II. Technique

  1. Injection sites: Abdomen, outer thigh, back of arm, flank and buttocks
  2. Insert needle at 90 degree angle into skin
  3. Insulin injection is subcutaneous (not intramuscular)
    1. Intramuscular Injection results in rapid absorption and risk of Hypoglycemia
    2. Prevent too deep of injection (esp. longer needles) by pinching an inch of skin at the injection site
  4. Hold needle in place for 5-10 seconds after injection to prevent leakage of Insulin
  5. Rotate injection sites to prevent lipohypertrophy (see adverse effects below)

III. Preparations: Insulin Selection

  1. New Insulin anologues are preferred
    1. More consistent absorption than traditional Insulin
    2. Bolus analogues have more rapid onset
    3. Basal agents release at more constant rate
    4. Only disadvantage is anologues double price
  2. Combination agents are discouraged unless noncompliant
    1. Reduces flexibility in meal and activity timing

IV. Preparations: Syringes and needles

  1. Needle length
    1. Longer needles risk deeper, intramuscular penetration, with more rapid absorption and Hypoglycemia risk
    2. Insulin Pen needles 4 mm are sufficiently long
    3. Insulin syringe needles should be at least 6 mm long to clear the syringe stopper
  2. Needle gauge
    1. Smaller needles (higher gauge) 30 or 31 are preferred for the least discomfort on insertion
  3. Syringe volume
    1. Select smallest Insulin syringe that will hold each of the Insulin doses, allowing for added coverage
    2. Prescribe syringes in number of boxes (100 syringes per box)
    3. Syringes are sized at 100 units Insulin/ml
      1. Insulin 30 units per 0.3 ml syringe
      2. Insulin 50 units per 0.5 ml syringe
      3. Insulin100 units per 1 ml syringe
  4. References
    1. (2014) Presc Lett 22(1): 4

V. Preparations: Insulin Pens

  1. Supplied
    1. Insulin Pens are supplied in boxes of 5 pens each containing 3 ml at 100 units Insulin per ml
  2. Precautions
    1. Insulin Pens appear similar to one another despite containing different Insulins (basal or bolus)
    2. Read each syringe carefully (and note its color) prior to each injection to prevent Overdose errors
    3. Prepare cloudy Insulins (e.g. NPH) by gently rolling and inverting the pen 10 times prior to injection
    4. Confirm proper use by asking the patient to demonstrate preparation and injection at clinic visits
  3. Technique
    1. Attach a new needle to Insulin Pen before each use
    2. Prime the new needle with 2 units prior to use (removes air bubbles)
    3. Dial the dose
    4. Apply to pen to injection site, press the button, and hold in place for 5-10 seconds
    5. Discard the used needle

VI. Drug Interactions: Diabetes Agents

  1. Agents safe to use with Insulin
    1. Metformin
    2. Thiazolidinediones
    3. Alpha-glucosidase Inhibitors
    4. Sitagliptin (Januvia)
  2. Agents safe to use with basal Insulin (Lantus, Levemir); avoid or use caution if used with bolus Insulin (Lispro, Aspart)
    1. Sulfonylureas
    2. Glitinides

VII. Agents: Intravenous Regular Insulin

  1. Note that all other Insulins listed on this page are subcutaneous
  2. See Insulin Drip
  3. Onset: Immediate
  4. Half-life: 5-10 minutes

VIII. Precautions: Insulin-Related Errors

  1. Insulin errors result in >100,000 emergency visits (typically Hypoglycemia related) annually in United States
  2. Wrong Insulin (bolus Insulin mistakenly taken)
    1. Prescribers should carefully check prescriptions and home instructions for errors (e.g. Lispro prescribed instead of Lantus)
    2. Patients should check Insulin label everytime they inject (bolus Insulin in vials and pen devices may be easily mistaken for basal Insulin devices)
  3. Wrong time
    1. Patients must eat following bolus Insulin (e.g. Lispro) or do not take bolus Insulin if plan to skip the meal
  4. Wrong dose
    1. Decrease Insulin for anticipated decreased oral intake
    2. Assist patients with poor vision or dexterity who have difficulty drawing the correct dose
      1. Consider syring magnifier, pen device which click per unit, count-a-dose syringe
  5. Wrong technique
    1. Mix Insulin suspensions before use (e.g. NPH Insulin, Premixed Insulin such as Insulin 70/30)
      1. Roll vials or pens 10 times to mix
    2. Clinic staff should periodically observe patient's technique
      1. Obtaining fingerstick Glucose
      2. Calculating their Insulin dose with expected oral intake
      3. Drawing up Insulin dose
      4. Injecting Insulin
  6. References
    1. (2014) Presc Lett 21(7): 40

