How to manage a patient with uncontrolled hyperglycemia on Mixtard (biphasic insulin) 22 and 16?

Management of Uncontrolled Hyperglycemia on Mixtard 22/16

Your patient on Mixtard 22 units morning and 16 units evening with uncontrolled hyperglycemia requires immediate transition to a basal-bolus insulin regimen, as premixed insulins have unacceptably high rates of hypoglycemia and inferior glycemic control compared to modern basal-bolus therapy. 1, 2

Immediate Regimen Change Required

Discontinue the premixed insulin (Mixtard) and transition to basal-bolus therapy immediately. 1, 2

• Calculate total daily dose (TDD): 22 + 16 = 38 units currently 3
• Split as 50% basal insulin (19 units of insulin glargine once daily) and 50% prandial insulin (approximately 6 units of rapid-acting insulin before each of three meals) 3, 2
• Randomized trials demonstrate that basal-bolus therapy provides superior glycemic control with reduced hospital complications compared to premixed insulin regimens 2

Aggressive Titration Protocol

Titrate basal insulin aggressively based on fasting glucose:

• If fasting glucose ≥180 mg/dL: increase basal insulin by 4 units every 3 days 3, 2
• If fasting glucose 140-179 mg/dL: increase by 2 units every 3 days 3, 2
• Target fasting glucose: 80-130 mg/dL 1, 3

Titrate prandial insulin based on postprandial readings:

• Increase by 1-2 units or 10-15% every 3 days based on 2-hour postprandial glucose readings 2
• Target postprandial glucose <180 mg/dL 1, 3

Critical Threshold to Recognize

When basal insulin exceeds 0.5 units/kg/day, prioritize intensifying prandial insulin rather than continuing to escalate basal insulin alone. 3, 2

• Clinical signs of "overbasalization" include: bedtime-to-morning glucose differential ≥50 mg/dL, hypoglycemia, and high glucose variability 2
• At this threshold, add or increase prandial insulin coverage before meals causing greatest glucose excursions 3, 2

Foundation Therapy Optimization

Continue or initiate metformin unless contraindicated (renal dysfunction, metabolic acidosis). 3, 2

• Metformin combined with insulin reduces weight gain, lowers insulin requirements, and decreases hypoglycemia risk 4
• Target dose: at least 1000 mg twice daily (2000 mg total), up to 2500 mg/day maximum 3

Patient Education Essentials

Provide immediate education on:

• Self-monitoring of blood glucose before meals and at bedtime until control achieved 5
• Recognition and treatment of hypoglycemia: 15-20 grams of rapid-acting glucose, recheck in 15 minutes 5, 3
• Proper insulin injection technique and site rotation to prevent lipohypertrophy 2, 4
• "Sick day" management rules: never stop insulin, check glucose more frequently during illness 3

Monitoring Requirements

Daily fasting blood glucose monitoring is essential during titration. 3, 2

• Check HbA1c every 3 months during intensive titration 3
• Assess adequacy of insulin dose at every clinical visit 2
• If any blood glucose <70 mg/dL occurs, reduce the relevant insulin component by 10-20% immediately 1, 3

Common Pitfalls to Avoid

Do not continue premixed insulin in patients with uncontrolled hyperglycemia. 2, 4

• Premixed insulins have significantly increased hypoglycemia rates and are not recommended for hospital or intensive management settings 1, 2
• Do not delay transition to basal-bolus therapy, as months of uncontrolled hyperglycemia increase long-term complication risk 3
• Do not rely solely on correction (sliding scale) insulin without scheduled basal and prandial components 1

Alternative Consideration

If the patient is unwilling or unable to perform multiple daily injections, consider adding a GLP-1 receptor agonist to basal insulin. 3, 2

• This combination provides potent glucose-lowering with less weight gain and hypoglycemia than intensified insulin regimens 3, 2
• However, this approach still requires discontinuation of the premixed insulin 2