Diabetes: Insulin Therapy Flashcards
Pharmacologic Therapy: Treatment Options
• Type 1 diabetes
- Insulin
- Symlin (pramlintide): Rx only
• Type 2 diabetes - Oral agents: Rx only • Sulfonylureas • Non-Sulfonylurea Secretagogues • Biguanide • Thiazolidinediones • Alpha-glucosidase inhibitors • DPP-4 Inhibitors • SGLT-2 Inhibitors
- Injectables: Insulin, Pramlintide (Rx only), Exenatide, dulaglutine, semaglutide (Rx only)
- Inhaled: Insulin
Actions of Insulin
STOP: gluconeogenesis, glucogenolysis, lipolysis, ketogenesis, proteolysis
GO: glucose uptake in muscle/ad tissue, glycolysis, glycogen synthesis, protein synthesis, uptake of ions
Insulin Appearance
• Rapid-Acting: Clear / Colorless
- Lispro, Aspart, Glulisine
• Short-Acting: Clear / Colorless
- Regular
• Long-Acting: Clear / Colorless
- Glargine, Detemir, Degludec
• Intermediate-Acting: Cloudy / White
- NPH
• Combinations: Cloudy / White
- Regular, Novolog, Humalog
Rapid-Acting Insulin: Ex, DF, Pros, Cons
• Examples
- Insulin lispro (Humalog®, Admelog®)
- Insulin aspart (Novolog®, Fiasp®)
- Insulin glulisine (Apidra®)
- Rx ONLY, vials and pens
- Produced through recombinant DNA technology
- Typical dosing frequency: BID-QID, 15 minutes before a meal
• Pros
- Closely mimics endogenous postprandial insulin
- Works very fast
- More flexibility with mealtimes
- Improves postprandial hyperglycemia
- Usually less hypoglycemia than regular insulin
• Cons
- Caution with CHO intake (if < than expected = hypoglycemia)
- Cost, insurance coverage, MDI
- RX only
Short-Acting Insulin: Ex, DF, Pros, Cons
• Example
- Regular insulin (Humulin® R or Novolin® R)
- Clear & colorless
• Typical dosing frequency
- BID-QID, 30 minutes before meal
• Pros
- Relatively inexpensive
- Available OTC
- May be given IV as well
• Cons
- Takes longer to work & may cause delayed hypoglycemia
- Less flexibility with mealtimes
Intermediate-Acting Insulin: Ex, DF, Pros, Cons
• Examples
- NPH (Humulin® N, Novolin® N) (Protamine suspension slows dissolution & absorption from the injection site) (Insulin of choice for mixing)
- Typical dosing frequency: Daily (at bedtime) or BID
- Pros
- Provides basal insulin coverage
- Relatively inexpensive
- Available OTC
• Cons
- Protamine & zinc may cause immunologic reactions such as urticaria at the injection site
- Action may be unpredictable leading to hypoglycemia
Insulin Glargine (Lantus®, Basaglar®): Type, DF, Pros, Cons
Long acting insulin
• Insulin analog, 28 days stable at RT
• Typical dosing frequency:
- Insulin glargine: QD
- Must only inject in subcutaneous tissue (not IM or IV)
• Pros
- Glargine provides more predictable, steady, long acting, “peakless” basal insulin for about 24 hours.
- Decrease nocturnal hypoglycemia and less weight gain compared with NPH
• Cons
- Cost
- Injection site stinging, cannot be mixed
- pH=4 for stability
- RX Only
Insulin glargine-yfgn (Semglee®)
Long-acting insulin
- New interchangeable biosimilar
- Think generic (but not really)
- Biosimilar to Lantus only
What Is an Interchangeable Biosimilar Product?
An interchangeable product is a biosimilar that may be substituted for a reference product without the intervention of the prescribing healthcare provider, depending on state pharmacy laws.
Insulin Glargine: Mechanism of Action
- Injection of an acidic solution (pH 4.0)
- Precipitation of glargine in subcutaneous tissue (pH 7.4)
- Slow dissolution of free glargine hexamers from precipitated glargine (stabilized aggregates)
- Protracted action
Insulin Detemir (Levemir®): Type, DF, Pros, Cons
Long-acting insulin
• Insulin analog, 42 days stable at RT
• Typical dosing frequency:
- Insulin detemir: QD-BID
- Must only inject in subcutaneous tissue (not IM or IV)
• Pros
- Detemir provides more predictable, steady, long acting, “peakless” basal insulin for about 24 hours at higher doses
- Does not cause stinging (neutral pH)
- Decrease nocturnal hypoglycemia and less weight gain compared with NPH
• Cons
- Cost
- RX Only
Insulin Degludec (Tresiba®): Type, DF, Pros, Cons
Long-acting insulin • Ultra-long-acting insulin • Available as U-100 and U-200 • Insulin analog, 8 weeks stable at RT • Typical dosing frequency: Once Daily
• Pros
- Predictable, steady, long acting, “peakless” basal insulin for 42 hours.
