How should Awiqli (insulin icodec) be initiated and titrated in an adult with type 1 or type 2 diabetes requiring basal insulin?

Awiqli (Insulin Icodec) Initiation and Titration

For adults with type 2 diabetes requiring basal insulin, start Awiqli at 70 units once weekly (or 50 units weekly in patients with low BMI, chronic kidney disease, or Asian ethnicity), and titrate by ±20 units weekly based on three pre-breakfast glucose measurements targeting 80-130 mg/dL. 1, 2

Type 2 Diabetes Management

Insulin-Naïve Patients

Starting Dose:

• Standard: 70 units once weekly (equivalent to 10 units daily basal insulin) 1, 2
• Lower dose (50 units weekly) for patients with:
  • Low body mass index
  • Chronic kidney disease with reduced GFR
  • Hepatic impairment 1
• Asian patients: 30-70 units weekly per regional labels (China: 70 units; Japan: 30-70 units) 1

Key Pharmacology: Awiqli has a half-life of 196 hours (~8 days) due to strong albumin binding, reaching steady state in 3-4 weeks without loading dose 1

Switching from Daily Basal Insulin

Calculate weekly dose = (total daily basal insulin dose) × 7 1

Optional Loading Strategy for Faster Control:

• Week 1 only: Add 50% loading dose = (daily dose × 7) × 1.5, rounded to nearest 10 units
• Practical calculation: daily dose × 10.5 units 1
• Critical: Remove this loading dose from week 2 onward to prevent hypoglycemia 1
• Omit loading dose if: Patient frequently misses daily injections (may overestimate actual insulin need) 1

Clinical Evidence: Loading dose achieves steady state in 2-3 weeks versus 3-4 weeks without loading 1

Titration Protocol

Monitoring Requirements:

• Minimum 3 pre-breakfast glucose measurements weekly
• Start titration from week 2 (no loading) or week 3 (with loading) 1

Titration Algorithm (from ONWARDS trials):

• Adjust ±20 units weekly based on pre-breakfast glucose target 80-130 mg/dL (4.4-7.2 mmol/L) 1
• Measure glucose 2 days prior to and on day of next injection
• If any value below target: titrate based on lowest value
• If all values above target: titrate based on mean of three measurements 1

Conservative Titration (±10 units): Use smaller adjustments for high-risk patients: 1

• Age ≥65 years
• Preserved insulin sensitivity
• Hepatic or renal impairment
• History of hypoglycemia or hypoglycemia unawareness

Clinical Outcomes

Efficacy Data (ONWARDS 1-5 trials):

• Superior HbA1c reduction versus daily insulin glargine U-100: -0.18% difference (95% CI: -0.29% to -0.08%) 2
• Improved time-in-range: 4.27% greater (approximately 1 hour/day more) 2
• Hypoglycemia rates: Similar to daily basal insulins in type 2 diabetes 1
• 56.5% achieved HbA1c <7% versus 44.6% with glargine 2

Type 1 Diabetes Considerations

Awiqli is approved for type 1 diabetes but requires heightened caution 1

Critical Safety Concern: ONWARDS 6 trial showed increased risk of severe/clinically significant hypoglycemia in type 1 diabetes compared to insulin degludec, despite non-inferior glycemic control 3

Recommendation: Use with extreme caution in type 1 diabetes; daily basal insulins remain preferred unless specific patient factors favor weekly dosing 3

Administration Details

Injection Technique:

• Subcutaneous injection into thigh, upper arm, or abdomen 2
• Rotate injection sites to prevent lipodystrophy 2
• Available as 700 units/mL in prefilled FlexTouch pens (3 mL, 1.5 mL, 1 mL) 2
• Never transfer to syringe - risk of severe overdose 2

Dosing Flexibility:

• Can adjust by minimum 10-unit increments for fine-tuning once stable 1
• Steady-state insulin action distributed relatively evenly across the week (12-16% per day) 1

Common Pitfalls to Avoid

1. Forgetting to remove loading dose after week 1 → hypoglycemia risk 1
2. Transferring insulin to syringe → severe overdose 2
3. Aggressive titration in elderly/renal impairment → hypoglycemia 1
4. Inadequate glucose monitoring → need minimum 3 measurements weekly 1
5. Using in pregnancy or prolonged hospitalization → switch to daily insulin 1

Contraindications and Cautions

Absolute Contraindications:

• Active hypoglycemia
• Hypersensitivity to insulin icodec 2

Exercise Caution:

• History of severe hypoglycemia or hypoglycemia unawareness 1
• Recent cardiovascular events (excluded from trials) 1
• Severe renal impairment (use lower starting dose) 1

Switching Back to Daily Insulin

When needed (pregnancy, hospitalization):

• Calculate daily dose = (last weekly Awiqli dose) ÷ 7 1
• Begin titration 2 weeks after last Awiqli dose (or earlier if glucose >180 mg/dL) 1
• Monitor daily pre-breakfast glucose 1