How do I switch a patient from insulin degludec injection to the fixed‑ratio co‑formulation insulin degludec/insulin aspart (Ryzodeg) injection?

Switching from Insulin Degludec to Insulin Degludec/Insulin Aspart (Ryzodeg)

Start Ryzodeg at the same total daily dose as your current degludec, administered once or twice daily with your largest meal(s), then titrate weekly based on fasting glucose targets.

---

Initial Conversion Strategy

When switching from basal insulin degludec (Tresiba) to the fixed-ratio co-formulation Ryzodeg (insulin degludec/insulin aspart 70/30), begin with a unit-for-unit conversion of your current degludec dose. 1, 2

• If currently on degludec 30 units once daily: Start Ryzodeg 30 units once daily with your largest meal 1, 2
• Timing is critical: Administer Ryzodeg immediately before (0–15 minutes) your most carbohydrate-rich meal of the day 1, 3
• The 70% degludec component provides the same basal coverage you had previously, while the 30% aspart component now addresses postprandial glucose excursions at that meal 4, 5

---

Dosing Frequency Decision

Once-Daily (OD) Ryzodeg

• Appropriate when: Your current basal insulin provides adequate fasting control but you need coverage for one major meal 1, 2
• Starting dose: Equal to your current degludec dose, given with your largest or most carbohydrate-heavy meal 1, 3
• Example: If on degludec 40 units at bedtime → switch to Ryzodeg 40 units before dinner 1

Twice-Daily (BID) Ryzodeg

• Appropriate when: You have significant postprandial hyperglycemia at two meals, or your HbA1c remains >7% despite optimized basal insulin 1, 3
• Starting dose: Divide your current degludec dose approximately 2:1 (larger dose with breakfast, smaller with dinner) 1, 2
• Example: If on degludec 60 units → start Ryzodeg 40 units before breakfast and 20 units before dinner 1

---

Titration Protocol

Adjust Ryzodeg weekly (not every 3 days like pure basal insulin) in 2-unit increments based on fasting plasma glucose. 1, 2

Weekly Titration Algorithm

Fasting Glucose	Dose Adjustment
>126 mg/dL (7.0 mmol/L)	Increase by 2 units
72–126 mg/dL (4.0–7.0 mmol/L)	No change
<72 mg/dL (4.0 mmol/L)	Decrease by 2 units

1, 2

• Target fasting glucose: 80–130 mg/dL (individualized based on hypoglycemia risk) 1
• If hypoglycemia occurs: Reduce the implicated dose by 10–20% immediately 6

---

Intensification from Once-Daily to Twice-Daily

Consider advancing from OD to BID Ryzodeg when:

1. HbA1c remains >7% after 3–6 months despite achieving fasting glucose targets 1, 3
2. Postprandial glucose consistently exceeds 180 mg/dL at a second meal 1
3. Patient preference for fewer total daily injections compared to basal-bolus therapy 3

Conversion Method

• Calculate total daily Ryzodeg dose (e.g., 50 units OD)
• Split approximately 60% before breakfast, 40% before dinner (e.g., 30 units breakfast, 20 units dinner) 1, 2
• Titrate each dose independently based on pre-meal glucose at the subsequent meal 1

---

Special Populations and Situations

Patients with Severe Hyperglycemia (HbA1c >10%)

• Ryzodeg may be preferable to degludec alone as initial insulin therapy because it addresses both fasting and postprandial hyperglycemia from the start 1, 3
• Starting dose: 10 units with the largest meal, titrated weekly 1, 2

Switching from Basal-Bolus Regimens

• If currently on degludec + multiple rapid-acting injections: Ryzodeg BID can reduce injection burden while maintaining glycemic control 1, 3
• Calculate total daily insulin dose (basal + all prandial doses)
• Start Ryzodeg at 70–80% of this total, split between breakfast and dinner 1

Hospitalized Patients

• Ryzodeg can be initiated or continued in non-critically ill hospitalized patients 1
• Dose may need reduction (10–20%) if oral intake is poor 6, 1
• Monitor glucose before each meal and at bedtime 6

---

Combination Therapy Adjustments

Sulfonylureas

• Discontinue or reduce dose by 50% when starting Ryzodeg to prevent hypoglycemia 1, 3

GLP-1 Receptor Agonists

• Can be continued with Ryzodeg; may allow for lower insulin doses 1
• Reduce Ryzodeg by 10–20% when adding a GLP-1 RA to prevent hypoglycemia 1

SGLT2 Inhibitors

• Can be continued; may require Ryzodeg dose reduction of 10–20% 1

Metformin

• Continue at maximum tolerated dose (up to 2000–2550 mg/day) for insulin-sparing effects 6, 7

---

Monitoring Requirements

During the first 4 weeks after switching:

• Check fasting glucose daily to guide weekly dose adjustments 1, 2
• Check 2-hour postprandial glucose after the meal(s) where Ryzodeg is administered 1
• Monitor for hypoglycemia especially in the first 2 weeks 1, 3
• Reassess HbA1c at 3 months to determine if further intensification is needed 7, 1

---

Critical Pitfalls to Avoid

• Do not titrate Ryzodeg every 3 days like pure basal insulin; the aspart component requires weekly adjustments to assess full effect 1, 2
• Do not administer Ryzodeg at bedtime as the aspart component increases nocturnal hypoglycemia risk 6, 1
• Do not use Ryzodeg as a correction dose between meals; it is a scheduled insulin only 6
• Do not assume 1:1 conversion from premixed insulins; Ryzodeg has different pharmacokinetics requiring individualized dosing 1, 2
• Do not delay intensification to BID if postprandial glucose remains >180 mg/dL at multiple meals despite adequate fasting control 1, 3

---

Expected Clinical Outcomes

• Similar or improved HbA1c reduction compared to basal insulin alone, with additional postprandial glucose control 4, 5
• Lower risk of nocturnal hypoglycemia compared to premixed human insulins or NPH-based regimens 4, 5, 3
• Fewer daily injections compared to basal-bolus therapy (1–2 vs. 4–5 injections) 1, 3
• Greater flexibility in meal timing compared to traditional premixed insulins due to the ultra-long degludec component 4, 5