What is the step-wise approach to insulin management in a patient with type 2 diabetes mellitus (T2DM)?

Stepwise Insulin Management in Type 2 Diabetes

For patients with type 2 diabetes requiring insulin, begin with basal insulin (NPH, glargine, or detemir) added to existing oral agents, then advance to basal-bolus regimens or premixed insulin if glycemic targets are not achieved within 3-6 months. 1

When to Initiate Insulin Therapy

Immediate insulin initiation is mandatory in the following situations:

• Severe hyperglycemia: Random blood glucose ≥250-350 mg/dL or fasting glucose >300 mg/dL 1
• Markedly elevated HbA1c: ≥10.0-12.0% 1
• Symptomatic hyperglycemia with catabolic features (weight loss, ketonuria) 1
• Diabetic ketoacidosis or ketonuria present 1

Consider insulin therapy when:

• HbA1c ≥9.0% at diagnosis, even without symptoms 1
• Combination therapy with 2-3 oral agents fails to achieve HbA1c target after 3 months 1
• Progressive β-cell failure despite maximal oral therapy 1, 2

Step 1: Basal Insulin Initiation

Start with basal insulin while continuing metformin (discontinue sulfonylureas to reduce hypoglycemia risk). 1, 2

Basal insulin options:

• Long-acting analogs (glargine or detemir): Preferred due to less nocturnal hypoglycemia than NPH; detemir may cause less weight gain 1, 2
• NPH insulin: Less expensive alternative, dosed at bedtime or twice daily 1, 3

Initial dosing:

• Start 10 units daily at bedtime for insulin-naive patients 3
• Or 0.1-0.2 units/kg/day based on body weight 2
• If already on NPH: Switch to glargine at 80% of total NPH dose 3

Titration protocol:

• Increase by 2-3 units every 3 days until fasting glucose reaches 80-130 mg/dL 2
• Patient self-titration using algorithms improves glycemic control 1
• Target fasting plasma glucose ≤100 mg/dL 3

Step 2: Adding Prandial Insulin (Basal-Bolus Regimen)

If HbA1c remains above target after 3-6 months on optimized basal insulin, add prandial insulin to the largest meal first, then expand to other meals as needed. 1

Prandial insulin options:

• Rapid-acting analogs (lispro, aspart, glulisine): Preferred for better postprandial control, dosed just before meals 1, 2
• Regular human insulin: Less expensive but requires dosing 30 minutes before meals 1

Initial prandial dosing:

• Start with 4 units or 10% of basal dose before the largest meal 2
• Adjust by 1-2 units every 3 days based on 2-hour postprandial glucose 2
• Match prandial doses to carbohydrate intake and preprandial glucose levels 1

Basal-bolus regimen structure:

• Continue basal insulin once daily 1, 3
• Add rapid-acting insulin before each meal (3-4 injections daily total) 1
• Total daily insulin typically 0.5-1.0 units/kg/day 2

Step 3: Alternative - Premixed Insulin Regimens

For patients who prefer fewer injections or have difficulty with complex regimens, premixed insulin (70/30 or 75/25) can be used 2-3 times daily instead of basal-bolus therapy. 1

Premixed insulin dosing:

• Start with twice-daily injections before breakfast and dinner 1
• Initial dose: 0.3-0.5 units/kg/day divided between injections 2
• Provides both basal and prandial coverage in fixed ratios 1

Trade-offs:

• Less flexibility than basal-bolus regimens 1
• May cause more hypoglycemia than basal insulin alone 2
• Requires consistent meal timing and carbohydrate intake 1

Step 4: Intensive Insulin Therapy (Multiple Daily Injections)

If three-drug combination therapy including basal insulin fails to achieve HbA1c target, advance to multiple daily insulin injections (MDI) with basal plus 3 prandial doses. 1

MDI regimen components:

• Basal insulin once or twice daily (glargine once daily or detemir twice daily) 1, 3
• Rapid-acting insulin before each meal (breakfast, lunch, dinner) 1
• Correction doses for hyperglycemia using insulin sensitivity factor 2

Total daily insulin requirements:

• Typically 0.5-1.0 units/kg/day, divided as 50% basal and 50% prandial 2
• May require higher doses (>1.0 units/kg/day) in severe insulin resistance 2

Step 5: Continuous Subcutaneous Insulin Infusion (CSII/Pump)

Insulin pump therapy is an option for highly motivated patients requiring intensive insulin management, particularly those with problematic hypoglycemia or marked glucose variability. 1

Pump therapy advantages:

• Allows precise basal rate adjustments throughout the day 1
• Reduces nocturnal hypoglycemia when combined with continuous glucose monitoring 1
• Provides flexibility for irregular meal schedules 2

Combination Therapy Considerations

Continue metformin when adding insulin to reduce insulin requirements, minimize weight gain, and improve insulin sensitivity. 1, 2

Consider adding GLP-1 receptor agonists or SGLT2 inhibitors to insulin regimens in patients with cardiovascular disease or at high cardiovascular risk. 1, 4

Discontinue sulfonylureas when starting prandial insulin to avoid excessive hypoglycemia risk. 1, 2

DPP-4 inhibitors can be continued with basal insulin but provide modest additional benefit. 1

Monitoring and Adjustment

Check HbA1c every 3 months until target achieved (<7% for most patients, though individualized targets may be appropriate). 1

Self-monitoring of blood glucose is essential for:

• Fasting glucose to titrate basal insulin 3, 2
• Pre-meal and 2-hour postprandial glucose to adjust prandial insulin 1, 2
• Detecting and preventing hypoglycemia 1

Insulin dose adjustments:

• Increase basal insulin if fasting glucose >130 mg/dL 2
• Increase prandial insulin if 2-hour postprandial glucose >180 mg/dL 2
• Reduce doses if hypoglycemia occurs (glucose <70 mg/dL) 1

Critical Pitfalls to Avoid

Do not delay insulin initiation in patients with severe hyperglycemia or HbA1c ≥10%; early insulin therapy can restore β-cell function and may allow later transition to oral agents. 1

Avoid aggressive HbA1c targets (<6.5%) in patients with advanced disease, history of severe hypoglycemia, or limited life expectancy; target HbA1c 7-8% is more appropriate for these patients. 1, 2

Do not use insulin as a threat or punishment; frame it as a natural progression of disease and emphasize that it reflects β-cell decline, not patient failure. 1

Prevent hypoglycemia by reducing sulfonylureas when adding insulin, educating patients on recognition and treatment, and avoiding overly aggressive titration. 1, 2

Minimize weight gain by continuing metformin, considering GLP-1 receptor agonists, using insulin detemir over NPH or glargine, and emphasizing lifestyle modifications. 1, 2

Address insulin storage and injection technique through diabetes education; improper technique reduces efficacy and increases variability. 1