What are the suitable insulin options for patients with uncontrolled type 2 diabetes?

Insulin Options for Uncontrolled Type 2 Diabetes

Start with basal insulin at 10 units or 0.1-0.2 units/kg daily, using NPH, glargine, detemir, or degludec, and titrate aggressively to target fasting glucose <100 mg/dL. 1

Initial Insulin Therapy: Basal Insulin

Basal insulin is the preferred initial insulin regimen for uncontrolled type 2 diabetes, providing 24-hour coverage by suppressing hepatic glucose production between meals and overnight. 1

Basal Insulin Options:

• Intermediate-acting: NPH insulin 1
• Long-acting analogs: Insulin glargine, insulin detemir, insulin degludec 1

Long-acting analogs (glargine, detemir) cause modestly less overnight hypoglycemia than NPH and possibly slightly less weight gain with detemir, but are more expensive. 1 NPH remains a cost-effective alternative when budget is a primary concern. 1

Starting Dose and Titration:

• Begin at 10 units or 0.1-0.2 units/kg body weight daily 1
• Increase by 10-15% or 2-4 units once or twice weekly until fasting blood glucose target is met 1
• Continue metformin and possibly one additional noninsulin agent 1
• Patient self-titration algorithms improve glycemic control 1

When to Start Insulin Earlier:

If HbA1c ≥9%, consider starting dual therapy immediately (basal insulin plus metformin or another agent). 1

If glucose ≥300-350 mg/dL and/or HbA1c ≥10-12%, especially with symptoms or catabolic features, start basal insulin PLUS mealtime insulin immediately (basal-bolus regimen). 1

Advancing Beyond Basal Insulin

If basal insulin is titrated to acceptable fasting glucose (or dose >0.5 units/kg/day) but HbA1c remains above target, advance to combination injectable therapy. 1

Three Main Options for Intensification:

1. Add single injection of rapid-acting insulin analog (lispro, aspart, or glulisine) before the largest meal 1

   • Starting dose: 4 units per meal, 0.1 units/kg per meal, or 10% of basal dose per meal if HbA1c <8% 1
   • Consider decreasing basal insulin by the same amount as starting mealtime dose 1

2. Add GLP-1 receptor agonist 1

   • Associated with weight loss and less hypoglycemia 1
   • May be more poorly tolerated and expensive 1
   • FDA-approved fixed-ratio combinations: lixisenatide/glargine and liraglutide/degludec 1

3. Switch to twice-daily premixed insulin (70/30 NPH/regular, 70/30 aspart, 75/25 or 50/50 lispro) 1

   • Administered before breakfast and dinner 1
   • Requires relatively fixed meal schedule 1
   • Less costly than rapid-acting analogs but suboptimal pharmacodynamics 1

These three approaches are noninferior to each other; choice depends on patient lifestyle, cost, and tolerance. 1

Full Basal-Bolus Regimen

If single mealtime insulin injection fails to achieve HbA1c target, advance to basal-bolus with 2-3 injections of rapid-acting insulin before meals. 1

• Split total daily insulin: 50% as basal, 50% as mealtime (divided among three meals) 1
• Rapid-acting analogs (lispro, aspart, glulisine) provide better postprandial control than regular insulin 1
• Offers greater meal flexibility than premixed insulin 1

If twice-daily premixed insulin fails, advance to thrice-daily premixed insulin analogs, which are noninferior to basal-bolus regimens with similar hypoglycemia rates. 1

Adjunctive Therapy with Insulin

Continue metformin when insulin is initiated. 1

Discontinue sulfonylureas, DPP-4 inhibitors, and GLP-1 receptor agonists once complex insulin regimens (beyond basal alone) are used. 1

In patients with suboptimal control or requiring large insulin doses, adding thiazolidinediones (pioglitazone) or SGLT-2 inhibitors can improve control and reduce insulin requirements. 1 SGLT-2 inhibitors added to insulin reduce HbA1c by 0.4-0.7% and promote weight loss of 2-3 kg. 2

Specialized Insulin Products

Concentrated Insulins:

• U-500 regular insulin: For patients requiring >200 units/day 1
• U-300 glargine and U-200 degludec: Longer duration, higher doses per volume 1
• Lispro U-200: Concentrated rapid-acting option 1
• Available in prefilled pens to minimize dosing errors 1

Inhaled Insulin:

• Available for prandial use with limited dosing range 1
• Contraindicated in chronic lung disease (asthma, COPD) 1
• Not recommended for smokers or recent ex-smokers 1
• Requires spirometry before and after initiation 1

Critical Education Requirements

Comprehensive patient education is imperative, covering: 1

• Self-monitoring of blood glucose technique
• Insulin injection technique and storage
• Recognition and treatment of hypoglycemia
• "Sick day" rules
• Dietary and exercise modifications

Certified diabetes educators are invaluable when available. 1

Common Pitfalls to Avoid

• Do not delay insulin initiation in patients not achieving glycemic goals 1
• Do not undertitrate insulin—aggressive dose adjustment is essential 1
• Do not continue sulfonylureas with complex insulin regimens (increases hypoglycemia risk without benefit) 1
• Do not use inhaled insulin without spirometry screening 1
• Insulin detemir may require higher total daily doses than glargine to achieve equivalent control 1