How should I convert a patient on 175 units daily of premixed 70/30 insulin (70 % NPH, 30 % regular) to a regimen with 60 % basal insulin and 40 % rapid‑acting insulin using high‑concentration insulin?

Converting 70/30 Premixed Insulin to a 60/40 Basal-Prandial Split Using High-Concentration Insulin

For a patient on 175 units daily of 70/30 insulin, discontinue the premixed formulation and initiate a basal-bolus regimen with 105 units of concentrated basal insulin (U-200 or U-300) once daily plus 70 units of concentrated rapid-acting insulin (U-200 lispro) divided across three meals (approximately 23 units per meal). 1

Rationale for Abandoning 70/30 Premixed Insulin

• Premixed 70/30 insulin is explicitly contraindicated in hospitalized patients due to a 64% hypoglycemia rate versus 24% with basal-bolus therapy, and this excessive hypoglycemia risk extends to outpatient settings requiring high insulin doses. 2
• The fixed 70:30 ratio cannot be adjusted independently, creating dangerous inflexibility when a patient requires 175 units daily—far exceeding typical dosing ranges where premixed formulations are appropriate. 2
• At total daily doses approaching 1 unit/kg or higher (common in severe insulin resistance), basal-bolus regimens provide superior glycemic control with lower hypoglycemia risk compared to premixed insulin. 1

Step-by-Step Conversion Protocol

Calculate the New Basal and Prandial Doses

• Total daily dose remains 175 units to maintain continuity during transition. 1
• Basal insulin (60% of TDD): 175 × 0.60 = 105 units once daily. 1
• Prandial insulin (40% of TDD): 175 × 0.40 = 70 units total, divided as ≈23 units before each of three meals. 1

Select Appropriate Concentrated Insulin Formulations

• For basal coverage: Use U-300 glargine (Toujeo) or U-200 degludec (Tresiba) to deliver 105 units in smaller injection volumes. 1
  • U-300 glargine has a longer duration of action than U-100 glargine but modestly lower efficacy per unit, requiring close monitoring during the first week. 1
  • U-200 degludec has pharmacokinetics similar to U-100 degludec and is administered once daily. 1
• For prandial coverage: Use U-200 lispro (Humalog U-200) to reduce injection volume for the 23-unit meal doses. 1
  • U-200 lispro has pharmacokinetics identical to U-100 lispro and is administered 0–15 minutes before meals. 1
• Critical safety measure: All concentrated insulins except U-500 regular are available only in prefilled pens to minimize dosing errors; never attempt to draw concentrated insulin into standard syringes. 1

Timing and Administration

• Basal insulin: Administer 105 units of U-300 glargine or U-200 degludec once daily at the same time (typically bedtime). 1, 3
• Prandial insulin: Administer 23 units of U-200 lispro 0–15 minutes before each of the three largest meals. 1
• Never administer rapid-acting insulin at bedtime as a sole correction dose, as this markedly raises nocturnal hypoglycemia risk. 1

Titration Protocol After Conversion

Basal Insulin Adjustment

• Increase by 4 units every 3 days if fasting glucose ≥180 mg/dL. 1
• Increase by 2 units every 3 days if fasting glucose is 140–179 mg/dL. 1
• Target fasting glucose: 80–130 mg/dL. 1
• If hypoglycemia (<70 mg/dL) occurs without clear cause, reduce the basal dose by 10–20% immediately. 1

Prandial Insulin Adjustment

• Increase each meal dose by 2 units every 3 days based on 2-hour postprandial glucose readings. 1
• Target postprandial glucose: <180 mg/dL. 1
• If hypoglycemia occurs, reduce the implicated meal dose by 10–20%. 1

Critical Threshold Warning

• When basal insulin approaches 0.5–1.0 units/kg/day (approximately 60–120 units for most adults), stop further basal escalation and focus on prandial dose optimization to avoid "over-basalization." 1
• Clinical signals of over-basalization include: basal dose >0.5 units/kg/day, bedtime-to-morning glucose differential ≥50 mg/dL, hypoglycemia episodes, or high glucose variability. 1

Monitoring Requirements

• Check fasting glucose daily during the first 2–3 weeks to guide basal titration. 1
• Check glucose before each meal to calculate correction doses if needed. 1
• Obtain 2-hour postprandial glucose after each meal to assess prandial adequacy. 1
• Reassess HbA1c every 3 months during intensive titration. 1

Correction Insulin Protocol

• Add 2 units of U-200 lispro for pre-meal glucose >250 mg/dL. 1
• Add 4 units of U-200 lispro for pre-meal glucose >350 mg/dL. 1
• These correction units are in addition to the scheduled 23-unit prandial dose. 1

Foundation Therapy: Continue Metformin

• Maintain metformin at maximum tolerated dose (up to 2,000–2,550 mg daily) when converting to basal-bolus insulin. 1
• Metformin reduces total insulin requirements by 20–30% and provides superior glycemic control compared to insulin alone. 1
• Never discontinue metformin when intensifying insulin unless contraindicated (e.g., acute infection, renal impairment, tissue hypoxia). 1

Expected Clinical Outcomes

• With properly implemented basal-bolus therapy using concentrated insulins, ≈68% of patients achieve mean glucose <140 mg/dL versus ≈38% with sliding-scale or inadequate premixed regimens. 1
• HbA1c reduction of 2–3% is achievable over 3–6 months with intensive titration. 1
• Correctly executed basal-bolus regimens do not increase overall hypoglycemia incidence compared with premixed insulin when properly titrated. 1

Common Pitfalls to Avoid

• Do not convert 70/30 insulin to basal-bolus on a 1:1 basis—always recalculate the split to avoid hypoglycemia or inadequate coverage. 2, 3
• Do not use premixed insulin in patients requiring >100 units daily, as the fixed ratio becomes increasingly inappropriate at high doses. 2
• Do not delay conversion when a patient on 175 units of 70/30 has persistent hyperglycemia, as this indicates the premixed formulation is fundamentally inadequate. 1, 2
• Do not rely solely on correction insulin without adjusting scheduled basal and prandial doses; correction doses must supplement, not replace, scheduled insulin. 1
• Do not prescribe U-500 regular insulin vials without U-500 syringes, as standard U-100 syringes will cause catastrophic dosing errors. 1

Hypoglycemia Management

• Treat any glucose <70 mg/dL immediately with 15 g fast-acting carbohydrate, recheck in 15 minutes, and repeat if needed. 1
• If hypoglycemia occurs without an obvious precipitant, reduce the implicated insulin dose by 10–20% promptly. 1
• Educate the patient on hypoglycemia recognition, treatment, and the importance of carrying fast-acting carbohydrates at all times. 1