What adjustments can be made to the treatment plan for an adult patient with type 2 diabetes mellitus (T2DM) taking Human Mixtard (insulin) 35 and 30 and metformin (glucophage) 500mg twice daily, who is experiencing hyperglycemia with post-prandial glucose levels exceeding 300mg/dL?

Immediate Insulin Intensification Required for Severe Postprandial Hyperglycemia

This patient requires immediate addition of prandial insulin coverage before meals, as postprandial glucose levels exceeding 300 mg/dL indicate both inadequate basal insulin and insufficient mealtime coverage. 1

Critical Problems with Current Regimen

Inadequate Insulin Dosing

• Human Mixtard 35 and 30 units total daily (65 units) is likely insufficient for this patient's needs, particularly given the severe postprandial hyperglycemia 1
• The current premixed insulin regimen provides suboptimal control compared to basal-bolus therapy and is associated with significantly increased hypoglycemia rates 1
• Randomized trials demonstrate that basal-bolus therapy provides better glycemic control with reduced hospital complications compared to premixed insulin regimens 1

Suboptimal Metformin Dosing

• Metformin 500 mg twice daily (1000 mg total) is below the recommended therapeutic dose 2
• The maximum effective dose is up to 2500 mg/day, with most patients requiring at least 2000 mg daily for optimal glucose control 1, 2
• Metformin should be increased to at least 1000 mg twice daily (2000 mg total) unless contraindicated 1

Recommended Treatment Plan

Step 1: Transition to Basal-Bolus Insulin Regimen

• Discontinue Human Mixtard immediately and convert to a basal-bolus regimen with long-acting basal insulin (glargine, detemir, or degludec) plus rapid-acting prandial insulin (lispro, aspart, or glulisine) 1
• Calculate total daily dose (TDD) by adding current Mixtard doses: 35 + 30 = 65 units 1
• Divide using 50:50 split: 32-33 units as basal insulin once daily, and 32-33 units as prandial insulin divided among three meals (approximately 10-11 units per meal) 1

Step 2: Aggressive Insulin Titration Protocol

• For basal insulin: Increase by 4 units every 3 days if fasting glucose ≥180 mg/dL, or by 2 units every 3 days if fasting glucose is 140-179 mg/dL, until fasting glucose reaches 80-130 mg/dL 1
• For prandial insulin: Increase by 1-2 units or 10-15% every 3 days based on 2-hour postprandial glucose readings, targeting postprandial glucose <180 mg/dL 1
• Given the severe postprandial hyperglycemia (>300 mg/dL), consider starting with higher prandial doses of 12-15 units per meal 1

Step 3: Optimize Metformin Dosing

• Increase metformin to 1000 mg twice daily (2000 mg total daily dose) immediately, unless contraindicated 1, 2
• Metformin provides complementary glucose-lowering effects, reduces total insulin requirements, and should be continued when intensifying insulin therapy 1
• If tolerated, can increase to maximum dose of 2550 mg daily in divided doses 2

Step 4: Implement Correction Insulin Protocol

• Add correction insulin using rapid-acting insulin for premeal glucose >180 mg/dL 1
• Use simplified sliding scale as adjunct: 2 units for glucose >250 mg/dL, 4 units for glucose >350 mg/dL 1
• Calculate insulin sensitivity factor (ISF) as 1500 ÷ TDD to individualize correction doses 1

Monitoring Requirements

Daily Glucose Monitoring

• Check fasting blood glucose every morning during titration phase 1
• Check pre-meal glucose before each meal to calculate correction doses 1
• Check 2-hour postprandial glucose after meals to assess adequacy of prandial insulin 1
• Target fasting glucose: 80-130 mg/dL; target postprandial glucose: <180 mg/dL 1

Clinical Reassessment Schedule

• Reassess every 3 days during active titration to adjust insulin doses 1
• Check HbA1c every 3 months during intensive titration 1
• Assess adequacy of insulin regimen at every clinical visit, looking for signs of overbasalization 1

Critical Threshold Considerations

When to Stop Escalating Basal Insulin

• When basal insulin exceeds 0.5 units/kg/day and approaches 1.0 units/kg/day, focus on intensifying prandial insulin rather than continuing to escalate basal insulin alone 1
• Clinical signals of overbasalization include: basal dose >0.5 units/kg/day, bedtime-to-morning glucose differential ≥50 mg/dL, hypoglycemia episodes, and high glucose variability 1

Alternative: Consider GLP-1 Receptor Agonist

• If patient refuses intensive insulin therapy, adding a GLP-1 receptor agonist (liraglutide or dulaglutide) to metformin provides robust glucose lowering with weight loss benefits 3
• However, at postprandial glucose levels >300 mg/dL, insulin therapy should not be delayed, as this level of hyperglycemia warrants immediate intervention 1, 3

Common Pitfalls to Avoid

Do Not Continue Premixed Insulin

• Premixed insulin regimens have unacceptably high rates of iatrogenic hypoglycemia compared to basal-bolus therapy 1
• The fixed ratio in premixed insulin cannot be adjusted to address specific fasting versus postprandial hyperglycemia 1

Do Not Delay Insulin Intensification

• Prolonged hyperglycemia at this level increases the risk of irreversible complications including blindness, kidney failure, amputations, and cardiovascular events 1, 3
• Many months of uncontrolled hyperglycemia should specifically be avoided 1

Do Not Use Sliding Scale Insulin as Monotherapy

• Sliding scale insulin treats hyperglycemia reactively after it occurs rather than preventing it, leading to dangerous glucose fluctuations 1
• All major diabetes guidelines explicitly condemn sliding scale insulin as sole treatment 1

Do Not Discontinue Metformin

• Metformin should be continued when adding or intensifying insulin therapy unless contraindicated 1
• The combination provides superior glycemic control with reduced insulin requirements and less weight gain compared to insulin alone 1

Patient Education Essentials

Hypoglycemia Recognition and Treatment

• Treat hypoglycemia immediately with 15 grams of fast-acting carbohydrate when blood glucose ≤70 mg/dL 1
• Always carry a source of fast-acting carbohydrates 1
• If hypoglycemia occurs without clear cause, reduce insulin dose by 10-20% immediately 1

Insulin Administration Technique

• Proper insulin injection technique and site rotation must be taught 1
• Rapid-acting prandial insulin should be administered 0-15 minutes before meals for optimal postprandial glucose control 1
• Never administer rapid-acting insulin at bedtime to avoid nocturnal hypoglycemia 1

Self-Monitoring Requirements

• Daily self-monitoring of blood glucose is essential during the titration phase 1
• Record all glucose values to guide dose adjustments every 3 days 1
• Learn to recognize patterns requiring insulin adjustment 1

Expected Outcomes

Glycemic Improvement

• With appropriate basal-bolus therapy at weight-based dosing, 68% of patients achieve mean blood glucose <140 mg/dL 1
• HbA1c reduction of 2-3% is achievable with proper insulin intensification 1
• No increased hypoglycemia risk when properly implemented with systematic titration 1