What is the recommended approach for insulin treatment in patients with diabetes?

Insulin Treatment in Diabetes: A Comprehensive Guide

Initial Insulin Initiation

For patients with type 2 diabetes requiring insulin therapy, start with basal insulin at 10 units once daily or 0.1-0.2 units/kg body weight, administered at the same time each day, and titrate by 2-4 units every 3 days until fasting blood glucose reaches 80-130 mg/dL. 1, 2, 3

When to Start Insulin

• Type 2 Diabetes: Initiate basal insulin when HbA1c remains >7% despite optimal oral medications (metformin plus additional agents) 1, 2
• Severe Hyperglycemia: Start immediately when HbA1c ≥9%, blood glucose ≥300-350 mg/dL, or when patients have symptomatic/catabolic features 1, 2
• Type 1 Diabetes: Insulin is required at diagnosis, with total daily dose typically 0.4-1.0 units/kg/day (0.5 units/kg/day for metabolically stable patients), split approximately 50% basal and 50% prandial 1, 2

Specific Starting Doses by Clinical Scenario

Insulin-naive type 2 diabetes patients: 10 units once daily or 0.1-0.2 units/kg/day 2, 3

Severe hyperglycemia (HbA1c ≥9% or glucose ≥300 mg/dL): Consider higher starting doses of 0.3-0.4 units/kg/day 2

Hospitalized patients (insulin-naive or low-dose): 0.3-0.5 units/kg total daily dose, with half as basal insulin 2

High-risk patients (elderly >65 years, renal failure, poor oral intake): Lower doses of 0.1-0.25 units/kg/day 2

Basal Insulin Titration Algorithm

Increase basal insulin 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 reaching target of 80-130 mg/dL. 2

Titration Guidelines

• Monitor fasting blood glucose daily during titration 2, 4
• If fasting glucose <80 mg/dL on more than 2 occasions per week, decrease dose by 2 units 2
• If hypoglycemia occurs (glucose <70 mg/dL), determine the cause and reduce dose by 10-20% 1, 2
• Most patients can self-titrate by adding 1-2 units (or 5-10% for higher doses) once or twice weekly 2

When to Add Prandial Insulin

Add prandial insulin when basal insulin exceeds 0.5 units/kg/day and HbA1c remains above target despite fasting glucose reaching 80-130 mg/dL, or after 3-6 months of basal insulin optimization without achieving HbA1c goals. 1, 2

Critical Warning: Overbasalization

Continuing to escalate basal insulin beyond 0.5-1.0 units/kg/day without addressing postprandial hyperglycemia leads to suboptimal control and increased hypoglycemia risk 2. Clinical signals of overbasalization include:

• Basal dose >0.5 units/kg/day 2
• High bedtime-to-morning glucose differential (≥50 mg/dL) 2
• Hypoglycemia episodes 2
• High glucose variability 2

Adding Prandial Insulin: Step-by-Step

1. Start with one meal: Add 4 units of rapid-acting insulin before the largest meal or the meal causing greatest postprandial glucose excursion (alternatively, use 10% of current basal dose) 1, 2, 4

2. Titrate prandial dose: Increase by 1-2 units or 10-15% every 3 days based on pre-meal and 2-hour postprandial glucose readings 2, 4

3. Add to additional meals: If postprandial glucose remains >180 mg/dL at other meals, add prandial insulin to those meals sequentially 5

4. Full basal-bolus regimen: Eventually advance to 3 pre-meal injections of rapid-acting insulin if needed 1, 5

Insulin Types and Administration

Basal Insulin Options

Long-acting analogs (insulin glargine, detemir, degludec): Provide 24-hour coverage with flatter profiles and less nocturnal hypoglycemia compared to NPH 1, 6

NPH insulin: Less costly alternative but with more pronounced peak and higher nocturnal hypoglycemia risk 1, 6

Prandial Insulin Options

Rapid-acting analogs (lispro, aspart, glulisine): Administer 0-15 minutes before meals; provide better postprandial control than regular insulin 1, 7

Regular human insulin: Less costly but requires administration 30 minutes before meals with longer duration of action 1, 4

Faster-acting formulations (faster aspart): Newer ultrafast-acting options that more closely mimic physiologic insulin secretion 7

Administration Guidelines

• Timing: Administer basal insulin at the same time each day; rapid-acting insulin 0-15 minutes before meals 1, 4, 3
• Injection sites: Rotate between abdominal area, thigh, and deltoid within the same region to prevent lipodystrophy 3
• Do not mix: Insulin glargine should not be diluted or mixed with other insulins due to its low pH 2, 4, 3
• Route: Subcutaneous only; do not administer intravenously or via insulin pump 3

Hospital Insulin Management

Critical Care Setting

Use continuous intravenous insulin infusion based on validated protocols, with blood glucose monitoring every 30 minutes to 2 hours. 1

Non-Critical Care Setting

Scheduled subcutaneous insulin with basal, nutritional, and correction components (basal-bolus regimen) is preferred for patients with good nutritional intake. 1

