What are the different types of insulin?

Types of Insulin

Insulin is classified into four main categories based on onset and duration of action: rapid-acting analogs (lispro, aspart, glulisine), short-acting regular human insulin, intermediate-acting (NPH), and long-acting basal analogs (glargine, detemir, degludec), with additional premixed formulations available. 1, 2

Rapid-Acting Insulin Analogs

These are the preferred prandial insulins for controlling postprandial glucose excursions. 2

• Specific agents: Insulin lispro, insulin aspart, and insulin glulisine 1, 2
• Onset: 5-15 minutes 3, 4
• Peak: 1-2 hours 3, 4
• Duration: 3-4 hours 3, 4
• Administration timing: Immediately before meals (within 15 minutes) 2
• Clinical advantages: Superior postprandial glucose control compared to regular insulin, with reduced nocturnal and severe hypoglycemia particularly in type 1 diabetes 2, 5, 6
• Appearance: Must be clear on visual inspection—any cloudiness indicates contamination 1, 2

Newer Ultra-Rapid Formulations

• Faster-acting insulin aspart and ultra-rapid lispro provide even quicker onset than standard rapid-acting analogs, potentially reducing prandial excursions further 1
• Inhaled human insulin has rapid peak and shortened duration compared to rapid-acting analogs, may cause less hypoglycemia and weight gain, but is contraindicated in chronic lung disease (asthma, COPD) and requires mandatory spirometry testing before and after initiation 1, 2, 7

Short-Acting Insulin (Regular Human Insulin)

• Onset: 30 minutes 2
• Peak: 2-4 hours 2
• Duration: 6-8 hours 2
• Administration timing: Should be given 30-45 minutes before meals 8
• Appearance: Must be clear—any clumping, frosting, or precipitation indicates loss of potency 1, 2
• Clinical role: Less physiologic than rapid-acting analogs but remains a reasonable option when cost is a major consideration 1

Intermediate-Acting Insulin

NPH (Neutral Protamine Hagedorn) is the primary intermediate-acting formulation. 1, 2

• Onset: 2-4 hours 4
• Peak action: Present (not truly "peakless") 4
• Duration: Approximately 12-18 hours 4
• Appearance: Must appear uniformly cloudy—clear appearance indicates loss of potency 1, 2
• Dosing: Typically given once or twice daily 1
• Mixing compatibility: Can be mixed with rapid-acting analogs with only slight decrease in absorption rate but preserved postprandial glucose response 1, 2
• Clinical consideration: Higher hypoglycemia risk compared to long-acting analogs, but significantly lower cost 1

Long-Acting Basal Insulin Analogs

These provide extended duration with flatter activity profiles and are the preferred initial insulin formulation in type 2 diabetes. 1, 2

First-Generation Long-Acting Analogs

• Insulin glargine (U-100): Once-daily administration, duration approximately 24 hours 1
• Insulin detemir: Once or twice-daily administration, may have shorter duration than glargine 1, 5
• Appearance: Must be clear—cloudiness indicates contamination or degradation 2
• Critical mixing restriction: Insulin glargine cannot be mixed with other insulins due to its low pH diluent (approximately pH 4) 1, 2

Second-Generation Ultra-Long-Acting Analogs

• Insulin glargine U-300 and insulin degludec (U-100 or U-200): Once-daily administration with even flatter profiles 1
• Hypoglycemia advantage: Modestly lower absolute risk for hypoglycemia compared to NPH insulin and even U-100 glargine 1
• Clinical caveat: Cost differences are substantial while differences in hypoglycemia risk are modest and glycemic efficacy minimal compared to NPH 1

Premixed Insulin Formulations

These contain predetermined proportions of intermediate-acting insulin mixed with short- or rapid-acting insulin. 1, 2

• Common formulations: 70/30 (NPH/regular), 75/25 lispro mix, 50/50 lispro mix, 70/30 aspart mix 1, 2
• Clinical role: Reduce injection burden but offer less flexibility than basal-bolus regimens 2
• Hypoglycemia risk: Tend to have increased risk compared to basal insulin alone 1
• Pharmacodynamic limitation: Suboptimal for covering postprandial glucose excursions due to their fixed profiles 1

Concentrated Insulin Preparations

• U-500 regular insulin: Five times more concentrated than U-100, with pharmacokinetics resembling intermediate-acting insulin 2
• Clinical indication: For patients requiring high insulin doses (>200 units/day), can be administered as two or three daily injections 2
• U-200 formulations: Available for degludec and lispro, allowing smaller injection volumes 1

Critical Storage and Handling Guidelines

Proper storage is essential to maintain insulin potency. 1, 2

• Unopened vials: Must be refrigerated at 36-46°F (2-8°C), avoid temperatures <36°F or >86°F (<2°C or >30°C) 1, 2, 7
• Opened vials: May be kept at room temperature to reduce injection site irritation from cold insulin 1, 2
• Potency loss: Occurs after >1 month of use, especially at room temperature 1, 2
• Spare supply: Always maintain spare bottles of each insulin type used 1, 2
• Visual inspection before each use: Check for clumping, frosting, precipitation, or change in clarity/color 1

Insulin Mixing Guidelines

Understanding mixing compatibility is critical to avoid unpredictable insulin action. 1, 2

Safe Mixing Combinations

• Rapid-acting analogs + NPH: Can be mixed with only slight decrease in absorption rate; inject within 15 minutes before meals 1, 2
• Rapid-acting analogs + ultralente: No blunting of rapid-acting insulin onset 1
• Patients already controlled on specific mixed regimens: Should maintain their standard preparation procedure 1, 2

Contraindicated Mixing Combinations

• Short-acting (regular) + lente insulins: Not recommended except for patients already adequately controlled, due to zinc binding that delays onset of action; binding equilibrium may not be reached for 24 hours 1, 2
• Phosphate-buffered insulins (NPH) + lente insulins: Zinc phosphate may precipitate, converting longer-acting insulin to short-acting insulin unpredictably 1
• Insulin glargine + any other insulin: Absolutely contraindicated due to low pH diluent 1, 2

Critical Mixing Precautions

• No other medication or diluent should be mixed with any insulin product unless approved by the prescribing physician 1
• When mixing, always draw up rapid-acting or short-acting insulin first, then NPH 7