IX. Agents: Bolus Insulins (Meal-time Insulin)

  1. 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
  2. Analogue 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 to take after meal
        1. Other analogues expected with same effect
    2. Lispro (Humalog)
      1. Onset: 5 to 15 minutes
      2. Peak: 1 to 2 hours
      3. Duration: 3 to 5 hours
    3. Aspart (Novolog)
      1. Onset: 5 to 15 minutes
      2. Peak: 1 to 2 hours
      3. Duration: 3 to 5 hours

X. Agents: Basal Insulins

  1. Traditional Insulins
    1. NPH Insulin, Novolin N, Humulin N, Humulin L (Lente)
      1. Onset: 1 to 2 hours
      2. Peak: 6 to 8 hours
        1. Peak time is higher risk of hypoglcemia
        2. Consider snack at 6 hours after dose
      3. Duration: 10 to 16 hours (Lente slightly longer)
      4. Humulin L (Lente) discontinued in U.S. in 2006
    2. Ultralente Insulin (extended Insulin zinc suspension)
      1. Discontinued in U.S. in 2006
      2. Significant inconsistent effect even in same person
      3. Onset: 6-10 hours
      4. Peak: No peak
      5. Duration: 18 to 24 hours
  2. Analogue Insulins
    1. Detemir (Levemir)
      1. Onset: 2-4 hours
      2. Peak: 6-8 hours
      3. Duration: 12 to 20 hours (varies by dosage)
    2. Glargine (Lantus)
      1. Onset: 1-2 hours
      2. Duration: 21 to 24 hours
      3. Peak: No peak (flat action curve mimics continuous Insulin Infusion)

XI. Combination Agents (Type II Diabetes if poor compliance)

  1. NPH 50/Regular 50
  2. NPH 70/Regular 30 (Humulin 70/30 or Novolin 70/30)
  3. NPL 75/Lispro 25 (Humalog Mix 75/25)
  4. NPH 70/Aspart 30 (Novolog Mix 70/30)

XII. Adverse Effects

  1. 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)
  2. 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
  3. 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
  4. 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

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Cost: Medications

novolin (on 1/21/2015 at Medicaid.Gov Survey of pharmacy drug pricing)
NOVOLIN 70-30 100 UNIT/ML VIAL OTC $10.71 per ml
NOVOLIN N 100 UNITS/ML VIAL OTC $10.70 per ml
NOVOLIN R 100 UNITS/ML VIAL OTC $10.66 per ml
humulin (on 11/25/2014 at Medicaid.Gov Survey of pharmacy drug pricing)
HUMULIN 70/30 KWIKPEN OTC $22.87 per ml
HUMULIN 70-30 PEN OTC $22.87 per ml
HUMULIN 70-30 VIAL OTC $10.72 per ml
HUMULIN N 100 UNITS/ML KWIKPEN OTC $22.81 per ml
HUMULIN N 100 UNITS/ML PEN OTC $22.81 per ml
HUMULIN N 100 UNITS/ML VIAL OTC $10.77 per ml
HUMULIN R 100 UNITS/ML VIAL OTC $10.73 per ml
HUMULIN R 500 UNITS/ML VIAL $53.27 per ml
novolog (on 11/18/2014 at Medicaid.Gov Survey of pharmacy drug pricing)
NOVOLOG 100 UNIT/ML CARTRIDGE $24.33 per ml
NOVOLOG 100 UNIT/ML VIAL $19.67 per ml
NOVOLOG FLEXPEN SYRINGE $25.66 per ml
NOVOLOG MIX 70-30 FLEXPEN SYRN $25.37 per ml
NOVOLOG MIX 70-30 VIAL $20.28 per ml
humalog (on 11/25/2014 at Medicaid.Gov Survey of pharmacy drug pricing)
HUMALOG 100 UNITS/ML CARTRIDGE $24.20 per ml
HUMALOG 100 UNITS/ML KWIKPEN $25.26 per ml
HUMALOG 100 UNITS/ML VIAL $19.59 per ml
HUMALOG MIX 50-50 KWIKPEN $25.00 per ml
HUMALOG MIX 50-50 VIAL $20.51 per ml
HUMALOG MIX 75-25 KWIKPEN $25.32 per ml
HUMALOG MIX 75-25 VIAL $20.39 per ml
apidra (on 1/9/2015 at Medicaid.Gov Survey of pharmacy drug pricing)
APIDRA 100 UNITS/ML VIAL $19.68 per ml
APIDRA SOLOSTAR 100 UNITS/ML $25.25 per ml

