Insulin Lispro is NOT the Same as Regular Human Insulin
Insulin lispro (Humalog) is a rapid-acting insulin analog that is structurally and pharmacologically distinct from regular human insulin, despite being nearly identical in molecular composition. 1, 2
Key Structural Difference
Insulin lispro differs from human insulin by a single amino acid transposition: the proline at position B28 and lysine at position B29 are reversed. 2, 3 This seemingly minor modification fundamentally changes how the insulin molecule behaves after injection.
Critical Pharmacokinetic Differences
The amino acid reversal prevents insulin lispro from self-associating into hexamers like regular human insulin does, resulting in dramatically different absorption and action profiles: 4, 5
- Onset of action: Insulin lispro begins working within 15 minutes, while regular insulin requires 30-60 minutes 4
- Peak action: Insulin lispro peaks at 30-90 minutes (1-3 hours), compared to 2-4 hours for regular insulin 6, 4
- Duration: Insulin lispro lasts 3-5 hours versus 6-8 hours for regular insulin 6
Clinical Implications
Insulin lispro must be injected immediately before or after meals, whereas regular human insulin requires administration 30-45 minutes before eating. 1, 5, 7 This timing difference is not interchangeable—using regular insulin timing with lispro would cause postprandial hyperglycemia, while using lispro timing with regular insulin risks severe hypoglycemia.
Pharmacists and healthcare providers should not interchange insulin types without physician approval and patient notification. 1 While both are used for prandial glucose control, they require different dosing strategies and timing protocols. 1
Regulatory Classification
Insulin lispro is classified as a rapid-acting insulin analog, not as regular (short-acting) insulin. 1 The American Diabetes Association explicitly states that rapid-acting analogs like insulin lispro are distinct therapeutic entities from regular human insulin, though both can be used in basal-bolus regimens. 6
Clinical Advantages Over Regular Insulin
Insulin lispro provides better postprandial glucose control with equal or reduced hypoglycemia risk compared to regular insulin, particularly for nocturnal episodes. 1, 3, 7 The faster onset better mimics physiological insulin secretion in response to meals. 3, 8