Choosing Between Insulin Glargine and Insulin Degludec in Adults with Diabetes

Direct Recommendation

For most adults with type 1 or type 2 diabetes requiring basal insulin, start with insulin glargine U-100 as the first-line basal insulin due to its lower cost, established safety profile, and equivalent glycemic efficacy compared to degludec. 1 Reserve insulin degludec for patients with recurrent nocturnal hypoglycemia despite optimized glargine dosing, those requiring flexible injection timing, or when hypoglycemia risk substantially limits insulin titration. 2, 3

Glycemic Efficacy: Equivalent A1C Reduction

Both insulin glargine and insulin degludec achieve comparable A1C reductions when titrated to target fasting glucose (80–130 mg/dL), with no clinically meaningful difference in overall glycemic control. 2, 3
Degludec produces a modestly greater reduction in fasting plasma glucose (approximately –0.37 mmol/L or –6.7 mg/dL) compared to glargine, though this difference rarely translates to meaningful A1C improvement. 2
U-300 glargine has a longer duration of action than U-100 glargine but modestly lower efficacy per unit administered, requiring slightly higher total daily doses to achieve equivalent fasting glucose control. 1

Hypoglycemia Risk: Degludec's Primary Advantage

Nocturnal Hypoglycemia

Degludec reduces nocturnal confirmed hypoglycemia by approximately 25% in type 1 diabetes compared to glargine U-100 in randomized trials. 4, 2
In type 2 diabetes, degludec significantly lowers the rate of overall and nocturnal hypoglycemia compared to glargine or detemir, though the absolute risk reduction is smaller than in type 1 diabetes. 2, 3
The risk of severe hypoglycemia is not significantly different between degludec and glargine in head-to-head trials. 2

Clinical Context for Hypoglycemia Benefit

Prioritize degludec in patients with recurrent nocturnal hypoglycemia (≥2 episodes per month with glucose <70 mg/dL between midnight and 6 AM) despite optimized glargine timing and dosing. 2, 3
Consider degludec in elderly patients (>65 years) with hypoglycemia unawareness, where even modest reductions in nocturnal hypoglycemia carry substantial clinical benefit. 1
In patients without frequent hypoglycemia, the incremental benefit of degludec does not justify its substantially higher cost. 4

Dosing Flexibility: Degludec's Unique Feature

Degludec's ultra-long duration of action (>42 hours) permits flexible once-daily dosing at varying times of day without loss of efficacy or increased hypoglycemia risk. 4, 5, 3
Glargine U-100 and U-300 must be administered at the same time each day to maintain stable 24-hour basal coverage. 4, 3
Reserve degludec for patients with unpredictable schedules (e.g., shift workers, caregivers with irregular routines) where consistent daily timing is impractical. 5, 3
For adults, if a degludec dose is missed, inject during waking hours upon discovery, ensuring at least 8 hours between consecutive injections. 6
For pediatric patients on degludec, contact the healthcare provider for guidance if a dose is missed and monitor glucose more frequently until the next scheduled dose. 6

Age-Specific Considerations

Elderly Patients (>65 Years)

Start with lower doses (0.1–0.25 U/kg/day) of either glargine or degludec to minimize hypoglycemia risk in older adults with increased insulin sensitivity. 1
Degludec may be preferred in elderly patients with cognitive impairment or inconsistent meal timing, as its flexible dosing reduces the risk of missed or mistimed injections. 5, 3
Exercise caution with both agents in geriatric patients, as hypoglycemia may be difficult to recognize and initial dosing should be conservative. 7

Pediatric Patients (≥1 Year)

Both glargine and degludec are approved for pediatric use in type 1 and type 2 diabetes. 6, 7
When switching pediatric patients to degludec from another basal insulin, start at 80% of the total daily long- or intermediate-acting insulin dose to minimize hypoglycemia risk. 6
Glargine has more extensive pediatric safety data, with established use in children as young as 6 years in controlled trials. 7
Pediatric patients with type 1 diabetes on glargine have a higher incidence of severe symptomatic hypoglycemia compared to adults, warranting close monitoring. 7

