II. Definitions

  1. Insulin
    1. Insulin is a polypeptide produced by pancreatic beta cells, with release stimulated by Blood Glucose concentration
    2. Insulin promotes energy utilization via Glycolysis, and energy storage as glycogen, Protein and Triglycerides
    3. First used in Diabetes Mellitus in 1922, by Drs Banting and Best
  2. Bolus Insulin (short-acting)
    1. Similar to physiologic Insulin, with immediate onset (15-30 min) and short duration (2 to 4 hours)
    2. Primarily covers short-term Blood Glucose spikes with meals
  3. Basal insulin (long-acting)
    1. Long-acting coverage to maintain Blood Glucose control throughout the day, between meals
    2. Mimics the low level continuous Insulin release by a normal human Pancreas
    3. Insulin Glargine (Lantus) and similar agents that last approximately 24 hours have largely replaced NPH Insulin (12 hour duration)
  4. Insulin Analog
    1. Historically, short-acting Regular Insulin has been sourced from animal Pancreas (pigs, cows)
    2. As of the 1980s, human Insulins were synthesized in Bacteria
    3. Synthetic Insulins have since been modfied for rapid onset bolus (e.g. Lispro) and longer-acting basal (e.g. Glargine)

IV. Mechanism

  1. See Insulin

V. Medications: Bolus Insulins (Meal-time Insulin)

  1. Precautions: Humulin R U-500 is NOT a Bolus Insulin (NOT equivalent to Bolus Insulins listed below)
    1. Humulin R U-500 is a Regular Insulin that is at 5-fold higher concentration than typical Regular Insulin
    2. At this very high concentration, Humulin R U-500 has Pharmacokinetics that are more like a mixed or Basal insulin
      1. Despite being Regular Insulin, U-500 acts more like NPH or Insulin 70/30
  2. Traditional Insulins
    1. Regular Insulin (Novolin R, Humulin R)
      1. Onset: 15 to 30 minutes
      2. Peak: 2.5 to 5 hours
      3. Duration: 6 to 8 hours
      4. Avoid in Stage IV or Stage V significant Chronic Kidney Disease
      5. Avoid if history of severe Hypoglycemia
      6. Available concentrations
        1. Humulin R U-100 (100 units/ml, orange)
        2. Humulin R U-500 (500 units/ml, green)
          1. High concentration AND basal and Bolus Insulin activity (similar to 70/30)
          2. See Basal insulins below for description
  3. Analog Insulins (Rapid, consistent absorption)
    1. Glulisine (Apidra)
      1. Onset: 5 to 15 minutes
      2. Peak: 1 to 2 hours
      3. Duration: 3 to 5 hours
      4. Similar to other bolus analogues
      5. FDA approved for chilren (age>4 years) and adults, and to take after meal
        1. Other analogs expected with same effect after meal
    2. Lispro (Humalog, Admelog)
      1. Onset: 5 to 15 minutes
      2. Peak: 1 to 2 hours
      3. Duration: 3 to 5 hours
      4. FDA approved for age >3 years
      5. Concentrations
        1. Humalog U-100 (100 units/ml) vial or KwikPen
        2. Humalog U-200 (200 units/ml) KwikPen - for patients using >20 units/day
    3. Lispro-aabc (Lyumjev)
      1. Same manufacturer as Humalog
      2. Four letter designation refers to new FDA labeling of Insulins as biologics
      3. Marketed as 10 minutes faster onset that typical Lispro Insulin
      4. Unlikely to offer any real benefit over other Lispro Insulin
      5. Concentrations
        1. Lyumjev U-100 (100 units/ml) vial or KwikPen
        2. Lyumjev U-200 (200 units/ml) KwikPen - for patients using >20 units/day
    4. Aspart (Novolog, Fiasp)
      1. FDA approved for age >2 years
      2. Onset: 5 to 15 minutes
      3. Peak: 1 to 2 hours
      4. Duration: 3 to 5 hours

