How do I switch a patient from Lantus (insulin glargine) to Ryzodeg (insulin degludec/insulin aspart)?

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

For patients transitioning from Lantus to Ryzodeg, start Ryzodeg at the same total daily basal insulin dose as the current Lantus dose, administered once daily, recognizing that Ryzodeg contains both basal (degludec 70%) and rapid-acting (aspart 30%) components that will require adjustment of any existing prandial insulin. 1, 2

Understanding the Key Differences

Ryzodeg is fundamentally different from Lantus because it combines ultra-long-acting insulin degludec (70%) with rapid-acting insulin aspart (30%) in a single injection, whereas Lantus provides only basal coverage. 2 This means you are not simply switching one basal insulin for another—you are adding prandial coverage with the aspart component. 2

• Insulin degludec has a duration of action exceeding 42 hours with a flat, stable glucose-lowering profile and less day-to-day variability than glargine. 2
• The aspart component in Ryzodeg provides mealtime coverage, though its effect is somewhat blunted compared to separate aspart administration. 3
• Degludec reaches maximum concentration at 10-12 hours with a half-life of 17-21 hours, roughly double that of glargine. 3

Initial Conversion Dosing

Start Ryzodeg at a dose equal to the patient's current total daily Lantus dose, administered once daily with the largest meal (typically dinner). 1, 2, 4 For example, if the patient takes 40 units of Lantus daily, begin with 40 units of Ryzodeg once daily with dinner. 1, 4

• The 70% degludec component will provide basal coverage similar to the previous Lantus dose. 2
• The 30% aspart component will provide prandial coverage for that meal. 2
• If the patient is currently taking separate rapid-acting insulin with meals, reduce or eliminate the rapid-acting dose at the meal where Ryzodeg is administered, since the aspart component provides coverage. 2

Adjusting Existing Prandial Insulin

Because Ryzodeg contains 30% insulin aspart, you must reduce any existing mealtime rapid-acting insulin at the meal where Ryzodeg is given to avoid hypoglycemia. 2

• If the patient takes 10 units of rapid-acting insulin with dinner and you administer 40 units of Ryzodeg with dinner, the Ryzodeg provides approximately 12 units of aspart (30% of 40 units). 2
• Eliminate the separate rapid-acting insulin dose at the Ryzodeg meal initially, then titrate based on post-prandial glucose monitoring. 2
• Continue separate rapid-acting insulin at other meals as previously prescribed. 2

Titration Protocol After Conversion

Titrate Ryzodeg by 2-4 units once or twice weekly based on fasting plasma glucose, targeting 80-130 mg/dL. 1, 4

• Increase by 2 units every 3 days if fasting glucose is 140-179 mg/dL. 1
• Increase by 4 units every 3 days if fasting glucose is ≥180 mg/dL. 1
• If hypoglycemia occurs (glucose <70 mg/dL), reduce the dose by 10-20% immediately. 1
• Monitor 2-hour post-prandial glucose after the meal with Ryzodeg to assess adequacy of the aspart component, targeting <180 mg/dL. 1

Monitoring Requirements

Check fasting glucose daily during the first 3-4 weeks after switching to guide dose adjustments. 1, 4

• Measure 2-hour post-prandial glucose after the meal where Ryzodeg is administered. 1
• Check pre-meal glucose before other meals to guide any remaining separate rapid-acting insulin doses. 1
• Reassess the regimen every 3 days during active titration. 1
• Measure HbA1c after 3 months to evaluate overall glycemic control. 1

Special Considerations for Flexible Dosing

Degludec's ultra-long duration of action (>42 hours) allows for flexible injection timing if needed, though consistency is preferred. 2

• If a dose is missed, adults should inject during waking hours upon discovery, ensuring at least 8 hours between consecutive injections. 5
• Pediatric patients who miss a dose should contact their healthcare provider for guidance. 5
• The flat pharmacokinetic profile of degludec reduces the risk of hypoglycemia with timing variations compared to glargine. 2

Critical Threshold: When to Stop Basal Escalation

When Ryzodeg dose approaches 0.5-1.0 units/kg/day without achieving glycemic targets, add separate rapid-acting insulin at other meals rather than continuing to escalate Ryzodeg alone. 1, 4

• Clinical signals of "overbasalization" include basal dose >0.5 units/kg/day, bedtime-to-morning glucose differential ≥50 mg/dL, hypoglycemia episodes, and high glucose variability. 1
• At this threshold, the patient needs more prandial coverage at meals other than where Ryzodeg is administered. 1

Advantages of Ryzodeg Over Separate Basal-Bolus

Ryzodeg reduces the number of daily injections by combining basal and prandial insulin in one injection, which may improve adherence. 2

• In clinical trials, Ryzodeg was noninferior to insulin detemir in type 1 diabetes with the potential to reduce injection burden. 2
• The coformulation provides predictable pharmacodynamics despite the blunted aspart effect. 3, 2
• Ryzodeg is particularly appropriate for initiating insulin therapy in type 2 diabetes patients inadequately controlled on oral agents. 2

Common Pitfalls to Avoid

Do not simply substitute Ryzodeg unit-for-unit for Lantus without accounting for the aspart component—this will cause hypoglycemia at the meal where Ryzodeg is given if separate rapid-acting insulin is continued at full dose. 2

• Never administer Ryzodeg at bedtime as the sole injection, because the aspart component will cause nocturnal hypoglycemia. 1, 2 Ryzodeg should be given with the largest meal. 2
• Do not transfer Ryzodeg from the FlexTouch pen into a syringe for administration. 5
• Avoid mixing Ryzodeg with other insulins in the same syringe. 5
• Do not delay dose adjustments when hypoglycemia occurs—reduce by 10-20% immediately. 1

Hypoglycemia Management

Treat any glucose <70 mg/dL immediately with 15 grams of fast-acting carbohydrate, recheck in 15 minutes, and repeat if needed. 1

• If hypoglycemia occurs without an obvious cause, reduce the Ryzodeg dose by 10-20% before the next injection. 1
• Nocturnal hypoglycemia risk is lower with degludec-based regimens compared to glargine due to the flatter pharmacokinetic profile. 2

Expected Clinical Outcomes

Ryzodeg achieves similar glycemic control to separate basal-bolus regimens with potentially fewer injections and lower nocturnal hypoglycemia risk. 2

• Clinical trials demonstrate noninferior HbA1c reduction compared to insulin detemir in type 1 diabetes. 2
• The ultra-long duration and flat profile of degludec result in less within-patient day-to-day variability in glucose-lowering effect than glargine. 2
• Patients may experience improved treatment satisfaction due to reduced injection burden. 6