Insulin Degludec (Tresiba) Dosing and Management
Starting Dose Recommendations
For adults with type 2 diabetes who are insulin-naïve, start insulin degludec at 10 units once daily. 1 This is the FDA-approved initial dose and represents a straightforward, evidence-based starting point that minimizes complexity while providing effective basal coverage.
For adults with type 1 diabetes who are insulin-naïve, the recommended starting dose is approximately one-third to one-half of the total daily insulin requirement, with the remainder given as short-acting insulin divided among meals. 1 As a general rule, calculate the initial total daily insulin dose as 0.2–0.4 units/kg body weight, then allocate one-third to one-half to degludec. 1
For metabolically stable patients with type 1 diabetes, a typical starting point is 0.5 units/kg/day total daily insulin, with approximately 40–50% given as basal insulin (degludec) and the remainder as prandial insulin. 2, 3 This translates to roughly 0.2–0.25 units/kg/day of degludec for most patients.
Titration Schedule
Increase the degludec dose by 2 units every 3–4 days if fasting glucose is 140–179 mg/dL, and by 4 units every 3–4 days if fasting glucose is ≥180 mg/dL. 1, 3 The target fasting plasma glucose is 80–130 mg/dL. 3
The FDA label explicitly states that the recommended interval between dose increases is 3 to 4 days, allowing sufficient time to assess the full glucose-lowering effect before making further adjustments. 1 This conservative approach is particularly important with degludec given its ultra-long duration of action exceeding 42 hours. 4
If unexplained hypoglycemia (glucose <70 mg/dL) occurs, immediately reduce the degludec dose by 10–20%. 5, 3
Unique Dosing Flexibility
Degludec can be administered once daily at any time of day in adults, with the timing allowed to vary from day to day. 1 This represents a major advantage over other basal insulins. However, in pediatric patients, degludec must be administered at the same time every day. 1
For adults who miss a dose, inject the missed dose during waking hours upon discovery, ensuring at least 8 hours have elapsed between consecutive injections. 1 For pediatric patients who miss a dose, contact the healthcare provider for guidance and monitor blood glucose more frequently. 1
Clinical trials have demonstrated that degludec maintains efficacy and low nocturnal hypoglycemia rates even when dosing intervals vary substantially from day to day. 6, 7 This flexibility addresses a major barrier to insulin adherence, particularly for patients with unpredictable schedules or those who travel frequently. 6
Switching from Other Insulins
Adults with Type 1 or Type 2 Diabetes
Start degludec at the same unit dose as the total daily long- or intermediate-acting insulin unit dose. 1 No dose conversion is needed when switching from glargine, detemir, or NPH in adults.
Pediatric Patients (≥1 Year)
Start degludec at 80% of the total daily long- or intermediate-acting insulin unit dose to minimize hypoglycemia risk. 1 This 20% reduction is critical in children, who have higher hypoglycemia risk during insulin transitions.
Safety Considerations and Hypoglycemia Risk
Degludec significantly reduces nocturnal hypoglycemia compared to insulin glargine while achieving equivalent HbA1c reduction. In type 1 diabetes, nocturnal confirmed hypoglycemia was 25% lower with degludec (p=0.021). 4 In type 2 diabetes, overall confirmed hypoglycemia was 18% lower (p=0.0359) and nocturnal hypoglycemia was 25% lower (p=0.0399) with degludec. 4
The mechanism underlying this benefit is degludec's ultra-long, flat, and stable action profile with duration exceeding 42 hours, which provides more consistent glucose-lowering without peaks. 4, 7 This pharmacokinetic profile translates to highly predictable glucose control from dose to dose. 6
Monitor blood glucose before each meal and at bedtime during titration. 3 Daily fasting glucose checks are essential to guide dose adjustments. 3
Dose Adjustments for Special Circumstances
Dose adjustments may be needed with changes in physical activity, meal patterns, renal or hepatic function, or during acute illness to minimize hypoglycemia or hyperglycemia risk. 1
For hospitalized patients on high-dose home insulin (≥0.6 units/kg/day), reduce the total daily dose by 20% upon admission to prevent hypoglycemia. 3
For elderly patients (>65 years) or those with renal impairment, start with lower doses of 0.1 units/kg/day to reduce hypoglycemia risk. 3
Critical Threshold: When to Add Prandial Insulin
When basal insulin approaches 0.5–1.0 units/kg/day without achieving glycemic targets, add prandial insulin rather than continuing to escalate basal insulin alone. 5 Clinical signals of "over-basalization" include basal dose >0.5 units/kg/day, bedtime-to-morning glucose differential ≥50 mg/dL, hypoglycemia episodes, and high glucose variability. 5
For type 2 diabetes patients requiring prandial coverage, start with 4 units of rapid-acting insulin before the largest meal or use 10% of the current basal dose. 5
Formulation and Administration
Degludec is available in two concentrations: U-100 (100 units/mL) and U-200 (200 units/mL). 1
- U-100 FlexTouch pen: Delivers doses in 1-unit increments, up to 80 units per injection 1
- U-200 FlexTouch pen: Delivers doses in 2-unit increments, up to 160 units per injection 1
- U-100 vial: 10 mL multiple-dose vial 1
Do NOT perform dose conversion when using degludec pens—the dose window shows the actual units to be delivered. 1 The U-200 formulation is particularly useful for patients requiring high basal insulin doses, as it reduces injection volume. 7
Never share degludec pens, needles, or syringes between patients, even if the needle is changed, due to risk of blood-borne pathogen transmission. 1
Contraindications
Degludec is contraindicated during episodes of hypoglycemia and in patients with hypersensitivity to insulin degludec or any excipients. 1
Common Pitfalls to Avoid
Do not use degludec as monotherapy in type 1 diabetes—it must be used concomitantly with short-acting insulin. 1 Failure to provide prandial coverage in type 1 diabetes can precipitate diabetic ketoacidosis. 5
Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis, as this can cause hyperglycemia; sudden change to an unaffected area may cause hypoglycemia. 1 Rotate injection sites systematically. 2
Do not delay dose adjustments when hypoglycemia occurs—studies show 75% of hospitalized patients with hypoglycemia receive no basal insulin adjustment before the next dose. 5
Do not continue escalating degludec beyond 0.5–1.0 units/kg/day without addressing postprandial hyperglycemia, as this leads to over-basalization with increased hypoglycemia risk and suboptimal control. 5
Expected Clinical Outcomes
In pediatric trials (ages 1–17 years), degludec achieved equivalent long-term glycemic control (HbA1c 7.9% vs 7.8%) compared to detemir, with significant fasting plasma glucose reduction (−1.29 mmol/L vs +1.10 mmol/L, p=0.0090) at 30% lower basal insulin dose (0.38 U/kg vs 0.55 U/kg). 8 Notably, hyperglycemia with ketosis was significantly reduced with degludec (0.7 vs 1.1 per patient-year, p=0.0066). 8
The majority (64%) of detemir-treated patients required twice-daily administration to achieve targets, whereas degludec maintained control with once-daily dosing. 8