VI. Dosing

  1. Precautions
    1. Humulin R U-500 is NOT a Bolus Insulin (see above)
    2. Carefully check Insulin type and concentration before dose
      1. Serious dosing errors due to concentration (100 units/ml or 200 units/ml) may occur
      2. Confirm pen or bottle formulation (Bolus Insulin or Basal insulin)
  2. Subcutaneous
    1. See Insulin Dosing
    2. See Insulin Dosing in Type I Diabetes
    3. See Insulin Dosing in Type II Diabetes
    4. See Carbohydrate Count in Insulin Dosing
    5. See Carbohydrate Counting
    6. Administer analog Insulins (e.g. Lispro) 15 min before meals, and Regular Insulin 30 min before meals
    7. Only NPH Insulin may be mixed in same syringe with bolus/rapid Insulins (draw up Bolus Insulin first)
      1. Do NOT mix other basal/Long-Acting Insulins (e.g. Glargine) with Bolus Insulins
    8. Typical daily dosing
      1. Total daily Insulin
        1. Type 1 Diabetes: 0.3 to 0.5 units/kg (up to 0.5 to 1.0 units/kg in children)
        2. Type 2 Diabetes: 1 to 1.5 units/kg
      2. Bolus Insulin dose
        1. Give 50% of total Insulin daily units as Bolus Insulin divided over 3 meals
        2. Give remaining 50% of total daily dose as Basal insulin (e.g. Insulin Glargine or Lantus)
    9. Initiating Insulin in Type 2 Diabetes
      1. Start 0.1 units/kg OR 4 units OR 10% of basal dose, given before the largest meal
      2. Titrate doses 1-2 units (or 10-15%) every 3 to 7 days
      3. Combine with Basal insulin (roughly 50% of total daily Insulin)
  3. Intravenous Regular Insulin
    1. Intravenous insulin Pharmacokinetics (other listed kinetics above is for subcutaneous dosing)
      1. Onset: Immediate
      2. Half-Life: 5-10 minutes
    2. Insulin Infusion in severe Hyperglycemia
      1. See Insulin Drip
      2. See Diabetic Ketoacidosis Management in Adults
      3. See Diabetic Ketoacidosis Management in Children
      4. See Diabetic Ketoacidosis in Pregnancy
      5. See Hyperosmolar Hyperglycemic State
      6. Do NOT start Insulin replacement until Hypokalemia is corrected
      7. Initial Insulin Bolus (optional): 0.1 units/kg Regular Insulin IV
      8. Insulin IV Infusion: Start at 0.1 units/kg/hour IV using a 1 unit/ml solution (100 units/100 ml NS)
    3. See specific conditions for emergent Insulin use outside of diabetes
      1. Acute Hyperkalemia Management
      2. Acute Pancreatitis due to severe Hypertriglyceridemia (>1000 mg/dl)
      3. Calcium Channel Overdose (or Beta Blocker Overdose)
  4. Insulin Pump
    1. FDA approved Bolus Insulins for Insulin Pump: Humalog, Novolog, Apidra, Admelog
    2. Do NOT mix Insulins in the Insulin Pump
    3. Only use an approved Bolus Insulin at standard concentration (100 units/ml)

VII. Adverse Effects

  1. See Insulin
  2. Hypoglycemia
    1. Increased risk when Hemoglobin A1C <7.4%
    2. Decreased risk with analogue Insulins
    3. Higher risk with severe Renal Insufficiency
      1. Insulin is excreted by the Kidney (30% of total)
      2. Gluconeogenesis occurs in the Kidney (30% of total)
  3. Weight gain (Excess of 4 kg over 10 years)
    1. Countered with Metformin in type 2 diabetics
    2. Countered with diet and Exercise
    3. Benefits of Glucose control outweigh weight risks
  4. Lipohypertrophy
    1. Localized fat hypertrophy and scar tissue from repeated injections in the same area
    2. Results in variable Insulin absorption as below
    3. Prevent by rotating injection sites (see below)
    4. Medical providers should examine injection sites
  5. Variable Insulin absorption
    1. Insulin absorption varies by body site
      1. Abdomen (best absorption)
      2. Arms
      3. Thigh
      4. Buttocks (least absorption)
    2. Variable absorption at lipohypertrophy sites
      1. Poor absorption causes early postprandial Hyperglycemia
      2. Depot formation causes delayed Hypoglycemia
    3. Site rotation (prevents lipohypertrophy - see above)
      1. Rotate injections within same body region
        1. Avoids Insulin absorption variability
      2. Rotate to widely different sites within region
        1. Example: Abdomen rotate to LUQ, RUQ, LLQ, RLQ

VIII. Safety

  1. Considered safe in pregnancy and Lactation

Images: Related links to external sites (from Bing)

Related Studies

Cost: Medications

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