What are the different types of insulins?

Types of Insulin

Insulins are classified into four main categories based on their onset and duration of action: rapid-acting analogs, short-acting (regular) insulin, intermediate-acting insulin, and long-acting basal insulins, with additional premixed formulations combining these components. 1

Rapid-Acting Insulin Analogs

These insulins provide the fastest onset of action and most closely mimic physiological mealtime insulin secretion:

• Insulin lispro (Humalog), insulin aspart, and insulin glulisine are the three available rapid-acting analogs 1
• Onset of action occurs within 5-15 minutes, with peak effect at approximately 1 hour and duration of approximately 4 hours 2, 3, 4
• These analogs are created by modifying the amino acid sequence of human insulin—for example, lispro reverses lysine and proline at positions B28 and B29 5, 2
• Should be administered immediately before meals (within 15 minutes) when mixed with intermediate- or long-acting insulin 1
• Provide superior postprandial glucose control compared to regular human insulin and reduce nocturnal and severe hypoglycemia, particularly in type 1 diabetes 1, 4, 6
• Faster-acting formulations of insulin aspart and lispro are now available with even more rapid pharmacokinetics 1

Short-Acting Insulin (Regular Human Insulin)

• Regular human insulin is the traditional short-acting formulation 1
• Has delayed onset (30 minutes), later peak (2-4 hours), and longer duration (6-8 hours) compared to rapid-acting analogs 2
• Must be administered 30 minutes before meals for optimal postprandial coverage 3
• Visual inspection should reveal clear solution—any clumping, frosting, or precipitation indicates loss of potency 1

Intermediate-Acting Insulin

• NPH (Neutral Protamine Hagedorn) and lente insulin are the intermediate-acting formulations 1
• Onset occurs at 2-4 hours with peak action and a tail, making NPH not truly "peakless" basal insulin 2, 4
• Should appear uniformly cloudy on visual inspection—clear appearance indicates loss of potency 1
• NPH can be mixed with rapid-acting analogs with only slight decrease in absorption rate but preserved postprandial glucose response 1
• Phosphate-buffered insulins (NPH) must never be mixed with lente insulins due to zinc phosphate precipitation 1

Long-Acting Basal Insulin Analogs

These provide extended duration with flatter activity profiles:

• Insulin glargine (U-100, U-300) and insulin detemir are first-generation basal analogs 1
• Insulin degludec is a newer ultra-long-acting analog with mean half-life of 25.4 hours and duration >42 hours 6
• Glargine is modified with glycine replacing asparagine at position A21 and two arginines added to the B-chain C-terminus, resulting in molecular weight of 6063 Da 7
• Must appear clear on visual inspection—cloudiness indicates contamination or degradation 1
• Provide better fasting glucose control and lower hypoglycemia risk compared to NPH insulin 1, 4, 6
• Insulin glargine cannot be mixed with other insulins due to its low pH diluent (pH approximately 4) 1, 7
• U-300 glargine and U-200 degludec are concentrated formulations allowing higher doses per volume with longer duration of action 1

Premixed Insulin Formulations

• Commercially available combinations include 70/30 (NPH/regular), 75/25 lispro mix, 50/50 lispro mix, and 70/30 aspart mix 1
• Contain predetermined proportions of intermediate-acting insulin mixed with short- or rapid-acting insulin 1
• Should be used when the fixed ratio matches the patient's insulin requirements 1
• Reduce injection burden but offer less flexibility than basal-bolus regimens 1
• When a specific brand is unavailable, the same formulation from another manufacturer may be substituted under medical supervision with close glucose monitoring 1, 8

Concentrated Insulin Preparations

• U-500 regular insulin is five times more concentrated than U-100, with pharmacokinetics resembling intermediate-acting insulin 1
• Can be administered as two or three daily injections for patients requiring high insulin doses 1
• U-300 glargine has longer duration than U-100 glargine but modestly lower efficacy per unit administered 1

Inhaled Insulin

• Rapid-acting inhaled human insulin is available for prandial use with rapid peak and shortened duration compared to rapid-acting analogs 1
• Contraindicated in chronic lung disease (asthma, COPD) and smoking 1
• Mandatory spirometry (FEV1) testing required before initiation and periodically thereafter due to potential decline in lung function 1
• Limited dosing range restricts use in some patients 1

Critical Storage and Handling Considerations

• Unopened vials must be refrigerated; avoid temperatures <36°F or >86°F (<2°C or >30°C) 1
• Insulin in use may be kept at room temperature to reduce injection site irritation 1
• Potency loss occurs after >1 month of use, especially at room temperature 1
• Always maintain spare bottles of each insulin type used 1

Mixing Guidelines Summary

• Rapid-acting analogs can be mixed with NPH, lente, and ultralente 1
• Short-acting and lente mixing is not recommended except for patients already controlled on such mixtures, due to zinc binding that delays onset 1
• Mixed insulins with rapid-acting components must be injected within 15 minutes before meals 1
• Patients well-controlled on specific mixed regimens should maintain their standard preparation procedure 1