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Insulin
Aka: Insulin, Regular Insulin, NPH Insulin, Lispro, Insulin Lente, Ultralente Insulin, Novolin, Humulin, Novolog, Fiasp, Humalog, Admelog, Lispro-aabc, Lyumjev, Short-Acting Insulin, Bolus Insulin, Aspart, Apidra, Glulisine, Insulin-Related Errors, Insulin Pen
- See Also
- Insulin Dosing
- Insulin Simulation
- Glucose Metabolism
- Technique
- Injection sites: Abdomen, outer thigh, back of arm, flank and buttocks
- Insert needle at 90 degree angle into skin
- Insulin injection is subcutaneous (not intramuscular)
- Intramuscular Injection results in rapid absorption and risk of Hypoglycemia
- Prevent too deep of injection (esp. longer needles) by pinching an inch of skin at the injection site
- Hold needle in place for 5-10 seconds after injection to prevent leakage of Insulin
- Rotate injection sites to prevent lipohypertrophy (see adverse effects below)
- Preparations: Insulin Selection
- New Insulin anologues are preferred
- More consistent absorption than traditional Insulin
- Bolus analogues have more rapid onset
- Basal agents release at more constant rate
- New anologues are however 10 fold more expensive than Regular Insulin and NPH
- Very high cost results in patients stopping Insulin, resulting in hospitalization and even death
- Vials of NPH Insulin and Regular Insulin are each $26 per vial OTC at Walmart as of 2017
- Contrast with $250 per vial for analogues (e.g. Insulin Lispro, Insulin Glargine)
- Outcomes are similar with newer analogues versus older NPH Insulin and Regular Insulin
- (2015) Presc Lett 22(11):61-2
- (2019) Presc Lett 26(8): 43-4
- Combination agents are discouraged unless noncompliant
- Insulin 70/30 is also $26 OTC at Walmart as of 2017 (Reli-On)
- Reduces flexibility in meal and activity timing
- Preparations: Syringes and needles
- Needle length
- Longer needles risk deeper, intramuscular penetration, with more rapid absorption and Hypoglycemia risk
- Insulin Pen needles 4 mm are sufficiently long
- Insulin syringe needles should be at least 6 mm long to clear the syringe stopper
- Needle gauge
- Smaller needles (higher gauge) 30 or 31 are preferred for the least discomfort on insertion
- Syringe volume
- Select smallest Insulin syringe that will hold each of the Insulin doses, allowing for added coverage
- Prescribe syringes in number of boxes (100 syringes per box)
- Syringes are sized at 100 units Insulin/ml
- Insulin 30 units per 0.3 ml syringe
- Insulin 50 units per 0.5 ml syringe
- Insulin100 units per 1 ml syringe
- References
- (2014) Presc Lett 22(1): 4
- Preparations: Insulin Pens
- Supplied
- Insulin Pens are supplied in boxes of 5 pens each containing 3 ml at 100 units Insulin per ml
- Precautions
- Insulin Pens appear similar to one another despite containing different Insulins (basal or bolus)
- Read each syringe carefully (and note its color) prior to each injection to prevent Overdose errors
- Prepare cloudy Insulins (e.g. NPH) by gently rolling and inverting the pen 10 times prior to injection
- Confirm proper use by asking the patient to demonstrate preparation and injection at clinic visits
- Technique
- Attach a new needle to Insulin Pen before each use
- Prime the new needle with 2 units prior to use (removes air bubbles)
- Dial the dose
- Apply to pen to injection site, press the button, and hold in place for 5-10 seconds
- Discard the used needle
-
Drug Interactions: Diabetes Agents
- Agents safe to use with Insulin
- Metformin
- Thiazolidinediones
- Alpha-glucosidase Inhibitors
- Sitagliptin (Januvia)
- Agents safe to use with basal Insulin (Lantus, Levemir); avoid or use caution if used with Bolus Insulin (Lispro, Aspart)
- Sulfonylureas
- Glitinides
- Agents: Intravenous Regular Insulin
- Note that all other Insulins listed on this page are subcutaneous
- See Insulin Drip
- Onset: Immediate
- Half-life: 5-10 minutes
- Precautions: Insulin-Related Errors
- Insulin errors result in >100,000 emergency visits (typically Hypoglycemia related) annually in United States
- Wrong Insulin (Bolus Insulin mistakenly taken)
