-500 (500 units/ml, green)
- High concentration AND basal and Bolus Insulin activity (similar to 70/30)
- See Basal insulins below for description
- Regular Insulin (Novolin R, Humulin R)
- Analog Insulins (Rapid, consistent absorption)
- Glulisine (Apidra)
- Onset: 5 to 15 minutes
- Peak: 1 to 2 hours
- Duration: 3 to 5 hours
- Similar to other bolus analogues
- FDA approved for chilren (age>4 years) and adults, and to take after meal
- Other analogs expected with same effect after meal
- Lispro (Humalog, Admelog)
- Onset: 5 to 15 minutes
- Peak: 1 to 2 hours
- Duration: 3 to 5 hours
- FDA approved for age >3 years
- Concentrations
- Humalog U-100 (100 units/ml) vial or KwikPen
- Humalog U-200 (200 units/ml) KwikPen - for patients using >20 units/day
- Lispro-aabc (Lyumjev)
- Same manufacturer as Humalog
- Four letter designation refers to new FDA labeling of Insulins as biologics
- Marketed as 10 minutes faster onset that typical Lispro Insulin
- Unlikely to offer any real benefit over other Lispro Insulin
- Concentrations
- Lyumjev U-100 (100 units/ml) vial or KwikPen
- Lyumjev U-200 (200 units/ml) KwikPen - for patients using >20 units/day
- Aspart (Novolog, Fiasp)
- FDA approved for age >2 years
- Onset: 5 to 15 minutes
- Peak: 1 to 2 hours
- Duration: 3 to 5 hours
- Glulisine (Apidra)
VI. Dosing
- Precautions
- Humulin R U-500 is NOT a Bolus Insulin (see above)
- Carefully check Insulin type and concentration before dose
- Serious dosing errors due to concentration (100 units/ml or 200 units/ml) may occur
- Confirm pen or bottle formulation (Bolus Insulin or Basal insulin)
- Subcutaneous
- See Insulin Dosing
- See Insulin Dosing in Type I Diabetes
- See Insulin Dosing in Type II Diabetes
- See Carbohydrate Count in Insulin Dosing
- See Carbohydrate Counting
- Administer analog Insulins (e.g. Lispro) 15 min before meals, and Regular Insulin 30 min before meals
- Only NPH Insulin may be mixed in same syringe with bolus/rapid Insulins (draw up Bolus Insulin first)
- Do NOT mix other basal/Long-Acting Insulins (e.g. Glargine) with Bolus Insulins
- Typical daily dosing
- Total daily Insulin
- Type 1 Diabetes: 0.3 to 0.5 units/kg (up to 0.5 to 1.0 units/kg in children)
- Type 2 Diabetes: 1 to 1.5 units/kg
- Bolus Insulin dose
- Give 50% of total Insulin daily units as Bolus Insulin divided over 3 meals
- Give remaining 50% of total daily dose as Basal insulin (e.g. Insulin Glargine or Lantus)
- Total daily Insulin
- Initiating Insulin in Type 2 Diabetes
- Start 0.1 units/kg OR 4 units OR 10% of basal dose, given before the largest meal
- Titrate doses 1-2 units (or 10-15%) every 3 to 7 days
- Combine with Basal insulin (roughly 50% of total daily Insulin)
- Intravenous Regular Insulin
- Intravenous insulin Pharmacokinetics (other listed kinetics above is for subcutaneous dosing)
- Onset: Immediate
- Half-Life: 5-10 minutes
- Insulin Infusion in severe Hyperglycemia
- See Insulin Drip
- See Diabetic Ketoacidosis Management in Adults
- See Diabetic Ketoacidosis Management in Children
- See Diabetic Ketoacidosis in Pregnancy
- See Hyperosmolar Hyperglycemic State
- Do NOT start Insulin replacement until Hypokalemia is corrected
- Initial Insulin Bolus (optional): 0.1 units/kg Regular Insulin IV
- Insulin IV Infusion: Start at 0.1 units/kg/hour IV using a 1 unit/ml solution (100 units/100 ml NS)
- See specific conditions for emergent Insulin use outside of diabetes
- Acute Hyperkalemia Management
- Acute Pancreatitis due to severe Hypertriglyceridemia (>1000 mg/dl)
- Calcium Channel Overdose (or Beta Blocker Overdose)
- Intravenous insulin Pharmacokinetics (other listed kinetics above is for subcutaneous dosing)