- Does not cause stinging (neutral pH)
• Cons
- Cost
- RX Only
Concentrated Insulins
- Humalog® (lispro) U-200
- Tresiba® (degludec) U-200
- Toujeo® (glargine) U-300
- Available in insulin pens
- Similar PK to U-100
• Regular U-500
- Vial and pen
- Pros: Less volume for injection
- Cons: Cost
Inhaled Insulin
• Examples
- Insulin (Afrezza®) inhalation powder
- Produced through recombinant DNA technology
- Typical dosing frequency: BID-QID, 5 minutes before or during a meal
- Pros
- Closely mimics endogenous postprandial insulin
- Works very fast (peak in 15 minutes)
- More flexibility with mealtimes
- Improves postprandial hyperglycemia
- Less hypoglycemia than rapid insulin
- Less weight gain
• Cons
- Multiple inhalations for large doses
- Cost, insurance coverage
- RX only
- Lung disease
Afrezza Inhaled Insulin
• Afrezza is available as cartridges with
- 4 units of insulin
- 8 units of insulin
• Must use with an inhalation device called a Dreamboat
• The cartridges and inhaler should be kept at room temperature for 10 minutes prior to use
- Storage in refrigerator is recommended
Valeritas V-Go® (basal + bolus)
- 24-hour disposable wearable delivery device
- Holds 56, 66, or 76 units*
- 2.4”x1.3”x0.5”
- Offers 3 continuous preset basal rates totaling 20, 30, & 40 u/day and on-demand bolus dosing in 2 unit increments (up to 36 u/day)
Insulin Mixtures
Novolin R, Humulin R 70/30 or 50/50
- 70% NPH (50%)
- 30% Regular (50%)
Humalog R Mix 75/25
- 75% insulin lispro protamine
- 25% insulin lispro
Novolog R Mix 70/30
- 70% insulin aspart protamine
- 30% insulin aspart
Ryzodeg R 70/30
- 70% insulin degludec
- 30% insulin aspart
Initiating Insulin Therapy in Type 1 Diabetes
• Initially start total daily insulin at approximately 0.2-0.5 units/kg/day • Divide 1⁄2 daily dose as basal and 1⁄2 daily dose as bolus • Basal - NPH - Insulin glargine or insulin detemir • Bolus - Regular insulin - Rapid acting analogs • Doses vary up to 1 Unit/kg/day
Initiating Insulin Therapy in Type 2 Diabetes
• Add single dose of basal insulin - Glargine, detemir, or NPH - Usually administered at bedtime • Use conservative starting dose • 10 units (empiric) • 0.1 to 0.2 units/kg • 0.3 to 0.4 units/kg if severe hyperglycemia • Usually in combination with oral agent(s) plus lifestyle changes
Converting Insulins
• 1:1 ratio for the following insulins
- Glargine, detemir, and degludec
- Regular, lispro, aspart, and glulisine
- U-100, U-200, and U-300
Converting from NPH
• If a patient is already on NPH and you want to switch to a long acting analog:
- Add up the total daily dose of NPH
- Decrease dose by 20%
- This is your daily dose of long acting insulin
Intensive Insulin Regimens
• Goal = mimic insulin secretion of the functioning pancreas
- Basal insulin with or without insulin bolus to accommodate meals
• Individualized dosing plans
• Increased SMBG is a must
• Risks
- weight gain & hypoglycemia
• Benefits
- improved glycemic control
- delays worsening or progression of diabetes complications
Insulin Preparations
- U-100 = 100 units per 1 mL
- U-200 = 200 units per 1 mL
- U-300 = 300 units per 1 mL
- U-500 = 500 units per 1 mL
- 1 vial = 10 mL
- # units per vial: _____
- 1 pen = 3 mL
- # units per pen: _____
- Caution for travelers: Not always available worldwide
- All have pH of 7.4 except insulin glargine has pH of 4
Peak and Duration of Insulins
- Lispro/Aspart/Glulisine:
Peak 30min-2hr, Duration 3-5 hr - Regular:
Peak 2-4hr, Duration 4-8 hr - NPH:
Peak 4-10hr, Duration 10-18 - Detemir: 6-24 hr
- Degludec: 42 hr
- Glargine: 20-26
Degludec: MOA
- Insulin injected
- Phenol from the vehicle diffuses quickly and degludec links up via single side chain contacts
- Long multi-hexamer chains assemble
