My fasting plasma glucose is 297 mg/dL while I am taking premixed insulin 30/70 (16 units in the morning and 12 units in the evening), glimepiride 4 mg daily, and metformin 1000 mg daily. How should I adjust my diabetes regimen?

Immediate Insulin Regimen Restructuring for Severe Uncontrolled Type 2 Diabetes

Your current insulin regimen is profoundly inadequate and must be restructured immediately. A fasting glucose of 297 mg/dL on premixed insulin 30/70 (16 units morning, 12 units evening) plus glimepiride 4 mg and metformin 1000 mg represents complete therapeutic failure requiring aggressive basal-bolus insulin therapy.1

Critical Problems with Current Regimen

• Premixed 70/30 insulin is contraindicated in your situation because randomized trials show a 64% hypoglycemia rate versus 24% with basal-bolus therapy, and the fixed 70:30 ratio cannot be adjusted independently to address your severe fasting hyperglycemia.1
• Your total daily insulin dose of only 28 units (16 + 12) is grossly insufficient; patients with fasting glucose ≥180 mg/dL typically require 0.3–0.5 units/kg/day as total daily insulin.1
• Glimepiride 4 mg is at maximum effective dose and provides minimal additional benefit when fasting glucose exceeds 250 mg/dL.2, 3
• Metformin 1000 mg daily is suboptimal; the maximum effective dose is 2000–2550 mg/day, and you should be on at least 2000 mg daily (1000 mg twice daily) unless contraindicated.1

Immediate Medication Changes Required

Discontinue Premixed Insulin Immediately

• Stop the 30/70 premixed insulin regimen today and transition to a scheduled basal-bolus insulin approach.1

Initiate Basal Insulin (Insulin Glargine)

• Start insulin glargine 30 units once daily at bedtime (approximately 0.3–0.5 units/kg/day for severe hyperglycemia).1, 4
• Increase by 4 units every 3 days while fasting glucose remains ≥180 mg/dL.1
• Target fasting glucose 80–130 mg/dL.1
• Stop basal escalation when dose approaches 0.5 units/kg/day (approximately 40–50 units for most adults) and add prandial insulin instead.1

Add Prandial Insulin Coverage

• Start rapid-acting insulin (lispro, aspart, or glulisine) 6 units before each of the three largest meals (18 units total prandial).1
• Administer 0–15 minutes before meals for optimal post-prandial control.1
• Increase each meal dose by 2 units every 3 days based on 2-hour post-prandial glucose readings.1
• Target post-prandial glucose <180 mg/dL.1

Optimize Metformin Dosing

• Increase metformin to 2000 mg daily (1000 mg twice daily with meals) unless contraindicated.1
• Metformin reduces total insulin requirements by 20–30% and provides superior glycemic control when combined with insulin.1
• Do not discontinue metformin when intensifying insulin therapy.1

Discontinue Glimepiride

• Stop glimepiride 4 mg immediately when initiating basal-bolus insulin to avoid additive hypoglycemia risk.1
• Sulfonylureas provide minimal additional benefit when fasting glucose exceeds 250 mg/dL and increase hypoglycemia risk when combined with intensive insulin.1, 5

Detailed Titration Protocol

Basal Insulin (Glargine) Titration

• Fasting glucose 140–179 mg/dL: increase by 2 units every 3 days.1
• Fasting glucose ≥180 mg/dL: increase by 4 units every 3 days.1
• If any glucose <70 mg/dL: reduce dose by 10–20% immediately.1
• Critical threshold: When basal insulin reaches 0.5 units/kg/day without achieving targets, stop further basal increases and intensify prandial insulin instead.1

Prandial Insulin Titration

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

Correction Insulin Protocol

• Add 2 units rapid-acting insulin for pre-meal glucose >250 mg/dL.1
• Add 4 units for pre-meal glucose >350 mg/dL.1
• Correction doses supplement—not replace—scheduled basal and prandial insulin.1

Monitoring Requirements

• Check fasting glucose daily to guide basal insulin adjustments.1
• Check pre-meal glucose before each meal to calculate correction doses.1
• Obtain 2-hour post-prandial glucose after each meal to assess prandial adequacy.1
• Minimum four glucose checks per day during intensive titration.1
• Reassess HbA1c every 3 months until stable control achieved.1

Expected Clinical Outcomes

• With properly implemented basal-bolus therapy, approximately 68% of patients achieve mean glucose <140 mg/dL, compared with 38% on inadequate regimens.1
• HbA1c reduction of 3–4% (from approximately 10–11% to 7–8%) is achievable within 3–6 months with intensive insulin titration combined with metformin.1
• Properly executed basal-bolus regimens do not increase hypoglycemia incidence compared with inadequate sliding-scale approaches.1

Critical Pitfalls to Avoid

• Never continue premixed 70/30 insulin when fasting glucose consistently exceeds 250 mg/dL; this approach is inferior and unsafe.1
• Do not delay prandial insulin addition when basal insulin alone fails to achieve target fasting glucose.1
• Never discontinue metformin when starting intensive insulin unless contraindicated, as this leads to higher insulin requirements and greater weight gain.1
• Avoid basal insulin >0.5 units/kg/day without concurrent prandial coverage, as this raises hypoglycemia risk without improving control.1
• Do not rely solely on correction (sliding-scale) insulin without scheduled basal and prandial doses; this reactive strategy is condemned by major diabetes guidelines.6, 1

Hypoglycemia Management

• Treat any glucose <70 mg/dL immediately with 15 g of fast-acting carbohydrate, recheck in 15 minutes, and repeat if needed.1
• If hypoglycemia occurs without an obvious cause, reduce the implicated insulin dose by 10–20% promptly.1
• Never give rapid-acting insulin at bedtime as a sole correction dose, as it markedly raises nocturnal hypoglycemia risk.1

Follow-Up Schedule

• 1–2 weeks post-initiation: primary-care or endocrinology visit to assess glucose control and medication tolerance.1
• Monthly visits until HbA1c falls below 9%; thereafter every 3 months.1
• Urgent endocrinology referral required for HbA1c >9% with unstable glucose patterns.1