How should the dose of Mixtard (insulin) be divided for a patient with diabetes?

How to Divide Mixtard Insulin

For patients on Mixtard (premixed insulin), the standard approach is to give 2/3 of the total daily dose before breakfast and 1/3 before dinner, using a twice-daily injection schedule. 1

Evidence-Based Dosing Distribution

Standard 2/3 - 1/3 Split

• The American Diabetes Association recommends distributing Mixtard as approximately 67% (2/3) given before breakfast and 33% (1/3) given before dinner or at bedtime. 1
• The morning dose provides daytime basal coverage plus prandial insulin for breakfast and lunch, while the evening dose covers overnight basal needs and dinner. 1
• When converting from bedtime NPH to twice-daily Mixtard, calculate the total dose as 80% of the current bedtime NPH dose, then apply the 2/3-1/3 distribution. 1

Physiologic Rationale

• The larger morning dose addresses the higher insulin requirements during daytime hours when counter-regulatory hormones (cortisol, growth hormone) increase insulin resistance. 2
• The smaller evening dose prevents nocturnal hypoglycemia while maintaining adequate overnight glucose control. 1

Titration Strategy

Dose Adjustment Algorithm

• Adjust the morning dose based on pre-dinner and bedtime glucose readings. 1
• Adjust the evening dose based on fasting glucose readings. 1
• Increase doses by 2 units every 3 days to reach target fasting plasma glucose of 80-130 mg/dL without hypoglycemia. 1
• If hypoglycemia occurs without clear cause, reduce the corresponding dose by 10-20%. 1

Monitoring Requirements

• Check fasting glucose daily to guide evening dose adjustments. 1
• Monitor pre-dinner glucose to guide morning dose adjustments. 1
• Assess adequacy at every clinical visit, looking for patterns requiring dose redistribution. 1

Critical Thresholds and Warning Signs

When to Advance Beyond Twice-Daily Mixtard

• When total insulin dose exceeds 0.5 units/kg/day with persistent hyperglycemia, consider adding separate prandial insulin rather than continuing to escalate the premixed insulin. 1
• If A1C remains above target after optimizing the twice-daily regimen, proceed to stepwise addition of prandial insulin injections or transition to full basal-bolus therapy. 1
• Watch for overbasalization signs: bedtime-to-morning glucose differential ≥50 mg/dL, hypoglycemia, and high glucose variability. 3

Common Pitfalls to Avoid

• Do not delay dose adjustments—titrate systematically every 3 days based on glucose patterns rather than waiting weeks between changes. 1
• Do not give rapid-acting insulin at bedtime, as this significantly increases nocturnal hypoglycemia risk. 3
• Avoid continuing to escalate premixed insulin beyond 0.5 units/kg/day without addressing the need for separate prandial coverage. 1
• Continue metformin unless contraindicated, as the combination reduces total insulin requirements and provides complementary glucose-lowering effects. 3

Alternative Formulations

• Mixtard 30 (30% soluble, 70% NPH) and Mixtard 50 (50% soluble, 50% NPH) are both effective when given twice daily using the 2/3-1/3 distribution. 4, 5
• Fixed-mixture preparations provide equivalent glycemic control to "tailormade" self-mixed insulin regimens in stable patients. 4
• The choice between Mixtard 30 and Mixtard 50 depends on individual postprandial glucose patterns, with Mixtard 50 providing more rapid-acting coverage. 1

Administration Guidelines

• Inject Mixtard within 15 minutes before meals when using formulations containing rapid-acting insulin. 6
• Rotate injection sites systematically within one area (e.g., abdomen) rather than rotating to different areas with each injection to minimize absorption variability. 2
• Use the shortest needles (4-mm pen needles) as first-line choice, as they are safe, effective, and less painful. 6
• Avoid intramuscular injections, especially with premixed insulins, as severe hypoglycemia may result. 6