What are the available insulin options and their usage for a patient with diabetes in a developed country?

Available Insulin Options and Usage Guidelines

Insulin Categories by Duration of Action

In developed countries, insulin therapy is organized into four main categories based on pharmacokinetic properties, each serving distinct roles in diabetes management. 1

Rapid-Acting Insulin Analogs (Onset: 0.25-0.5 hours, Peak: 1-3 hours, Duration: 3-5 hours)

• Insulin lispro, insulin aspart, and insulin glulisine are the three primary rapid-acting analogs available, administered immediately before meals (0-15 minutes) 1, 2
• Faster-acting insulin aspart represents a newer formulation with even more rapid absorption characteristics 1
• Lispro U-200 provides concentrated dosing in half the injection volume for patients requiring large doses 1
• Inhaled insulin is available as a rapid-acting prandial option but is contraindicated in chronic lung disease and requires spirometry monitoring 1

Short-Acting Insulin (Onset: 30 minutes, Peak: 2-4 hours, Duration: 6-8 hours)

• Regular human insulin requires administration 30 minutes before meals for optimal postprandial control 1, 3
• U-500 regular insulin is five times more concentrated than U-100, has delayed onset and longer duration resembling intermediate-acting insulin, and is indicated for patients requiring more than 200 units daily 1

Intermediate-Acting Insulin (Onset: 1 hour, Peak: 6-8 hours, Duration: ~12 hours)

• NPH insulin is administered once or twice daily and represents a cost-effective alternative at approximately $25-35 per vial compared to long-acting analogs 1, 3
• NPH carries modestly higher hypoglycemia risk compared to long-acting analogs, though real-world studies show no increase in hypoglycemia-related emergency visits or hospitalizations when used with conventional treatment targets 3, 1

Long-Acting Basal Insulin Analogs (Duration: 18-42+ hours)

• Insulin glargine (U-100 and U-300) provides once-daily basal coverage with relatively peakless action 3, 1
• Insulin detemir offers once- or twice-daily dosing with modestly lower hypoglycemia risk than NPH 3, 1
• Insulin degludec (U-100 and U-200) has the longest duration of action among basal insulins 3, 1
• U-300 glargine has longer duration than U-100 glargine but modestly lower efficacy per unit administered 1

Premixed Insulin Formulations

• Human insulin premixed combinations include 70% NPH/30% regular and 50% NPH/50% regular 1, 4
• Analog premixed formulations include 75% NPL/25% insulin lispro (insulin lispro 75/25) and 70% insulin aspart protamine/30% insulin aspart (BIAsp 70/30) 1, 4
• Premixed insulins require relatively fixed meal schedules and carbohydrate content due to predetermined proportions, and carry higher hypoglycemia risk compared to basal insulin alone 3, 1

How to Use Insulin: Practical Administration Guidelines

Storage and Handling Requirements

• Unopened vials must be refrigerated at 36-46°F (2-8°C), avoiding freezing or temperatures exceeding 86°F (30°C) 1, 3
• In-use insulin may be kept at room temperature to reduce injection site irritation from cold insulin 1, 3
• Visual inspection before each use is mandatory: rapid-acting, short-acting, and glargine should appear clear, while all other types should be uniformly cloudy 3, 1
• Spare bottles of each insulin type should always be available, as loss in potency may occur after opening 3

Dose Preparation

• Verify the insulin label before each injection to avoid administering incorrect insulin 3
• For all insulin preparations except rapid-acting, short-acting, and glargine, gently roll the vial or pen in the palms to resuspend the insulin 3
• Draw air equal to the insulin dose into the syringe first and inject into the vial to avoid creating a vacuum 3
• When mixing insulins, draw clear rapid- or short-acting insulin into the syringe first, then the cloudy intermediate- or long-acting insulin 3
• Inspect for air bubbles after drawing insulin and flick the syringe to allow bubbles to escape 3

Mixing Insulin Guidelines

• Insulin glargine should not be mixed with other insulins due to the low pH of its diluent 3, 1
• Rapid-acting insulin can be mixed with NPH, lente, and ultralente 3
• When rapid-acting insulin is mixed with intermediate- or long-acting insulin, inject within 15 minutes before a meal 3
• Phosphate-buffered insulins (NPH) should not be mixed with lente insulins 3
• Currently available NPH and short-acting insulin formulations when mixed may be used immediately or stored for future use 3

Injection Procedures

• Injections are made into subcutaneous tissue of the upper arm, anterior and lateral thigh, buttocks, and abdomen (excluding a 2-inch radius around the navel) 3
• Most individuals can lightly grasp a fold of skin and inject at a 90° angle 3
• Thin individuals or children should use short needles or inject at a 45° angle to avoid intramuscular injection, especially in the thigh 3
• Embed the needle within the skin for 5 seconds after complete delivery of the insulin dose, particularly with insulin pens 3
• Routine aspiration (drawing back on the syringe) is not necessary 3

Injection Site Rotation

• Rotate injection sites within the same anatomic region rather than between different regions to maintain consistent absorption 3
• Avoid injecting into areas with lipohypertrophy or lipoatrophy as this affects insulin absorption 3

Needle Safety and Disposal

• Recapping, bending, or breaking needles increases needle-stick injury risk and should be avoided 3
• Insulin syringes, pen needles, and lancets should be disposed of in puncture-resistant containers according to local regulations 3
• Manufacturers recommend single use of disposable syringes and pen needles due to inability to guarantee sterility with reuse 3

Timing of Administration

• Rapid-acting insulin analogs: Administer 0-15 minutes before meals 1, 3
• Regular human insulin: Administer 30 minutes before meals 1, 3
• Basal insulin (NPH, detemir, glargine, degludec): Administer at the same time each day, typically once daily for long-acting analogs or once or twice daily for NPH/detemir 3, 1
• Premixed insulin: Generally administered twice daily, just before breakfast and dinner 4

Critical Clinical Considerations

Cost vs. Efficacy Trade-offs

• When comparing human insulin to analogs, cost differences are substantial while hypoglycemia risk differences are modest and glycemic efficacy differences minimal 3, 1
• Long-acting insulin analogs have modestly lower absolute risk for hypoglycemia compared with NPH but cost more 3

International Travel Considerations

• Travelers should be aware that insulin is available in U-40 strength outside the U.S., requiring syringes that match the U-40 concentration to avoid dosing errors 3

Common Pitfalls to Avoid

• Never interchange insulin species or types without prescriber approval, as changes in purity, strength, brand, type, or manufacturing method may necessitate dosage adjustments 1, 3
• No other medication or diluent should be mixed with any insulin product unless approved by the prescribing physician 3
• The method of insulin administration has greater impact on adverse effects than differences among formulations, including dose, timing of injection, and glycemic targets 3