Types of Short-Acting Insulin
Short-acting insulin refers to regular human insulin, while rapid-acting insulin analogs (insulin lispro/Humalog, insulin aspart/NovoLog, and insulin glulisine) are distinct formulations with faster onset and shorter duration of action. 1
Short-Acting Insulin: Regular Human Insulin
- Regular human insulin is the traditional short-acting formulation, requiring administration 20-45 minutes before meals 2
- Regular insulin has a slower onset and longer duration compared to rapid-acting analogs, with peak action occurring later and a prolonged tail that increases risk of late postprandial hypoglycemia 1, 3
Rapid-Acting Insulin Analogs (Distinct Category)
These are technically NOT "short-acting" but rather "rapid-acting" insulins—a separate and superior category for prandial glucose control:
Insulin Lispro (Humalog/Lyumjev)
- Onset: 5 minutes, Peak: 1-2 hours, Duration: 3-4 hours 4
- Administered within 15 minutes before meals, preferably immediately before eating 1, 4
- Created by transposing proline and lysine at positions B28 and B29 of the insulin B-chain, reducing self-association and accelerating absorption 2, 5
- Available as Humalog (traditional formulation) and Lyumjev (ultra-rapid formulation with treprostinil for even faster absorption) 5
Insulin Aspart (NovoLog/Fiasp)
- Rapid-acting analog with pharmacokinetic profile similar to insulin lispro 1, 6
- Provides faster onset and shorter duration than regular human insulin 7
- Administered immediately before meals for optimal postprandial glucose control 7
Insulin Glulisine
- Third rapid-acting analog option mentioned in guidelines 1
- Similar rapid-acting profile to lispro and aspart 1
Clinical Advantages of Rapid-Acting Analogs Over Regular Insulin
- Superior postprandial glucose control with 1- and 2-hour postprandial blood glucose levels lower than regular insulin 2
- Reduced hypoglycemia risk, particularly nocturnal and severe episodes, due to shorter duration of action 1, 2
- Greater convenience with injection immediately before meals versus 30-45 minutes prior 4, 2
- Modestly lower absolute hypoglycemia risk compared to regular human insulin, though at higher cost 1
Critical Prescribing Distinctions
- Rapid-acting analogs must be combined with basal insulin (NPH, glargine, detemir, or degludec) to provide 24-hour glucose control 4
- Discontinue sulfonylureas and meglitinides when initiating prandial insulin to prevent additive hypoglycemia 4
- Do not mix insulin glargine with other insulins due to low pH of its diluent 1
- Rapid-acting analogs can be mixed with NPH, lente, and ultralente and should be injected within 15 minutes before meals when mixed 1
Common Pitfall to Avoid
The terminology "short-acting" traditionally refers to regular human insulin, NOT the rapid-acting analogs (lispro, aspart, glulisine). 1 While both are used for prandial coverage, rapid-acting analogs have largely replaced regular insulin in clinical practice due to superior pharmacokinetics and reduced hypoglycemia risk 1, 2. When prescribing "short-acting" insulin, clarify whether regular insulin or a rapid-acting analog is intended, as timing of administration and hypoglycemia risk profiles differ significantly 4, 2.