-
Insulin Pump
- FDA approved Bolus Insulins for Insulin Pump: Humalog, Novolog, Apidra, Admelog
- Do NOT mix Insulins in the Insulin Pump
- Only use an approved Bolus Insulin at standard concentration (100 units/ml)
VII. Adverse Effects
- See Insulin
-
Hypoglycemia
- Increased risk when Hemoglobin A1C <7.4%
- Decreased risk with analogue Insulins
- Higher risk with severe Renal Insufficiency
- Insulin is excreted by the Kidney (30% of total)
- Gluconeogenesis occurs in the Kidney (30% of total)
- Weight gain (Excess of 4 kg over 10 years)
- Lipohypertrophy
- Localized fat hypertrophy and scar tissue from repeated injections in the same area
- Results in variable Insulin absorption as below
- Prevent by rotating injection sites (see below)
- Medical providers should examine injection sites
- Variable Insulin absorption
- Insulin absorption varies by body site
- Variable absorption at lipohypertrophy sites
- Poor absorption causes early postprandial Hyperglycemia
- Depot formation causes delayed Hypoglycemia
- Site rotation (prevents lipohypertrophy - see above)
VIII. Safety
- Considered safe in pregnancy and Lactation
IX. Reources
X. References
- (2014) Presc Lett 21(12): 69
- Lepore (2000) Diabetes 49:2142-8 [PubMed]
- Mayfield (2004) Am Fam Physician 70(3):489-512 [PubMed]
Images: Related links to external sites (from Bing)
Related Studies
novolin r (on 4/20/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
NOVOLIN R 100 UNIT/ML FLEXPEN | OTC | $16.64 per ml |
NOVOLIN R 100 UNIT/ML VIAL | OTC | $13.26 per ml |
humulin r (on 5/18/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
HUMULIN R 100 UNIT/ML VIAL | OTC | $14.27 per ml |
HUMULIN R 500 UNIT/ML KWIKPEN | $91.89 per ml | |
HUMULIN R 500 UNIT/ML VIAL | $71.14 per ml | |
novolog (on 2/23/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
NOVOLOG 100 UNIT/ML FLEXPEN | $35.80 per ml | |
NOVOLOG 100 UNIT/ML VIAL | $27.80 per ml | |
NOVOLOG MIX 70-30 FLEXPEN | $35.73 per ml | |
NOVOLOG MIX 70-30 VIAL | $28.93 per ml | |
NOVOLOG PENFILL 100 UNIT/ML | $34.48 per ml | |
fiasp (on 10/19/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
FIASP 100 UNIT/ML FLEXTOUCH | $35.73 per ml | |
FIASP 100 UNIT/ML VIAL | $27.71 per ml | |
FIASP PENFILL 100 UNIT/ML CART | $34.36 per ml | |
humalog (on 4/20/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
HUMALOG 100 UNIT/ML CARTRIDGE | $32.57 per ml | |
HUMALOG 100 UNIT/ML KWIKPEN | $33.94 per ml | |
HUMALOG 100 UNIT/ML VIAL | $26.36 per ml | |
HUMALOG 200 UNIT/ML KWIKPEN | $67.89 per ml | |
HUMALOG JR 100 UNIT/ML KWIKPEN | $34.03 per ml | |
HUMALOG MIX 50-50 KWIKPEN | $33.87 per ml | |
HUMALOG MIX 50-50 VIAL | $27.45 per ml | |
HUMALOG MIX 75-25 KWIKPEN | $33.92 per ml | |
HUMALOG MIX 75-25 VIAL | $27.31 per ml | |
HUMALOG TEMPO PEN 100 UNIT/ML | $33.94 per ml | |
admelog (on 1/1/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
ADMELOG 100 UNIT/ML VIAL | $9.43 per ml | |
ADMELOG SOLOSTAR 100 UNIT/ML | $12.13 per ml | |
lyumjev (on 8/17/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
LYUMJEV 100 UNIT/ML KWIKPEN | $33.91 per ml | |
LYUMJEV 100 UNIT/ML VIAL | $26.14 per ml | |
LYUMJEV 200 UNIT/ML KWIKPEN | $67.63 per ml | |
apidra (on 5/18/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
APIDRA 100 UNIT/ML VIAL | $27.18 per ml | |
APIDRA SOLOSTAR 100 UNIT/ML | $35.13 per ml |
Ontology: Insulin, Aspart, Human (C0123677)
Concepts | Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116) , Hormone (T125) |
SnomedCT | 388452006, 325072002 |
English | insulin aspart, INSULIN ASPART, human insulin aspart, human insulin aspart (medication), aspart insulin, Insulin, Aspart, Human, Insulin aspart (substance), Insulin aspart, Aspart insulin (product), Aspart insulin, INSULIN,ASPART,HUMAN/rDNA, Insulin Aspart |