Renal and Hepatic Impairment

Renal Impairment

Both glargine and degludec require dose reduction and increased glucose monitoring in patients with renal impairment, as insulin clearance decreases with declining kidney function. 7
For CKD stage 5, reduce total daily insulin by 50% in type 2 diabetes and by 35–40% in type 1 diabetes, regardless of whether glargine or degludec is used. 1
Titrate conservatively in patients with eGFR <45 mL/min/1.73 m² to avoid hypoglycemia, as both agents have prolonged action in renal impairment. 1
No specific pharmacokinetic studies have been conducted for glargine in renal impairment, but clinical experience supports dose reduction and frequent monitoring. 7

Hepatic Impairment

Frequent glucose monitoring and dose adjustment are necessary for both glargine and degludec in hepatic impairment, though specific pharmacokinetic data are lacking. 7
No clear advantage exists for either agent in hepatic dysfunction; choose based on hypoglycemia risk and cost considerations. 7

Dosing Convenience and Formulations

Glargine Formulations

Glargine U-100 is available in vials and prefilled pens, offering flexibility for patients who prefer vials or require precise dose adjustments. 1
Glargine U-300 (Toujeo) is available only in prefilled pens and delivers three times the concentration per volume, reducing injection volume for patients requiring high basal doses (>40 units). 1
U-300 glargine has a longer duration of action than U-100 glargine but requires slightly higher total daily doses due to modestly lower per-unit efficacy. 1

Degludec Formulations

Degludec U-100 is available in vials and prefilled FlexTouch pens, with the pen delivering doses in 1-unit increments up to 80 units per injection. 6
Degludec U-200 is available only in prefilled FlexTouch pens, delivering doses in 2-unit increments up to 160 units per injection, ideal for patients requiring high basal doses. 6
No dose conversion is needed when using degludec U-100 or U-200 pens, as the dose window displays the number of insulin units to be delivered. 6
Degludec U-200 and glargine U-300 are available only in prefilled pens to minimize dosing errors associated with concentrated insulins. 1, 6

Cost Considerations

Acquisition Costs

Glargine U-100 (generic/biosimilar) costs approximately $95–$136 per 1,000 units (NADAC/AWP), making it the most affordable basal insulin option. 1
Degludec U-100 costs approximately $114–$142 per 1,000 units (NADAC/AWP), representing a modest premium over generic glargine. 1
Degludec U-200 costs approximately $85–$113 per 1,000 units (NADAC/AWP), offering cost savings for patients requiring high basal doses (>60 units/day). 1
Glargine U-300 costs approximately $290–$363 per 1,000 units (NADAC/AWP), making it the most expensive basal insulin formulation. 1

Cost-Effectiveness

Cost-effectiveness analyses estimate that degludec costs approximately $406,000 per quality-adjusted life-year (QALY) gained compared to glargine, reflecting limited value for most patients. 4
The higher cost of degludec is justified only in patients with recurrent nocturnal hypoglycemia, where reduced hypoglycemia-related healthcare utilization may offset acquisition costs. 4, 3
For patients without frequent hypoglycemia, generic glargine U-100 offers the best value, with equivalent glycemic efficacy at substantially lower cost. 1, 4

Practical Dosing Algorithms

Initiating Basal Insulin in Type 2 Diabetes

Start glargine U-100 or degludec at 10 units once daily (or 0.1–0.2 U/kg/day) for insulin-naïve patients. 1, 6
Administer glargine at the same time each day (typically bedtime); degludec can be given at any consistent or varying time. 4, 6, 3
Titrate by 2 units every 3 days if fasting glucose is 140–179 mg/dL; increase by 4 units every 3 days if fasting glucose ≥180 mg/dL. 1
Target fasting glucose 80–130 mg/dL. 1
When basal insulin approaches 0.5 U/kg/day without achieving A1C goals, add prandial insulin or a GLP-1 receptor agonist rather than further basal escalation. 1