• Patients eating: Monitor glucose before meals 1
• Patients NPO or poor intake: Basal plus correction insulin regimen; monitor every 4-6 hours 1
• Avoid sliding scale insulin alone: This is strongly discouraged as the sole method of treatment 1, 4

Hospitalized Patient Dosing

• Insulin-naive or low-dose patients: 0.3-0.5 units/kg total daily dose, half as basal 2
• High-dose home insulin (≥0.6 units/kg/day): Reduce total daily dose by 20% to prevent hypoglycemia 2
• Premeal glucose targets: Generally <140 mg/dL 1
• Random glucose targets: <180 mg/dL 1

Combination Therapy Strategies

Continuing Oral Medications

Metformin should be continued when initiating or intensifying insulin therapy unless contraindicated, as it reduces weight gain, lowers insulin requirements, and decreases hypoglycemia. 1, 2

• Sulfonylureas, DPP-4 inhibitors, and GLP-1 receptor agonists may be continued with basal insulin 1
• These agents are typically discontinued if advancing to basal-bolus or multiple-dose premixed insulin regimens 1
• SGLT-2 inhibitors or thiazolidinediones may improve control and reduce insulin requirements in patients requiring large doses 1

Alternative Intensification Options

If basal insulin alone is insufficient:

1. Basal + single prandial injection: Add rapid-acting insulin before largest meal 1
2. Basal + GLP-1 receptor agonist: Associated with weight loss and less hypoglycemia but more expensive 1
3. Twice-daily premixed insulin: 70/30 NPH/regular or analog mixes before breakfast and dinner 1

These approaches have shown noninferiority to each other in clinical trials 1

Switching Between Insulin Regimens

From Other Insulins to Insulin Glargine

• From once-daily TOUJEO (U-300): Start glargine U-100 at 80% of TOUJEO dose 3
• From once-daily NPH: Start glargine at same dose as NPH 3
• From twice-daily NPH: Start glargine at 80% of total NPH dose 3

Increase blood glucose monitoring frequency during and for several weeks after any insulin regimen change. 3

Hypoglycemia Prevention and Management

Prevention Strategies

• Establish a hypoglycemia management protocol for each patient 1
• Review and modify regimen when glucose <70 mg/dL is documented 1
• Reduce dose by 10-20% if hypoglycemia occurs after determining the cause 1, 2
• Avoid inappropriate timing of short/rapid-acting insulin in relation to meals 1
• Monitor closely when changing injection sites from lipodystrophic areas to normal tissue 3

High-Risk Situations

Patients at increased risk include those with:

• Altered nutritional state 1
• Renal or liver disease 1
• Sudden reduction in corticosteroid dose 1
• Reduced oral intake or new NPO status 1
• Interruption of enteral/parenteral nutrition 1

Special Populations

Type 1 Diabetes

• Basal insulin alone is insufficient: Must use concomitantly with short-acting insulin 3
• Starting dose: Approximately one-third of total daily insulin as basal, with remainder as prandial 3
• Never dose based solely on premeal glucose: This ignores basal requirements and caloric intake, increasing hypoglycemia and hyperglycemia risk 1

Youth with Type 2 Diabetes

• Start basal insulin when HbA1c >8.5% without acidosis/ketosis at 0.5 units/kg/day in addition to metformin 2
• Target HbA1c <6.5% for youth 2

Elderly and High-Risk Patients

• Use lower starting doses (0.1-0.25 units/kg/day) 2
• Consider simplifying regimens for those with limited self-management abilities 4
• For prandial insulin ≤10 units/dose, consider discontinuing and adding non-insulin agents 4

Patient Education Requirements

Essential education topics include:

• Injection technique: Proper technique and site rotation to prevent lipodystrophy 2, 8
• Glucose monitoring: Self-monitoring techniques and interpretation 1, 2
• Hypoglycemia recognition and treatment: Symptoms and immediate management 1, 2
• Insulin storage: Avoid temperatures <36°F or >86°F 4
• Sick day management: Adjustments during illness 1, 2
• Needle safety: Never recap, bend, or break needles; never share pens or needles 4, 3

Critical Pitfalls to Avoid

1. Delaying insulin initiation: Do not delay in patients not achieving glycemic goals with oral medications 2

2. Relying on sliding scale alone: Scheduled insulin regimens are required, not correction insulin alone 1, 4

3. Overbasalization: Continuing to escalate basal insulin beyond 0.5-1.0 units/kg/day without adding prandial coverage 2

4. Abrupt discontinuation of oral medications: Risk of rebound hyperglycemia when starting insulin 8

5. Injecting into lipodystrophic areas: Results in erratic absorption and hyperglycemia 3

6. Using bedtime rapid-acting insulin: Risk of nocturnal hypoglycemia 4

7. Inadequate dose titration: Timely adjustments are essential for achieving glycemic goals 1, 2