Spanish | insulina aspart, insulina asparta, insulina aspártica, insulina asparta (sustancia), insulina asparta (producto), insulina aspart (producto), insulina aspart (sustancia) |
Ontology: Insulin Lispro (C0293359)
Definition (MSH) | Insulin that has been modified so that the B-chain contains a LYSINE at position 28 instead of a PROLINE and a PROLINE at position 29 instead of a LYSINE. |
Definition (NCI) | A recombinant therapeutic agent which is chemically identical to or similar to endogenous human insulin. In lispro insulin, the amino acid proline at B-28 and the amino acid lysine at B-29 are reversed, resulting in the rapid dissolution of this insulin to a monomer that is absorbed rapidly after subcutaneous administration. Lispro insulin is equipotent to human insulin on a molar basis but its effects are faster and of shorter duration. Endogenous insulin, a pancreatic hormone composed of two polypeptide chains, is important in the normal metabolism of carbohydrates, proteins and fats, promoting glucose utilization and protein synthesis; it has anabolic effects on many types of tissues. (NCI04) |
Concepts | Hormone (T125) , Amino Acid, Peptide, or Protein (T116) , Pharmacologic Substance (T121) |
MSH | D061268 |
SnomedCT | 388454007, 412210000, 125703000 |
English | Insulin Lispro, Insulin lispro, insulin lispro, insulin human lispro, lispro human insulin, lispro insulin, lispro, Lispro, 28(B)-Lys-29(B)-Pro-Insulin, LYSPRO, Lispro, Insulin, 28(B)-Lysine-29(B)-Prolineinsulin, Insulin, Lysyl(28B)-Prolyl(28B)-, Insulin, Lys(28B)-Pro(29B)-, Insulin Lispro [Chemical/Ingredient], INSULIN LISPRO, Lispro insulin (product), Lispro insulin, Lispro insulin (substance), INSULIN,LISPRO,HUMAN/rDNA |
French | Insuline Lysyl(28B)-Prolyl(28B), Insuline Lispro, LYSPRO, Insuline 28(B)-Lys-29(B)-Pro, Insuline Lys(28B)-Pro(29B), Insuline 28(B)-Lysine-29(B)-Proline, Lispro |
Portuguese | Insulina Lispro |
Russian | LIZPRO, ЛИЗПРО, INSULIN LIZPRO, ИНСУЛИН ЛИЗПРО, 28(B)-ЛИЗИН-29(B)-ПРОЛИНИНСУЛИН, 28(B)-LIZIN-29(B)-PROLININSULIN |
Spanish | Insulina Lispro, insulina lispro (producto), insulina lispro, insulina lispro (sustancia) |
Czech | inzulin Lispro |
Polish | Insulina lispro |
Italian | Insulina lispro |
German | 28(B)-Lys-29(B)-Pro-Insulin, Insulin, Lysyl(28B)-Prolyl(28B)-, Insulin lispro, Insulin, Lys(28B)-Pro(29B)-, Lys-Pro-Insulin, Lyspro |
Ontology: Insulin, Short-Acting (C0356365)
Definition (MSH) | Insulin derivatives and preparations that are designed to induce a rapid HYPOGLYCEMIC EFFECT. |
Concepts | Pharmacologic Substance (T121) , Hormone (T125) , Amino Acid, Peptide, or Protein (T116) |
MSH | D061266 |
SnomedCT | 126213004, 8780003, 325013000, 411531001 |
English | Rapid-acting insulin preparation, Rapid-Acting Insulin, Short-Acting Insulin, Insulin, Rapid-Acting, Insulin, Rapid Acting, Insulin, Short-Acting, Insulin, Short Acting, Insulin, Short-Acting [Chemical/Ingredient], Rapid-acting insulin product (product), Rapid-acting insulin, Rapid-acting insulin product, Rapid-acting insulin (substance), Short-acting insulin, Short-acting insulin (product), Rapid-acting insulin, NOS, Rapid-acting insulin preparation (substance), Short-acting insulin (substance), Insulin, Rapid-acting, Insulin, Short-acting |
French | Insuline à action rapide, Insuline rapide, Insuline à courte durée d'action, Insuline à effet rapide |
Portuguese | Insulina de Ação Curta |
Russian | ИНСУЛИН БЫСТРОДЕЙСТВУЮЩИЙ, ИНСУЛИН КОРОТКОГО ДЕЙСТВИЯ, INSULIN BYSTRODEISTVUIUSHCHII, INSULIN KOROTKOGO DEISTVIIA |