Ontology: Humulin insulin (C0020171)

Concepts Pharmacologic Substance (T121) , Hormone (T125) , Amino Acid, Peptide, or Protein (T116)
SnomedCT 350348002
English insulin, human (Humulin), insulin humulin, humulin, humulin insulin, Humulin insulin, Humulin insulin (substance)

Ontology: Insulin (C0021641)

Definition (NCI) A short-acting form of insulin. Regular insulin is obtained from animal or recombinant sources. The onset of action of regular insulin occurs at 30-90 minutes after injection; its effect lasts for 6 to 8 hours. Endogenous human insulin, a pancreatic hormone composed of two polypeptide chains, is important for the normal metabolism of carbohydrates, proteins and fats; it has anabolic effects on many types of tissues. (NCI04)
Definition (NCI) Insulin (51 aa, ~6 kDa) is encoded by the human INS gene. This protein is involved in the direct regulation of glucose metabolism.
Definition (CSP) protein hormone secreted by beta cells of the pancreas; insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose and is also an important regulator of protein and lipid metabolism; insulin is used as a drug to control insulin-dependent diabetes mellitus.
Definition (MSH) A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
Concepts Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116) , Hormone (T125)
MSH D007328
SnomedCT 325014006, 67866001, 39487003, 412222002
LNC LP70329-5, LP16325-0, LP14676-8, LP32542-0, MTHU002108, MTHU019392, LA15805-7
English Insulin, insulin, Regular Insulin, Soluble insulin, Insulin Regular, insulin preparations, insulin preparations (medication), insulin regular, Insulin [Chemical/Ingredient], insulin products, insulin preparation, insulin product, regular insulin, insulins, Insulin, Soluble, Soluble Insulin, Soluble insulin (substance), Insulin regular, Insulin, Regular, Insulin product, Insulin (substance), Insulin preparation, Insulin product (product), Regular insulin product, Unmodified insulin product, Insulin preparation, NOS, Regular insulin preparation, Unmodified insulin preparation, Insulin preparation (substance), Regular insulin (substance), Regular insulin, INSULIN
Swedish Insulin
Finnish Insuliini
French Insuline ordinaire, Insuline soluble, Insuline
Russian INSULIN, ИНСУЛИН
Spanish producto con insulina (producto), preparado insulínico, insulina (producto), producto con insulina, insulina (sustancia), insulina, preparado de insulina (producto), preparado de insulina (sustancia), preparado de insulina cristalina de cinc, preparado de insulina cristalina de zinc, preparado de insulina no modificada, preparado de insulina, insulina regular (sustancia), insulina regular, Insulina
Italian Insulina regolare, Insulina
Croatian INZULIN
Polish Insulina
Japanese インスリン, インスリン亜鉛水性懸濁液, インシュリン
Czech inzulin, insulin
Norwegian Insulin, Oppløselig insulin
German Insulin
Portuguese Insulina

Ontology: Novolin (C0028467)

Concepts Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116) , Hormone (T125)
MSH D007328
French Novolin
English novolin, NovoLIN, Novolin
Norwegian Novolin

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: 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: 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