Switching from Glargine to Degludec

Adults with type 1 or type 2 diabetes: Start degludec at the same unit dose as the total daily glargine dose. 6
Pediatric patients (≥1 year): Start degludec at 80% of the total daily glargine dose to minimize hypoglycemia risk. 6
Monitor fasting glucose daily for the first week after switching and adjust doses by 2–4 units every 3–4 days as needed. 6

Switching from Degludec to Glargine

Start glargine at the same unit dose as the total daily degludec dose for most patients. 6
Administer glargine at a consistent time each day (unlike degludec's flexible timing). 4, 3
Monitor for increased nocturnal hypoglycemia risk during the first 2 weeks after switching, as glargine has a shorter duration of action. 2, 3

Common Pitfalls and How to Avoid Them

Pitfall 1: Choosing Degludec for All Patients Based on Hypoglycemia Data

Degludec's hypoglycemia benefit is most pronounced in patients with recurrent nocturnal hypoglycemia; in patients without frequent hypoglycemia, the incremental benefit does not justify the higher cost. 4, 2
Start with generic glargine U-100 for most patients and reserve degludec for those with documented hypoglycemia issues. 1, 4

Pitfall 2: Failing to Adjust Doses When Switching Between Agents

When switching pediatric patients to degludec, reduce the dose to 80% of the prior basal insulin to avoid hypoglycemia. 6
When switching from glargine U-100 to U-300, expect to increase the total daily dose by 10–20% due to U-300's modestly lower per-unit efficacy. 1

Pitfall 3: Administering Glargine at Varying Times

Glargine U-100 and U-300 must be given at the same time each day to maintain stable 24-hour coverage; inconsistent timing increases hypoglycemia and hyperglycemia risk. 4, 3
If consistent timing is impractical, switch to degludec, which permits flexible dosing without loss of efficacy. 5, 3

Pitfall 4: Using Concentrated Insulins Without Proper Education

Degludec U-200 and glargine U-300 are available only in prefilled pens to minimize dosing errors; never attempt to draw these insulins into standard syringes. 1, 6
If a vial of concentrated insulin is prescribed, ensure the patient uses the appropriate high-concentration syringe (e.g., U-500 syringe for U-500 regular insulin). 1

Pitfall 5: Overlooking Renal Impairment

Both glargine and degludec require dose reduction in renal impairment, as insulin clearance decreases with declining kidney function. 7
For CKD stage 5, reduce total daily insulin by 50% in type 2 diabetes and by 35–40% in type 1 diabetes, regardless of the basal insulin used. 1

Summary Algorithm for Choosing Between Glargine and Degludec

Start with generic glargine U-100 for most patients due to lower cost and equivalent glycemic efficacy. 1, 4
Switch to degludec if:
- Recurrent nocturnal hypoglycemia (≥2 episodes/month) despite optimized glargine dosing. 2, 3
- Unpredictable daily schedule requiring flexible injection timing. 5, 3
- Elderly patient with hypoglycemia unawareness or cognitive impairment. 5, 3
Consider glargine U-300 or degludec U-200 for patients requiring high basal doses (>60 units/day) to reduce injection volume. 1, 6
In pediatric patients, start degludec at 80% of the prior basal insulin dose when switching from another basal insulin. 6
In renal impairment (CKD stage 5), reduce total daily insulin by 50% (type 2 diabetes) or 35–40% (type 1 diabetes), regardless of the basal insulin chosen. 1

In an adult with type 1 or type 2 diabetes, how should I choose between insulin glargine (U‑100/U‑300) and insulin degludec (U‑100/U‑200) considering age, hypoglycemia risk, renal or hepatic impairment, dosing convenience, and cost?

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