How do you adjust the dose of NPH (Neutral Protamine Hagedorn) insulin in a diabetes regimen?

Adjusting NPH Insulin Dose: Evidence-Based Protocol

Initial Dosing Strategy

Start NPH insulin at 10 units per day OR 0.1-0.2 units/kg per day, administered at bedtime, and titrate by increasing 2 units every 3 days until fasting plasma glucose reaches 80-130 mg/dL without hypoglycemia. 1, 2

• Set an individualized fasting plasma glucose goal (typically 80-130 mg/dL for most adults) before beginning titration 1
• For hypoglycemia without clear cause, immediately reduce the dose by 10-20% 1, 2

Converting to Twice-Daily NPH Regimen

When A1C remains above goal despite optimized bedtime NPH, convert to a twice-daily split-dose regimen using 80% of the current bedtime dose, with 2/3 given before breakfast and 1/3 before dinner. 1, 2, 3

Conversion calculation example:

• If current bedtime NPH = 30 units
• New total daily dose = 24 units (80% of 30)
• Morning dose = 16 units (2/3 of 24)
• Evening dose = 8 units (1/3 of 24) 2

Critical pitfall to avoid:

• Never divide the dose equally between morning and evening—the 2/3:1/3 ratio accounts for greater insulin sensitivity overnight and reduces nocturnal hypoglycemia risk 2, 3
• Never maintain the same total daily dose when converting—always reduce to 80% first to prevent hypoglycemia 2, 3

Titration Protocol for Split-Dose NPH

Adjust the morning NPH dose based on the next day's fasting glucose, and adjust the evening NPH dose based on pre-dinner glucose readings, increasing by 2 units every 3 days until targets are reached. 1, 2

• The morning NPH dose primarily covers the daytime period and lunch 2
• The evening NPH dose covers dinner and provides basal insulin overnight 2
• Monitor preprandial glucose levels and bedtime glucose to evaluate regimen effectiveness 2

Adding Prandial Insulin Coverage

When converting to twice-daily NPH, add 4 units of short/rapid-acting insulin to each injection OR 10% of the reduced NPH dose for prandial coverage. 1, 3

• If A1C remains above goal with twice-daily NPH alone, add rapid-acting insulin with the largest meal or the meal causing greatest postprandial glucose excursion 1, 2
• Titrate prandial insulin by 1-2 units or 10-15% every 3 days based on postprandial glucose readings 1

Monitoring for Overbasalization

Evaluate the adequacy of NPH dosing at every visit, looking specifically for signs of overbasalization: basal dose >0.5 units/kg/day, bedtime-to-morning glucose differential ≥50 mg/dL, hypoglycemia, or high glucose variability. 1, 2

• When NPH exceeds 0.5 units/kg/day without achieving glycemic targets, adding prandial insulin is more appropriate than continuing to escalate basal insulin 1
• Monitor for the differential between evening and morning glucose—a gap ≥50 mg/dL suggests excessive basal insulin 1, 2

Frequency of Dose Adjustments

Adjust NPH doses every 3 days during active titration, not more frequently, to avoid hypoglycemia and allow adequate time to assess the effect of each change. 1, 2, 4

• Research demonstrates that glucose readings alone are sufficient to adjust insulin dosage when adjustments are made every 1-4 weeks 4
• For stable patients between clinic visits, adjustments every 1-4 weeks are appropriate and effective 4

When to Consider Alternatives to NPH

If the patient develops frequent hypoglycemia despite dose adjustments, consider switching to a long-acting basal analog (glargine or detemir) for more predictable pharmacokinetics and reduced nocturnal hypoglycemia risk. 1, 5

• Studies show glargine produces less nocturnal hypoglycemia (9.9% vs 24.0% of patients) compared to NPH while achieving similar overall glycemic control 5
• Consider morning dosing of a basal analog if the patient frequently forgets evening NPH administration 1
• If A1C remains above goal despite optimized NPH regimen, consider adding a GLP-1 receptor agonist before further insulin intensification 2

Foundation Therapy Considerations

Continue metformin (unless contraindicated) when initiating or intensifying NPH insulin therapy, as it reduces total insulin requirements and provides complementary glucose-lowering effects. 1

• Metformin should be optimized to at least 1000 mg twice daily (2000 mg total daily) if tolerated 1

Special Clinical Scenario: Steroid-Induced Hyperglycemia

For steroid-induced hyperglycemia, consider morning NPH dosing to match the typical pattern of steroid-related glucose elevation during daytime hours. 1