Spanish | Insulina de Acción Corta, insulina de acción rápida, insulina de acción rápida (sustancia), producto con insulina de acción rápida (producto), producto con insulina de acción rápida, Insulina de Acción Inmediata, insulina de acción corta (producto), insulina de acción corta, preparado insulínico de acción rápida (producto), preparado insulínico de acción rápida (sustancia), preparado insulínico de acción rápida, insulina de acción corta (sustancia) |
Czech | krátkodobě působící inzuliny, krátkodobě působící insuliny, krátkodobě působící inzulíny |
Polish | Insulina krótkodziałająca, Insulina krótko działająca, Analog insuliny krótko działający |
Italian | Insulina rapida |
German | Insulin, kurzwirkendes, Kurz wirkendes Insulin, Kurzwirkendes Insulin, Insulin, schnellwirkendes, Schnell wirkendes Insulin, Schnellwirkendes Insulin |
Ontology: Humalog (C0528249)
Concepts | Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116) |
MSH | D061268 |
English | humalog, HumaLOG, Humalog, Eli Lilly brand of Insulin Lispro |
French | Humalog, Insuline Lispro de marque Eli Lilly |
German | Humalog, Liprolog |
Ontology: Regular Insulin, Human (C0795635)
Definition (MSH) | Regular insulin preparations that contain the HUMAN insulin peptide sequence. |
Concepts | Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116) , Hormone (T125) |
MSH | D061386 |
SnomedCT | 126210001, 96367001, 126216007 |
LNC | LP17001-6 |
English | Insulin Reg Human Semi-Syn, Insulin Reg, Hum S-S Buff, insulin human, Insulin Regular,Human Buffered, Regular Insulin, Human, Human insulin preparation, Insulin human, regular human insulin (Humulin-R), regular human insulin, regular human insulin (medication), insulin regular human recombinant, human insulin, human insulin (medication), INSULIN HUMAN, Insulin, Regular, Human [Chemical/Ingredient], insulin human regular, human regular insulin, Insulin, Regular, Human, insulin regular, human, insulin (human), Semisynthetic human insulin preparation (substance), Semisynthetic human insulin preparation, Human insulin (substance), Human insulin product (product), Human insulin product, Human insulin, Human insulin, NOS, Human insulin preparation (substance), INSULIN,REGULAR,HUMAN BUFFERED, INSULIN,REGULAR,HUMAN/SEMISYNTHETIC, INSULIN,REGULAR,HUMAN/rDNA, Insulin Human |
Spanish | preparado de insulina humana (producto), insulina humana (producto), preparado de insulina humana, Insulina Regular Humana, preparado de insulina humana semisintética (sustancia), preparado de insulina humana semisintética, insulina humana (sustancia), insulina humana, preparado de insulina humana (sustancia) |
French | Insuline ordinaire humaine, Insuline régulière humaine |
Portuguese | Insulina Regular Humana, Insulina Humana Regular |
Russian | ИНСУЛИН ЧЕЛОВЕЧЕСКИЙ РЕГУЛЯР, ХУМУЛИН, INSULIN REGULIAR CHELOVECHESKII, ИНСУЛИН РЕГУЛЯР ЧЕЛОВЕЧЕСКИЙ, KHUMULIN, INSULIN CHELOVECHESKII REGULIAR |
Czech | insulin humánní, inzulin lidský, insulin lidský |
Polish | Insulina zwykła ludzka |
Italian | Insulina regolare umana |
German | Humanes Altinsulin, Humanes Normalinsulin, Insulin, normal, human |
Ontology: NovoLog (C0939412)
Concepts | Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116) |
MSH | D061267 |
English | Novolog, novolog, novorapid, NovoLOG, NovoRapid, Novo Nordisk Brand of Insulin Aspart, NovoLog |
French | NovoLog, Insuline Asparte de la marque Novo Nordisk, NovoRapid |
Czech | NovoLog, NovoRapid |
Italian | NovoRapid, NovoLog, Insulina aspart Novo Nordisk |
German | NovoRapid, NovoLog |
Ontology: Apidra (C1654827)
Concepts | Hormone (T125) , Amino Acid, Peptide, or Protein (T116) , Pharmacologic Substance (T121) |
English | Apidra |