Insulin Aspart and NPH Combination Therapy
Primary Recommendation
For patients requiring insulin therapy in non-critical care settings, use insulin aspart as prandial insulin immediately before meals combined with NPH as basal insulin, starting at a total daily dose of 0.3 units/kg/day divided equally between basal (NPH) and prandial (insulin aspart) components. 1
Dosing Algorithm
Initial Dosing Strategy
- Start with 0.3 units/kg/day total daily dose (TDD) for patients with adequate oral intake 1
- Divide the TDD equally: 50% as NPH (basal) once daily and 50% as insulin aspart (prandial) divided before meals 1
- For elderly patients or those with poor oral intake, reduce starting dose to 0.1-0.15 units/kg/day, given primarily as basal insulin 1
Timing of Administration
- Administer insulin aspart 0-5 minutes immediately before meals (breakfast, lunch, dinner) 2, 3
- Give NPH insulin once daily (typically at bedtime or morning) or twice daily if needed for better basal coverage 1, 4
- Never administer NPH at the same time as rapid-acting insulin to avoid insulin stacking 5
Evidence Supporting This Regimen
Efficacy Data
- Clinical trials demonstrate that insulin aspart plus NPH provides equivalent glycemic control to regular human insulin plus NPH, with HbA1c reductions of approximately 0.1-0.3% in both type 1 and type 2 diabetes 2, 6
- In type 1 diabetes adults (n=596), insulin aspart plus NPH achieved mean HbA1c of 7.9% with a treatment difference of -0.2% compared to regular insulin 2
- In type 2 diabetes adults (n=176), insulin aspart plus NPH resulted in similar HbA1c improvements (-0.3% vs -0.1% for regular insulin) 2
Safety Advantages
- Insulin aspart demonstrates 72% lower rate of major nocturnal hypoglycemia compared to regular human insulin (0.067 vs 0.225 events/month, p=0.001) when combined with NPH 3
- Total minor hypoglycemic events reduced by 7% with insulin aspart (p=0.048) 3
- The rapid onset and shorter duration of insulin aspart reduces hypoglycemia risk compared to regular insulin, particularly important when combined with NPH which has a peak action at 8-12 hours 1, 6, 3
Critical Warnings About NPH
Hypoglycemia Risk with Poor Oral Intake
- NPH has a pronounced peak of action 8-12 hours after injection, creating significant hypoglycemia risk in patients with poor or unpredictable oral intake 1
- Severe hypoglycemic episodes occur more frequently with NPH compared to long-acting insulin analogs (glargine, detemir) 1
- Premixed formulations containing NPH (such as 70/30 mixtures) result in threefold higher hypoglycemia rates in elderly hospitalized patients and should be avoided in hospital settings 1, 7, 8
When to Avoid NPH
- Do not use NPH in hospitalized patients, particularly elderly patients in general medicine or surgery settings 1, 7, 8
- Avoid NPH in patients with irregular meal timing or variable carbohydrate intake 8
- Consider switching to long-acting analogs (glargine, detemir) in patients experiencing recurrent nocturnal hypoglycemia despite dose adjustments 1, 4
Monitoring and Dose Adjustment
Initial Monitoring Requirements
- Increase blood glucose monitoring frequency during initiation, checking both fasting and postprandial levels 1, 8
- Target fasting glucose 90-150 mg/dL (5.0-8.3 mmol/L) 5
- Adjust NPH dose based on fasting glucose values over 1 week intervals 5
- Adjust insulin aspart doses based on pre-meal and 2-hour postprandial glucose readings 1
Titration Protocol
- If fasting glucose consistently above target: increase NPH by 2 units 5
- If experiencing hypoglycemia: decrease NPH by 2 units (or 10-20% of dose) 7, 5
- Adjust prandial insulin aspart based on carbohydrate intake and postprandial glucose patterns 1
Comparison to Alternative Regimens
NPH vs Long-Acting Analogs
- Long-acting analogs (glargine, detemir) provide more consistent basal coverage with less nocturnal hypoglycemia compared to NPH, though at higher cost 1, 4
- In type 1 diabetes, glargine plus insulin aspart resulted in lower fasting glucose (7.30 vs 8.44 mmol/L), lower HbA1c (6.87% vs 7.72%), and fewer hypoglycemic episodes (6.56 vs 8.13 episodes/patient-month) compared to once-daily NPH 4
- NPH remains a cost-effective option when used appropriately in patients with consistent meal timing and adequate monitoring 1, 6
Premixed Insulin Considerations
- Premixed insulin aspart formulations (70/30) should NOT be used in hospital settings due to threefold higher hypoglycemia risk 1, 7, 8
- Premixed formulations require consistent meal timing and are less flexible than basal-bolus regimens 7, 8
- If using premixed insulin aspart 70/30 in outpatient settings, administer twice daily (before breakfast and dinner) with 2/3 of dose in morning and 1/3 in evening 7, 8
Common Pitfalls to Avoid
Dosing Errors
- Never use the same NPH dose morning and evening if giving twice daily—morning dose should be higher 7, 8
- Do not convert from other insulin regimens on a 1:1 basis without adjusting distribution between basal and prandial components 7, 8, 5
- Avoid sliding scale insulin as the sole regimen—it results in undesirable hypoglycemia and hyperglycemia with increased hospital complications 1
Medication Management
- Continue metformin when starting insulin therapy 8, 9
- Discontinue sulfonylureas when initiating multiple-dose insulin regimens to avoid hypoglycemia 8
- Never mix NPH with insulin aspart in the same syringe 7
Patient Education Gaps
- Emphasize critical importance of consistent meal timing when using NPH, as the peak action requires food intake 8-12 hours post-injection 1, 7, 8
- Ensure patients understand recognition and treatment of hypoglycemia, particularly nocturnal hypoglycemia risk with NPH 1
- Teach proper insulin injection technique and storage requirements 1
Special Populations
Elderly Patients
- Reduce starting dose to 0.1-0.15 units/kg/day in elderly patients with reduced oral intake 1
- Consider long-acting analogs instead of NPH in elderly patients due to lower hypoglycemia risk 1
- For elderly with cognitive or functional decline, simplify regimen to fewer daily injections 5