What is Ryzodeg Insulin
Ryzodeg (insulin degludec/insulin aspart, also known as IDegAsp) is a fixed-ratio co-formulation combining 70% ultra-long-acting basal insulin degludec with 30% rapid-acting prandial insulin aspart in a single injection, designed to provide both basal and mealtime glucose coverage. 1, 2
Pharmacological Profile
- Insulin degludec provides ultra-long-acting basal coverage with a flat, stable glucose-lowering profile lasting >42 hours, with less day-to-day variability than insulin glargine 1
- Insulin aspart targets postprandial hyperglycemia with rapid onset of action 2
- This combination allows simultaneous coverage of both fasting and postprandial glucose with fewer daily injections compared to traditional basal-bolus regimens 3, 4
Clinical Advantages
- Reduces injection burden: Provides basal-plus coverage with one injection instead of multiple daily injections required for basal-bolus therapy 3, 4
- Lower hypoglycemia risk: Particularly nocturnal hypoglycemia compared to premixed insulins and some basal-bolus regimens 3, 1
- Flexible dosing: Can be administered once or twice daily depending on glycemic needs 4, 2
When to Initiate Ryzodeg
Ideal Clinical Scenarios
Ryzodeg should be considered as an insulin initiation option in type 2 diabetes patients with severe hyperglycemia (A1C >9-10%) and/or when postprandial hyperglycemia is a major concern, particularly when you want to avoid the complexity of basal-bolus therapy. 2
Specific Indications:
- Insulin-naive patients with type 2 diabetes inadequately controlled on maximal doses of oral antidiabetic drugs 3, 4, 1
- Patients requiring intensification beyond basal insulin alone when A1C remains above target despite optimized basal insulin (>0.5 units/kg/day) 5
- Alternative to premixed insulins in patients who need both basal and prandial coverage but want more flexibility than traditional premixed formulations 4
- Patients with type 1 diabetes as a simplified alternative to 4-5 injection basal-bolus regimens (once daily IDegAsp plus 2 doses of rapid-acting insulin) 4
How to Initiate Ryzodeg
Starting Dose
Begin with 10 units once daily administered with the largest or most carbohydrate-rich meal of the day. 2
Dose Calculation Alternatives:
- 0.1-0.2 units/kg/day based on body weight and degree of hyperglycemia 5
- For patients switching from basal insulin: use the same total daily basal insulin dose as the starting IDegAsp dose 2
Timing of Administration
- Administer with the main meal (largest or most carbohydrate-rich meal) 2
- Must be given with a meal due to the rapid-acting insulin aspart component 2
- Can be administered within 15 minutes before or after starting the meal 2
Dose Titration Protocol
Titrate weekly in 2-unit increments based on fasting plasma glucose (FPG) measurements from the preceding 3 days. 2
Titration Targets:
- Adjust dose to achieve individualized FPG targets (typically 80-130 mg/dL) 2
- Monitor both fasting and postprandial glucose to guide adjustments 2
- If hypoglycemia occurs, reduce dose by 2-4 units or 10-15% 6
Intensification from Once Daily to Twice Daily
When to Intensify
Consider advancing to twice-daily IDegAsp when A1C remains above target despite adequate FPG control on once-daily dosing, or when postprandial glucose excursions at other meals become problematic. 2
Specific Triggers:
- A1C >7% (or individualized target) despite optimized once-daily dosing 2
- Elevated postprandial glucose at meals other than the one covered by once-daily injection 2
- Pre-dinner or bedtime hyperglycemia despite acceptable FPG 2
How to Intensify to Twice Daily
- Split the total daily dose: Administer with the two largest meals of the day 2
- Starting approach: Divide current once-daily dose equally between breakfast and dinner, then titrate each dose independently 2
- Continue weekly titration in 2-unit steps for each injection based on pre-meal glucose values 2
Medication Adjustments When Starting Ryzodeg
Continue These Medications:
- Metformin: Always continue unless contraindicated 7
- SGLT2 inhibitors: Can continue but may need IDegAsp dose reduction 2
- GLP-1 receptor agonists: Can continue but may need IDegAsp dose reduction 2
Discontinue or Reduce These Medications:
- Sulfonylureas: Discontinue or significantly reduce dose to minimize hypoglycemia risk 7, 2
- DPP-4 inhibitors: Discontinue (contraindicated with GLP-1 component) 7
- Standalone GLP-1 agonists: Discontinue if previously prescribed 7
Clinical Outcomes and Real-World Evidence
In real-world studies, IDegAsp initiation resulted in A1C reductions of approximately 1.4% from baseline, with significant improvements in FPG (-46 mg/dL) and modest weight reduction (-1 kg). 8
- Superior long-term glycemic control compared to insulin glargine when used once daily in insulin-naive patients 4
- Numerically lower rates of overall and nocturnal hypoglycemia compared to basal insulin alone 4
- Fewer hypoglycemic episodes versus premixed insulins and basal-bolus therapy when used twice daily 4
- Well-tolerated with low rates of adverse events (4.3% in real-world studies) 8
Common Pitfalls and Caveats
Do not use IDegAsp in patients with previous severe GI intolerance to GLP-1 agonists, as the insulin aspart component may cause similar issues; consider prandial insulin addition to basal insulin instead. 7
Additional Warnings:
- Must be given with meals: Unlike pure basal insulin, cannot be given at bedtime without food due to rapid-acting component 2
- Not interchangeable with other premixed insulins: Different pharmacokinetic profile requires specific dosing approach 1
- Avoid overbasalization: If doses exceed 0.5 units/kg/day without adequate A1C control, consider alternative intensification strategies rather than continuing to increase IDegAsp 5, 6
- Patient education critical: Ensure patients understand the need for consistent meal timing and carbohydrate content 2