What is the effective regimen for managing diabetes with regular human insulin (RHI) administered twice daily (BID)?

Regular Human Insulin BID Regimen for Diabetes Management

Regular human insulin (RHI) administered twice daily is a suboptimal regimen that has been largely superseded by more physiologic insulin analogs, but when used, it should be combined with intermediate-acting insulin (NPH) in a premixed formulation or as separate injections before breakfast and dinner, with the critical requirement that RHI be injected 30-45 minutes before meals to match its delayed onset of action. 1

Why Regular Human Insulin BID is Problematic

The fundamental issue with regular human insulin is its pharmacokinetic profile:

• Regular insulin has a duration of action of 6-8 hours, which increases the risk for postprandial hypoglycemia in the hours following meals 2
• In clinical practice, patients often inject regular human insulin closer to mealtime rather than the recommended 30-45 minutes before eating, causing higher postprandial glucose levels and increased potential for hypoglycemia in the postabsorptive period 1
• Rapid-acting insulin analogs (lispro, aspart, glulisine) more closely mimic physiological insulin secretion and are the preferred prandial insulin option 2

Effective BID Regimen Structure (If RHI Must Be Used)

Dosing Schedule and Timing

• Administer regular human insulin combined with NPH insulin before breakfast and before dinner 1
• Regular human insulin must be injected 30-45 minutes before meals to allow adequate absorption time 1
• This twice-daily regimen provides coverage for breakfast, lunch, and dinner, with the morning regular insulin covering breakfast and lunch, and the evening regular insulin covering dinner 1

Initial Dosing Strategy

For patients requiring insulin therapy:

• Start with a total daily insulin dose of 0.3-0.5 units/kg/day for patients with type 2 diabetes and significant hyperglycemia, divided between the two injections 3
• For insulin-naive patients with type 2 diabetes and mild-to-moderate hyperglycemia, begin with 10 units or 0.1-0.2 units/kg/day, split between morning and evening doses 3
• Typically use a 30/70 premixed formulation (30% regular/70% NPH) or mix the insulins separately in similar proportions 1, 4

Dose Distribution

• Give approximately 60-70% of the total daily dose in the morning and 30-40% in the evening 1
• The morning NPH component provides basal coverage through the day, while the evening NPH provides overnight basal coverage 1

Titration Algorithm

• Increase the total daily dose by 2-4 units every 3 days based on fasting and pre-dinner glucose values 3
• If fasting glucose is 140-179 mg/dL, increase the evening dose by 2 units every 3 days 3
• If fasting glucose is ≥180 mg/dL, increase the evening dose by 4 units every 3 days 3
• Target fasting plasma glucose of 80-130 mg/dL 3
• If hypoglycemia occurs, reduce the dose by 10-20% immediately 3

Critical Limitations and When to Advance Therapy

Inadequate Coverage Patterns

• A twice-daily regular insulin regimen is suboptimal for controlling post-lunch and/or pre-dinner hyperglycemia in many patients 5
• When basal insulin requirements exceed 0.5 units/kg/day and glycemic targets are not met, transition to a basal-bolus regimen with rapid-acting analogs rather than continuing to escalate the BID regimen 3

Superior Alternative: Basal-Bolus with Analogs

• Basal insulin (glargine or detemir) once or twice daily combined with rapid-acting insulin analogs (lispro, aspart, glulisine) before each meal provides superior postprandial control 2, 1
• Rapid-acting analogs can be injected immediately before meals (0-15 minutes), offering greater flexibility and better matching of insulin action to carbohydrate absorption 2, 1
• Long-acting insulin analogs have no pronounced concentration peak and reduce nocturnal hypoglycemia risk compared to NPH insulin 2

Alternative: Three Times Daily Premixed

• For patients requiring intensification beyond BID but not ready for full basal-bolus, consider premixed insulin three times daily (before each meal) 5, 4
• Three daily injections of premixed insulin (such as 30/70 or Mix50) maintain glucose control more effectively than twice-daily administration, particularly for post-lunch hyperglycemia 5, 4

Monitoring Requirements

• Daily fasting blood glucose monitoring is essential during titration 3
• Perform seven-point blood glucose profiles (pre-meals, 2-hour post-meals, bedtime) to assess adequacy of coverage throughout the day 1
• Check HbA1c every 3 months during active titration 3

Common Pitfalls to Avoid

• Do not allow patients to inject regular insulin at mealtime—this defeats the purpose and causes postprandial hyperglycemia followed by late hypoglycemia 1
• Do not continue escalating a BID regimen when post-lunch or pre-dinner glucose remains elevated—this indicates need for three times daily or basal-bolus therapy 5
• Do not use regular human insulin when rapid-acting analogs are available—the analogs provide superior postprandial control with lower hypoglycemia risk 2, 1
• Do not rely solely on sliding-scale correction insulin—scheduled insulin regimens with basal and prandial components are strongly preferred 6

Foundation Therapy

• Continue metformin unless contraindicated when initiating or intensifying insulin therapy 3
• Metformin reduces total insulin requirements and provides complementary glucose-lowering effects 3

Inpatient Considerations

• In hospitalized patients, scheduled subcutaneous insulin injections should align with meals, using a basal-bolus regimen rather than BID regular insulin 6
• The sole use of sliding-scale insulin in the inpatient hospital setting is strongly discouraged 6
• For hospitalized patients requiring insulin, use a total daily dose of 0.3-0.5 units/kg with half as basal insulin, not a BID regular insulin regimen 7