Comparison of Insulin Glargine, NPH, and Regular Human Insulin
For patients with diabetes requiring insulin therapy, insulin glargine offers superior nocturnal hypoglycemia safety compared to NPH insulin, while regular human insulin serves a fundamentally different role as prandial coverage rather than basal insulin. These three insulins cannot be directly compared as therapeutic equivalents because they serve different physiological purposes in diabetes management. 1
Comparative Table
| Characteristic | Insulin Glargine (Long-Acting Basal) | NPH Insulin (Intermediate-Acting Basal) | Regular Human Insulin (Short-Acting Prandial) |
|---|---|---|---|
| Onset of Action | 1-2 hours [2,3] | 1-2 hours [1] | 30-60 minutes [1] |
| Peak Activity | No pronounced peak (peakless profile) [1,3] | 4-6 hours after administration [1,4] | 2-4 hours [1] |
| Duration of Action | Up to 24 hours [1,3] | 12-18 hours (often requires twice-daily dosing) [1] | 6-8 hours [1] |
| Dosing Frequency | Once daily (typically at bedtime) [1,2] | Once or twice daily [1] | Before each meal (3-4 times daily) [1] |
| Primary Clinical Role | Basal insulin coverage (suppresses hepatic glucose production overnight and between meals) [1,2] | Basal insulin coverage [1] | Prandial (mealtime) insulin coverage [1] |
| Pharmacokinetic Profile | Flat, constant plasma concentration with no peak [1,3] | Variable absorption with pronounced peak [1] | Rapid rise and fall corresponding to meal absorption [1] |
| Hypoglycemia Risk (Overall) | Similar to or lower than NPH [1,3,5] | Moderate to high (especially with twice-daily dosing) [1] | High when used without adequate carbohydrate intake [1] |
| Nocturnal Hypoglycemia Risk | Significantly lower than NPH [1,3,6] | Higher due to peak activity 4-6 hours post-dose [1,4] | Not applicable (not used for overnight coverage) [1] |
| Glycemic Control (A1C Reduction) | Comparable to NPH (similar efficacy) [1,7,3] | Comparable to glargine [1,7] | Used for postprandial control, not A1C comparison [1] |
| Weight Gain | Similar to NPH [1] | Similar to glargine [1] | Associated with weight gain when used intensively [1] |
| Mixing with Other Insulins | Cannot be mixed (due to acidic pH) [2,5] | Can be mixed with regular insulin [1] | Can be mixed with NPH [1] |
| Cost Considerations | More expensive than NPH; biosimilar/follow-on products available [1] | Significantly less expensive; available at select pharmacies for ~$25/vial [1] | Significantly less expensive; available at select pharmacies for ~$25/vial [1] |
| Injection Site Reactions | Similar to NPH [7,3] | Similar to glargine [7] | Similar to other insulins [1] |
| Clinical Trial Evidence | Demonstrated in DCCT follow-up; reduced microvascular/macrovascular complications with intensive therapy [1] | Demonstrated in DCCT; 50% reduction in microvascular complications with intensive control [1] | Used in landmark DCCT trial demonstrating benefits of intensive therapy [1] |
Critical Clinical Context
When to Choose Each Insulin
Insulin glargine is preferred when:
- Nocturnal hypoglycemia is problematic or high-risk (elderly, renal impairment, hypoglycemia unawareness) 1, 2
- Once-daily basal insulin dosing is desired for adherence 1, 2
- More predictable basal insulin coverage is needed 1, 3, 6
- Cost is not the primary barrier to therapy 1
NPH insulin remains appropriate when:
- Cost is a significant concern (individuals with relaxed A1C goals, low hypoglycemia rates, prominent insulin resistance) 1
- Patient has normal renal function and low hypoglycemia risk 1
- Twice-daily dosing is acceptable to the patient 1
- Mixing with regular insulin in the same syringe is desired 1
Regular human insulin is indicated when:
- Prandial (mealtime) insulin coverage is required 1
- Used in combination with basal insulin (glargine or NPH) in basal-bolus regimens 1, 7
- Cost considerations favor human insulin over rapid-acting analogs 1
- Patient is hospitalized and requires sliding-scale or correction insulin 1
Common Pitfalls to Avoid
Do not use regular human insulin as basal insulin replacement - its short duration of action (6-8 hours) cannot provide adequate 24-hour basal coverage, leading to periods of hyperglycemia and increased risk of diabetic ketoacidosis in type 1 diabetes. 1
Do not mix insulin glargine with any other insulin - its acidic pH formulation precipitates when mixed, destroying its peakless pharmacokinetic profile and potentially causing unpredictable absorption. 2, 5
Do not assume equivalent dosing when switching between glargine and NPH - while total daily doses are often similar, the distribution and timing differ significantly; patients switching from twice-daily NPH to once-daily glargine typically use 80-100% of their total NPH dose. 7
Recognize that cost differences are substantial - human insulins (NPH and regular) can be purchased for approximately $25/vial at select pharmacies, while insulin glargine costs significantly more ($165-$340 per 1,000 units depending on formulation), making NPH and regular insulin the appropriate choice for many patients with type 2 diabetes when cost is a barrier. 1
Evidence Quality Considerations
The comparison between insulin glargine and NPH insulin is supported by multiple high-quality randomized controlled trials in both type 1 and type 2 diabetes, consistently demonstrating similar glycemic control with reduced nocturnal hypoglycemia for glargine. 1, 7, 3 However, the American Diabetes Association acknowledges that these hypoglycemia advantages may be modest and may not persist in real-world practice settings. 1
The landmark DCCT trial, which established the benefits of intensive insulin therapy, was conducted using regular human insulin and NPH insulin, demonstrating that excellent outcomes are achievable with human insulins when used appropriately. 1