What to do if a patient's fasting glucose levels are elevated despite taking glyburide (Glibenclamide) and Actos (Pioglitazone) and injecting 22 units of Lantus (Insulin Glargine) at bedtime and 8 units of Humalog (Insulin Lispro) three times a day (TID) with meals?

Increase Lantus and Add Prandial Insulin Coverage

Your patient requires immediate intensification: increase Lantus to 30-35 units at bedtime and add 4 units of Humalog before each meal, while discontinuing glyburide. 1, 2

Critical Issue: Overbasalization and Medication Redundancy

Your patient is experiencing a common problem called "overbasalization" - using too much basal insulin without adequate mealtime coverage, while also taking redundant medications that increase hypoglycemia risk. 1, 3

Key problems with the current regimen:

• Glyburide should be discontinued immediately when insulin therapy is initiated, as sulfonylureas cause hypoglycemia and become redundant once insulin is started 1
• At 22 units Lantus (approximately 0.3-0.4 units/kg for an average adult), the basal insulin dose is insufficient for a fasting glucose of 150 mg/dL 1, 3
• The 8 units Humalog TID suggests total daily insulin of approximately 46 units, which is likely inadequate for someone with persistent hyperglycemia 1, 2

Immediate Action Plan

Step 1: Discontinue Glyburide

• Stop glyburide immediately - it provides no additional benefit once insulin is started and increases hypoglycemia risk 1
• Continue Actos (pioglitazone) as it provides complementary insulin sensitization 1
• Ensure patient remains on metformin unless contraindicated 1

Step 2: Increase Basal Insulin Aggressively

• Increase Lantus from 22 to 30-35 units at bedtime 1, 3, 2
• Target fasting glucose: 80-130 mg/dL 1, 3
• Titration protocol: Increase by 4 units every 3 days if fasting glucose ≥180 mg/dL, or by 2 units every 3 days if fasting glucose 140-179 mg/dL 1, 3, 2
• If hypoglycemia occurs without clear cause, reduce dose by 10-20% immediately 1, 3

Step 3: Optimize Prandial Insulin

The current 8 units TID is likely insufficient. Increase to 10-12 units before each meal (or use 10% of total daily insulin dose as starting point for each meal) 1, 2

Prandial insulin titration:

• Increase each mealtime dose by 1-2 units every 3 days based on 2-hour postprandial glucose readings 1, 2
• Target postprandial glucose: <180 mg/dL 2
• Critical timing: Humalog must be given 0-15 minutes before meals, not after eating 3

Understanding the Pathophysiology

Why fasting glucose remains elevated:

• Fasting hyperglycemia reflects inadequate suppression of nocturnal hepatic glucose production 4
• Your patient's basal insulin dose of 22 units is insufficient to control overnight glucose output 1, 3
• The presence of both oral agents and insulin suggests progressive beta-cell failure requiring more aggressive insulin therapy 5

The overbasalization trap:

• When basal insulin exceeds 0.5 units/kg/day (approximately 35-50 units for most adults) without achieving targets, adding or optimizing prandial insulin becomes more important than further basal increases 1, 3, 2
• Clinical signals of overbasalization include: bedtime-to-morning glucose differential ≥50 mg/dL, hypoglycemia, and high glucose variability 1, 3

Expected Outcomes and Monitoring

Total daily insulin requirement:

• For persistent hyperglycemia with fasting glucose of 150 mg/dL, expect total daily insulin needs of 0.6-1.0 units/kg/day 2
• This translates to approximately 50-80 units total daily for an average 70-80 kg adult 2

Monitoring requirements:

• Daily fasting blood glucose monitoring during titration phase 1, 3, 2
• Pre-meal and 2-hour postprandial glucose checks to guide prandial insulin adjustments 1, 2
• Reassess A1C in 3 months 2

Alternative Consideration Before Full Basal-Bolus

Consider adding a GLP-1 receptor agonist (such as semaglutide or dulaglutide) to the basal insulin regimen before advancing to full basal-bolus therapy 1

Advantages of GLP-1 RA addition:

• Improves A1C while minimizing weight gain and hypoglycemia risk 1
• May allow lower total insulin doses 1
• Provides cardiovascular benefits if patient has established CVD 1

However, given the current fasting glucose of 150 mg/dL despite significant insulin doses, immediate intensification with prandial insulin is more appropriate than waiting for GLP-1 RA effects 1, 2

Common Pitfalls to Avoid

• Do not continue increasing Lantus beyond 40-50 units without optimizing prandial coverage - this leads to overbasalization with increased hypoglycemia risk and suboptimal control 1, 3, 2
• Do not keep glyburide - it becomes redundant and dangerous once insulin therapy is established 1
• Do not delay prandial insulin intensification - therapeutic inertia prolongs poor glycemic control and increases complication risk 1
• Avoid relying solely on correction insulin - scheduled basal-bolus regimens are superior to sliding scale approaches 2

Patient Education Essentials

• Hypoglycemia recognition and treatment - teach symptoms and always carry fast-acting carbohydrates 1, 2
• Proper injection technique and site rotation to prevent lipohypertrophy and ensure consistent absorption 2
• Timing of rapid-acting insulin: Must be given 0-15 minutes before meals for optimal postprandial control 3
• Self-monitoring blood glucose technique with clear fasting (80-130 mg/dL) and postprandial (<180 mg/dL) targets 1, 2