- Prescribers should carefully check prescriptions and home instructions for errors
- Example: Lispro prescribed instead of Lantus
- Patients should check Insulin label everytime they inject
- Bolus Insulin in vials and pen devices may be easily mistaken for basal Insulin devices
- Wrong time
- Patients must eat following Bolus Insulin (e.g. Lispro) or do not take Bolus Insulin if plan to skip the meal
- Wrong dose
- Decrease Insulin for anticipated decreased oral intake
- Assist patients with poor vision or dexterity who have difficulty drawing the correct dose
- Consider syring magnifier, pen device which click per unit, count-a-dose syringe
- Wrong technique
- Mix Insulin suspensions before use (e.g. NPH Insulin, Premixed Insulin such as Insulin 70/30)
- Roll vials or pens 10 times to mix
- Clinic staff should periodically observe patient's technique
- Obtaining fingerstick Glucose
- Calculating their Insulin dose with expected oral intake
- Drawing up Insulin dose
- Injecting Insulin
- References
- (2014) Presc Lett 21(7): 40
- Preparations: Bolus Insulins (Meal-time Insulin)
- 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)
- Indicated for those with very high Insulin requirements
- High risk for dosing errors
- Activity is similar to 70/30
- Onset in 30 minutes
- Longer duration (>12 hours) than other Bolus Insulins
- Divide dosing twice to three times daily
- Do not combine with other Insulins (i.e. basal Insulins)
- Specific U-500 syringes are available as of 2016 to reduce dosing errors
- Analogue 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 to take after meal
- Other analogues expected with same effect
- Lispro (Humalog, Admelog)
- Onset: 5 to 15 minutes
- Peak: 1 to 2 hours
- Duration: 3 to 5 hours
- 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)
- Onset: 5 to 15 minutes
- Peak: 1 to 2 hours
- Duration: 3 to 5 hours
- Preparations: Basal Insulins
- Traditional Insulins
- NPH Insulin, Novolin N, Humulin N, Humulin L (Lente)
- Onset: 1 to 2 hours
- Peak: 6 to 8 hours
- Peak time is higher risk of hypoglcemia
- Consider snack at 6 hours after dose
- Duration: 10 to 16 hours (Lente slightly longer)
- Humulin L (Lente) discontinued in U.S. in 2006
- Increased risk of Hypoglycemia (esp nocturnal) compared with newer analogues
- NPH is much less expensive than analogues (still $25/vial as of 2016 at Walmart)
- Ultralente Insulin (extended Insulin zinc suspension)
- Discontinued in U.S. in 2006
- Significant inconsistent effect even in same person
- Onset: 6-10 hours
- Peak: No peak
- Duration: 18 to 24 hours
- Analogue Insulins
- Detemir (Levemir)
- Onset: 2-4 hours
- Peak: 6-8 hours
- Duration: 12 to 20 hours (varies by dosage)
- Glargine (Lantus, Basaglar)
- Onset: 1-2 hours
- Duration: 21 to 24 hours
- Peak: No peak (flat action curve mimics continuous Insulin Infusion)
- Preparations: Combination Agents (Type II Diabetes if poor compliance)
- NPH 50/Regular 50
- NPH 70/Regular 30 (Humulin 70/30 or Novolin 70/30)
- NPL 75/Lispro 25 (Humalog Mix 75/25)
- NPH 70/Aspart 30 (Novolog Mix 70/30)
- Adverse Effects
- 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)
- Countered with Metformin in type 2 diabetics
- Countered with diet and Exercise
- Benefits of Glucose control outweigh weight risks
- 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
- Abdomen (best absorption)
- Arms
- Thigh
- Buttocks (least absorption)
- Variable absorption at lipohypertrophy sites
- Poor absorption causes early postprandial Hyperglycemia
- Depot formation causes delayed Hypoglycemia
- Site rotation (prevents lipohypertrophy - see above)
- Rotate injections within same body region
- Avoids Insulin absorption variability
- Rotate to widely different sites within region
- Example: Abdomen rotate to LUQ, RUQ, LLQ, RLQ
- Reources
- FDA Insulin storage and emergency switching
- https://www.fda.gov/Drugs/EmergencyPreparedness/ucm085213.htm
- References
- (2014) Presc Lett 21(12): 69
- Lepore (2000) Diabetes 49:2142-8 [PubMed]
- Mayfield (2004) Am Fam Physician 70(3):489-512 [PubMed]