Insulin Degludec vs. Glargine for Basal Insulin Therapy
For most patients with type 1 or type 2 diabetes requiring basal insulin, insulin glargine (Lantus/Toujeo) should be the preferred initial choice over insulin degludec (Tresiba) based on cost-effectiveness, despite degludec's modest reduction in nocturnal hypoglycemia. 1
Cost-Effectiveness Analysis
Insulin degludec is probably of low value compared with insulin glargine when added to usual care in type 2 diabetes, with an estimated cost of $406,000 per quality-adjusted life-year (QALY) gained when used as basal insulin only, and $192,000 per QALY when used as basal-bolus therapy. 1
The cost difference is driven largely by hypoglycemic event models, but randomized controlled trials excluded persons at highest hypoglycemia risk, making severe hypoglycemia rare and event estimates unstable. 1
At current U.S. pricing, degludec costs approximately $407 per 1,000 units (median AWP) versus $340 per 1,000 units for glargine U-100, representing a 20% price premium. 1
Clinical Efficacy Comparison
Glycemic Control
Both degludec and glargine achieve equivalent HbA1c reduction when titrated to target fasting glucose levels, with degludec demonstrating noninferiority in allowing patients to reach an HbA1c target of 7%. 2, 3, 4
In the BEGIN Once Long trial of 1,030 insulin-naive type 2 diabetes patients, degludec reduced HbA1c by 1.06% versus 1.19% with glargine over 52 weeks, with an estimated treatment difference of 0.09% (95% CI -0.04 to 0.22), confirming noninferiority. 4
In silico head-to-head comparison of glargine U-300 versus degludec U-100 showed no statistically significant difference in percent time in glucose target range (70-140 mg/dL). 5
Hypoglycemia Risk
Degludec reduces nocturnal confirmed hypoglycemia by approximately 35% compared with glargine U-100 (0.25 vs. 0.39 episodes per patient-year of exposure; P = 0.038), but overall confirmed hypoglycemia rates are similar (1.52 vs. 1.85 episodes per patient-year). 4
The reduction in nocturnal hypoglycemia with degludec is statistically significant but clinically modest, translating to approximately 0.14 fewer nocturnal episodes per patient-year. 4
Long-acting basal analogs (U-100 glargine or detemir) reduce symptomatic and nocturnal hypoglycemia compared with NPH insulin, though these advantages are modest and may not persist over time. 1
Longer-acting basal analogs (U-300 glargine or degludec) may convey lower hypoglycemia risk compared with U-100 glargine when used in clinical practice. 1
Pharmacokinetic Advantages of Degludec
Degludec provides uniform "peakless" action extending over more than 24 hours with high consistency from dose to dose, forming soluble multihexamers that are slowly and continuously absorbed after subcutaneous injection. 2, 3
This ultra-long and stable action profile allows for more flexible dosing schedules, maintaining effectiveness and low nocturnal hypoglycemia rates even when dosing intervals vary substantially from day to day. 2
Degludec exhibits less intra-patient variability in glucose-lowering activity compared with glargine. 6
Clinical Scenarios Favoring Degludec
High Hypoglycemia Risk Populations
Consider degludec over glargine in patients with recurrent nocturnal hypoglycemia despite optimized glargine dosing, as degludec's ultra-long duration and reduced variability may provide superior overnight coverage. 2, 3
Patients with hypoglycemia unawareness or those at high risk for severe hypoglycemia may benefit from degludec's lower nocturnal hypoglycemia rate. 2
Dosing Flexibility Requirements
Degludec is the preferred option for patients requiring flexible dosing schedules (shift workers, irregular meal patterns) because it maintains efficacy and safety even when dosing intervals vary substantially day to day. 2
The ultra-long half-life of degludec allows for administration at any time of day without loss of efficacy, unlike glargine which requires consistent timing. 2
Clinical Scenarios Favoring Glargine
Cost-Sensitive Situations
Glargine should be the first-line basal insulin for most patients when cost is a consideration, as it provides equivalent glycemic control at 20% lower cost than degludec. 1
Glargine follow-on (biosimilar) products cost approximately $190 per 1,000 units (median AWP), representing a 44% discount compared with reference glargine and 53% discount compared with degludec. 1
Standard Basal Insulin Initiation
For insulin-naive patients with type 2 diabetes, start glargine at 10 units once daily (or 0.1-0.2 units/kg/day) and titrate by 2-4 units every 3 days until fasting glucose reaches 80-130 mg/dL. 1, 7
This standard titration approach is well-established for glargine and provides excellent glycemic control in most patients without the added cost of degludec. 1, 7
Renal Function Considerations
Both degludec and glargine require dose reduction in patients with chronic kidney disease, with type 2 diabetes patients at CKD stage 5 requiring a 50% reduction in total daily insulin dose. 7
Patients with renal impairment have increased risk of hypoglycemia with all insulins due to decreased insulin clearance, requiring closer monitoring regardless of which basal insulin is chosen. 7
The modest reduction in nocturnal hypoglycemia with degludec may be more clinically meaningful in patients with advanced CKD who have higher baseline hypoglycemia risk. 4
Practical Dosing and Administration
Conversion Between Insulins
When switching from glargine to degludec, use a unit-for-unit conversion initially, then titrate based on fasting glucose monitoring over the subsequent 2-4 weeks. 8
For patients in very tight glycemic control or at high hypoglycemia risk, consider reducing the initial degludec dose by 10-20% when converting from glargine. 8
Titration Protocols
Both insulins should be titrated using the same algorithm: increase by 2 units every 3 days if fasting glucose is 140-179 mg/dL, or by 4 units every 3 days if fasting glucose is ≥180 mg/dL, targeting 80-130 mg/dL. 1, 7
If hypoglycemia occurs without clear cause, reduce the dose by 10-20% immediately. 7
Critical Threshold for Basal Insulin
- When basal insulin (either degludec or glargine) exceeds 0.5 units/kg/day and approaches 1.0 units/kg/day without achieving glycemic targets, add prandial insulin rather than continuing to escalate basal insulin alone to avoid overbasalization. 1, 7
Common Pitfalls to Avoid
Do not assume degludec's higher cost is justified by hypoglycemia reduction alone—the absolute difference in nocturnal hypoglycemia is small (0.14 episodes per patient-year) and may not warrant the substantial cost premium for most patients. 1, 4
Do not delay insulin initiation in patients not achieving glycemic goals with oral medications, as this prolongs hyperglycemia exposure and increases complication risk. 7
Do not discontinue metformin when starting either basal insulin unless contraindicated, as the combination provides superior glycemic control with reduced insulin requirements and less weight gain. 7, 4
Do not continue escalating basal insulin beyond 0.5-1.0 units/kg/day without addressing postprandial hyperglycemia, as this leads to overbasalization with increased hypoglycemia risk and suboptimal control. 1, 7
Algorithm for Insulin Selection
Step 1: Assess Cost Constraints
- If cost is a primary concern → Choose glargine (or glargine biosimilar) 1
- If cost is not a barrier → Proceed to Step 2
Step 2: Evaluate Hypoglycemia Risk
- If recurrent nocturnal hypoglycemia on optimized glargine → Switch to degludec 2, 4
- If hypoglycemia unawareness or high severe hypoglycemia risk → Consider degludec 2
- If standard hypoglycemia risk → Choose glargine 1
Step 3: Assess Lifestyle Factors
- If irregular schedule requiring flexible dosing times → Choose degludec 2
- If consistent daily routine → Choose glargine 1
Step 4: Consider Renal Function