What are the different types of insulin (e.g. long-acting, rapid-acting, short-acting) and how is dose titration managed in insulin therapy?

Insulin Therapy and Types of Insulin Available

For effective diabetes management, insulin therapy should be initiated with basal insulin at 10 units per day or 0.1-0.2 units/kg/day, administered once daily, while maintaining metformin therapy if not contraindicated. 1

Types of Insulin Available

Long-Acting (Basal) Insulins

• Insulin glargine (Lantus): Once-daily dosing, peakless profile, duration 24+ hours 2
• Insulin detemir (Levemir): Once or twice daily dosing, less variable absorption profile than NPH 3, 4
• Insulin degludec (Tresiba): Ultra-long acting, once daily dosing 1

Intermediate-Acting Insulins

• NPH insulin: Peak action 4-10 hours, duration 10-16 hours, more variable absorption and higher risk of hypoglycemia compared to long-acting analogs 5

Rapid-Acting Insulins

• Insulin aspart (NovoLog): Onset 10-20 minutes, peak 1-3 hours, duration 3-5 hours 6
• Insulin lispro (Humalog): Similar profile to aspart, available in U-100 and U-200 formulations 7
• Insulin glulisine (Apidra): Similar profile to other rapid-acting insulins

Short-Acting Insulins

• Regular insulin: Onset 30-60 minutes, peak 2-3 hours, duration 5-8 hours

Premixed Insulins

• NovoLog Mix 70/30: Contains 70% insulin aspart protamine (intermediate-acting) and 30% insulin aspart (rapid-acting) 6
• Humalog Mix 75/25: Contains 75% insulin lispro protamine and 25% insulin lispro
• NPH/Regular 70/30: Contains 70% NPH and 30% regular insulin

Insulin Dose Titration

Basal Insulin Initiation and Titration

1. Starting dose:

   • 10 units per day or 0.1-0.2 units/kg/day for most patients 1
   • Lower starting dose (0.1 units/kg) for elderly patients 1

2. Titration algorithm:

   • Adjust basal insulin dose every 3 days based on fasting glucose levels 1
   • Target fasting glucose: 80-130 mg/dL 1
   • If fasting glucose above target: increase by 2 units
   • For hypoglycemia: determine cause and reduce dose by 10-20% if no clear reason 1

Prandial Insulin Titration

1. When to add prandial insulin:

   • When HbA1c remains above target despite optimized basal insulin 1
   • When fasting glucose is at target but postprandial glucose remains elevated

2. Correction doses for hyperglycemia (blood glucose >180 mg/dL):

   • 150-200 mg/dL: Add 2 units rapid-acting insulin
   • 201-250 mg/dL: Add 4 units rapid-acting insulin
   • 251-300 mg/dL: Add 6 units rapid-acting insulin

   • 300 mg/dL: Add 8 units and notify provider 1

3. Prandial insulin adjustment:

   • Increase by 1-2 units or 10-15% if post-prandial glucose remains elevated 1
   • Reduce by 10-20% for hypoglycemia 1

Premixed Insulin Titration

• Starting dose: 6 units twice daily (before breakfast and before supper) 6
• Target: Pre-meal glucose of 80-110 mg/dL 6
• Titration: Weekly adjustments by -2 to +6 units per injection based on glucose readings 6

Special Considerations

Storage and Handling

• Unopened insulin should be refrigerated (36-46°F or 2-8°C) 7, 6
• In-use insulin can be kept at room temperature:
  • Vials: 28 days
  • Pens: 14 days 6
• Avoid extreme temperatures (<36°F or >86°F) and excess agitation 7
• Visually inspect insulin before use: rapid-acting and glargine should be clear, others uniformly cloudy 7

Injection Technique

• Administer subcutaneously in abdomen, thigh, buttock, or upper arm 1
• Rotate injection sites to prevent lipohypertrophy 1
• Use short needles (e.g., 4-mm pen needles) 1
• For premixed insulins like NovoLog Mix 70/30, administer within 15 minutes before meal initiation 6

Combination Therapy

• Maintain metformin when starting insulin therapy if not contraindicated 1
• Consider GLP-1 receptor agonists with basal insulin if HbA1c remains above target 1
• Fixed-ratio combination products containing basal insulin plus a GLP-1 receptor agonist are available 7

Pitfalls and Caveats

1. Hypoglycemia risk:

   • Increased risk in patients with renal impairment 1
   • Monitor more frequently with changes in physical activity, meal patterns, or during acute illness 1
   • Educate patients on hypoglycemia recognition and management 1

2. Medication errors:

   • Never share insulin pens between patients even if needle is changed 6
   • Check insulin labels before injection to prevent mix-ups 6
   • Be aware that U-40 insulin is available outside the US 7

3. Insulin mixing considerations:

   • Insulin glargine should not be mixed with other insulins due to its low pH 7
   • Rapid-acting insulin can be mixed with NPH but should be injected within 15 minutes before a meal 7

4. Weight management:

   • Insulin detemir may have a weight-sparing effect compared to other insulins 3, 5
   • Consider combination with metformin or GLP-1 receptor agonists to minimize weight gain 1

By following these guidelines for insulin therapy initiation and dose titration, while considering the specific characteristics of different insulin types, clinicians can help patients achieve optimal glycemic control while minimizing the risk of adverse effects.