How to Calculate the Dose of Ryzodeg (Insulin Degludec/Insulin Aspart)
Start Ryzodeg at 10 units once daily with the largest or most carbohydrate-rich meal, then titrate by 2 units once weekly based on fasting plasma glucose targets. 1
Initial Dosing Strategy
For insulin-naive patients with type 2 diabetes, the recommended starting dose is 10 units administered with the most carbohydrate-rich meal of the day 1. This approach is particularly appropriate when:
- Severe hyperglycemia is present (A1C ≥9% or blood glucose ≥300-350 mg/dL) 2
- Postprandial hyperglycemia is a major concern 1
- You want to provide both basal and prandial coverage from the outset 1
Alternative weight-based calculation: You can also use 0.1-0.2 units/kg/day as the starting dose, which aligns with standard basal insulin initiation guidelines 2. For a 70 kg patient, this would be 7-14 units once daily.
Dose Titration Algorithm
Titrate the dose weekly in 2-unit increments based on fasting plasma glucose readings 1. The target fasting glucose is 80-130 mg/dL 2.
Specific titration steps:
- If fasting glucose is 140-179 mg/dL: increase by 2 units 2
- If fasting glucose is ≥180 mg/dL: increase by 4 units 2
- If hypoglycemia occurs without clear cause: reduce dose by 10-20% immediately 2
The weekly titration schedule (rather than every 3 days) is specific to Ryzodeg and differs from standard basal insulin protocols, reflecting the ultra-long duration of action of the degludec component 1, 3.
Intensification from Once-Daily to Twice-Daily Dosing
When to intensify: Consider advancing from once-daily to twice-daily Ryzodeg when 1:
- A1C remains above target despite optimal once-daily dosing
- Significant postprandial glucose excursions occur at meals other than the one covered by the single injection
- Total daily dose approaches 0.5 units/kg/day without achieving glycemic goals 2
How to split the dose: When moving to twice-daily dosing, administer Ryzodeg with the two largest meals of the day, distributing the total daily dose based on the carbohydrate content of each meal 1.
Critical Threshold: Recognizing Overbasalization
Stop escalating Ryzodeg when the total dose exceeds 0.5 units/kg/day and consider adding separate rapid-acting insulin at other meals rather than continuing to increase Ryzodeg 2. Clinical signals of overbasalization include 2:
- Basal dose >0.5 units/kg/day
- Bedtime-to-morning glucose differential ≥50 mg/dL
- Hypoglycemia episodes
- High glucose variability
Special Considerations for Ryzodeg
Timing flexibility: Unlike traditional premixed insulins, Ryzodeg can be administered with the main meal of the day, and the timing can be adjusted based on patient meal patterns 1. The insulin aspart component provides prandial coverage for that meal, while the degludec component provides basal coverage over 24+ hours 4, 3.
Switching from other insulin regimens 1:
- From basal insulin alone: Start with the same total daily dose as the previous basal insulin
- From premixed insulin once-daily: Use the same total daily dose
- From premixed insulin twice-daily: Calculate total daily dose and reduce by 20%, then give as once-daily Ryzodeg initially
Concomitant Medications
Continue metformin unless contraindicated when initiating Ryzodeg 2.
Adjust or discontinue sulfonylureas as they frequently need dose reduction or discontinuation to prevent hypoglycemia 1.
When adding GLP-1 receptor agonists or SGLT2 inhibitors, the Ryzodeg dose may need to be decreased by 10-20% to prevent hypoglycemia 1.
Common Pitfalls to Avoid
- Do not delay intensification when once-daily dosing is insufficient—advance to twice-daily or add separate prandial insulin rather than continuing to escalate a single daily dose beyond 0.5 units/kg/day 2, 1
- Do not titrate too aggressively—weekly adjustments are appropriate for Ryzodeg due to its ultra-long half-life of approximately 25 hours 3, 5
- Do not ignore the need for prandial coverage at other meals—Ryzodeg provides prandial coverage only for the meal with which it is administered 1