Can insulin degludec (insulin degludec) be taken twice per day?

Insulin Degludec Can Be Administered Twice Daily in Special Circumstances

Insulin degludec can be administered twice daily in specific clinical situations, though it is primarily designed and approved as a once-daily basal insulin due to its ultra-long duration of action exceeding 24 hours.

Standard Dosing of Insulin Degludec

• Insulin degludec is designed as an ultra-long-acting basal insulin with a half-life exceeding 25 hours 1
• It provides uniform ("peakless") action that extends over more than 24 hours with high consistency from dose to dose 2
• The standard administration is once-daily dosing, which produces a steady-state profile characterized by a near-constant effect 1

Evidence for Flexible Dosing

The primary advantage of insulin degludec over other basal insulins is its flexibility in dosing schedule:

• Clinical trials have demonstrated that insulin degludec tolerates day-to-day variation in dose timing while maintaining full efficacy and low risk of nocturnal hypoglycemia 3
• A 26-week randomized trial showed that varying the daily injection time of insulin degludec, creating intervals of 8-40 hours between injections, did not compromise glycemic control or safety compared to fixed dosing 4
• Another study in Japanese patients confirmed that flexible dosing (allowing ±8 hours from an agreed dosing time) was non-inferior to fixed dosing with respect to HbA1c reduction 5

Situations Where Twice-Daily Dosing May Be Considered

While once-daily dosing is standard, twice-daily administration may be appropriate in certain scenarios:

• For patients requiring very high doses of basal insulin (>0.5 units/kg/day), where combination therapy with GLP-1 receptor agonists is also recommended 6
• When transitioning from other twice-daily basal insulins like NPH or detemir (which sometimes requires twice-daily dosing)
• For patients who experience glycemic variability despite optimal once-daily dosing

Practical Considerations for Twice-Daily Dosing

If twice-daily dosing is implemented:

• Split the total daily dose between two injections, typically administering 50% in the morning and 50% in the evening
• Maintain consistent timing of injections when possible
• Monitor blood glucose closely during the transition period, as insulin requirements may change 6
• Be aware that insulin degludec is available in both U-100 and U-200 formulations, with U-200 being available only in prefilled pens to minimize dosing errors 6

Advantages of Insulin Degludec

• Reduced risk of nocturnal hypoglycemia compared to insulin glargine 2
• Ability to vary dosing time without compromising glycemic control 4, 5
• Higher day-to-day reproducibility and less within-day variability 6
• Particularly well-suited for patients with unpredictable schedules or those who travel frequently 3

Important Caveats

• Insulin degludec should not be mixed with other insulins due to its acidic pH 6
• When transitioning from other basal insulins to degludec, dose adjustments may be necessary, and blood glucose should be monitored closely 6
• Consider cost implications, as newer formulations like insulin degludec may be more expensive than standard formulations 6

While insulin degludec is primarily designed for once-daily administration, its ultra-long duration of action and flexible dosing profile make twice-daily administration feasible in specific clinical situations where improved glycemic control is needed.