For a patient with type 1 or type 2 diabetes needing basal insulin, should I start Tresiba (insulin degludec) or insulin glargine, considering dosing flexibility, nocturnal hypoglycemia risk, and cost?

Tresiba vs. Insulin Glargine: Clinical Decision Framework

Direct Recommendation

For most patients with type 1 or type 2 diabetes requiring basal insulin, start with insulin glargine (Lantus U-100 or biosimilars) as first-line therapy due to proven efficacy, lower cost, and extensive clinical experience. Reserve Tresiba (insulin degludec) for patients experiencing recurrent nocturnal hypoglycemia on glargine or those requiring exceptional dosing flexibility. 1

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Key Clinical Differences

Pharmacokinetic Profiles

• Tresiba (degludec) forms soluble multihexamers after subcutaneous injection that slowly convert to monomers, creating an ultra-long duration of action exceeding 42 hours with a flat, peakless profile and significantly lower day-to-day variability than glargine. 2, 3

• Insulin glargine uses an acidic pH formulation (pH ≈4) that precipitates in subcutaneous tissue, providing approximately 24-hour coverage with a relatively peakless profile, though with greater within-patient variability than degludec. 1, 4

Hypoglycemia Risk

• Nocturnal hypoglycemia occurs significantly less frequently with Tresiba compared to glargine in both type 1 and type 2 diabetes across multiple phase 3 trials, with clinically significant hypoglycemia (<54 mg/dL) rates of 0% vs. 6.0% (p=0.023) in head-to-head comparisons. 4, 5, 6

• Overall hypoglycemia rates are lower with degludec versus glargine or detemir in meta-analyses, though severe hypoglycemia rates remain similar between agents. 6

Dosing Flexibility

• Tresiba allows flexible dosing intervals (varying 8–40 hours between doses) without compromising glycemic control or increasing hypoglycemia risk, whereas glargine requires consistent daily timing. 2, 3, 5

• Both agents can be administered once daily, though glargine may require twice-daily dosing in some type 1 diabetes patients when once-daily administration fails to provide 24-hour coverage. 4

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Cost-Effectiveness Analysis

Insulin glargine is substantially more cost-effective than degludec. The American College of Physicians reports degludec costs $406,000 per QALY gained when used as basal-only therapy and $192,000 per QALY in basal-bolus regimens—both far exceeding standard willingness-to-pay thresholds of $50,000–$150,000 per QALY. 7, 1

Choose glargine when cost is a primary concern and hypoglycemia risk is acceptable. 1

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Patient Selection Algorithm

Start with Insulin Glargine (U-100) if:

• Cost is a significant barrier to adherence 1
• Patient achieves target glycemic control (HbA1c <7%) without problematic hypoglycemia on current glargine therapy 1
• Patient can maintain consistent daily injection timing 4
• No history of recurrent nocturnal hypoglycemia 4

Switch to Tresiba (Degludec) if:

• Recurrent nocturnal hypoglycemia (≥2 episodes per week with glucose <54 mg/dL) despite optimized glargine dosing 4, 1
• Significant glucose variability (bedtime-to-morning differential ≥50 mg/dL) on glargine 4
• Occupational or lifestyle requirements necessitate flexible dosing intervals (shift workers, irregular schedules) 2, 3
• Patient requires high-volume basal insulin (>80 units daily); degludec U-200 reduces injection volume 2, 3

Consider U-300 Glargine (Toujeo) Before Degludec if:

• Patient experiences nocturnal hypoglycemia on Lantus U-100 but cost remains a concern 4
• Toujeo provides longer duration than Lantus with lower hypoglycemia rates (<54 mg/dL) at lower cost than degludec 4

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Practical Dosing Considerations

Initial Dosing (Insulin-Naïve Patients)

• Type 2 diabetes: Start either agent at 10 units once daily or 0.1–0.2 units/kg/day 4, 8
• Type 1 diabetes: Start at 0.4–0.5 units/kg/day total insulin, with approximately 40–50% as basal insulin 4, 8

Conversion Between Agents

• Unit-for-unit conversion is generally appropriate when switching between glargine and degludec 1
• Reduce initial dose by 10–20% in patients at high hypoglycemia risk (elderly, renal impairment, hypoglycemia unawareness) 1
• When switching from Lantus U-100 to Toujeo U-300, increase daily dose by 10–18% (e.g., 66 U Lantus → 73–78 U Toujeo) due to non-bioequivalence 4

Titration Protocol (Identical for Both Agents)

• Fasting glucose 140–179 mg/dL: Increase by 2 units every 3 days 4, 8
• Fasting glucose ≥180 mg/dL: Increase by 4 units every 3 days 4, 8
• Target fasting glucose: 80–130 mg/dL 4, 8
• If hypoglycemia (<70 mg/dL) occurs: Reduce dose by 10–20% immediately 4, 8

Critical Threshold for Adding Prandial Insulin

When basal insulin exceeds 0.5 units/kg/day without achieving HbA1c targets, add prandial insulin or GLP-1 receptor agonist rather than continuing basal escalation with either degludec or glargine. 4, 1 Signs of "overbasalization" include:

• Basal dose >0.5 units/kg/day 4
• Bedtime-to-morning glucose differential ≥50 mg/dL 4
• Hypoglycemia despite overall hyperglycemia 4
• High glucose variability 4

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Formulation-Specific Considerations

Degludec Formulations

• U-100 (100 units/mL): Standard concentration for most patients 1, 2
• U-200 (200 units/mL): Reduces injection volume for patients requiring >80 units daily; available only in FlexTouch prefilled pens 2, 3
• Degludec/aspart coformulation (Ryzodeg): Combines basal and rapid-acting insulin in one injection; may reduce daily injection burden in type 1 diabetes 1, 2

Glargine Formulations

• U-100 (Lantus, Basaglar, Semglee): Standard concentration; biosimilars (Basaglar, Semglee) provide comparable efficacy at lower cost 4
• U-300 (Toujeo): Longer duration than U-100 with lower nocturnal hypoglycemia rates; requires 10–18% higher daily dose 4
• Glargine cannot be mixed or diluted with any other insulin due to acidic pH 4, 1

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Safety and Monitoring

Cardiovascular Concerns

• FDA meta-analysis suggested ~60% increase in cardiovascular events (composite of MI, stroke, CV death) with degludec, though this remains uncertain and requires longer-term data. 9 This concern has not been definitively resolved in subsequent trials.

Pregnancy

• Avoid degludec in pregnancy due to very limited clinical experience; glargine has more extensive safety data. 9

Hypoglycemia Management (Identical for Both Agents)

• Treat glucose <70 mg/dL with 15 g fast-acting carbohydrate, recheck in 15 minutes, repeat if needed 4, 8
• Never administer rapid-acting insulin at bedtime as sole correction dose with either basal insulin 4, 8

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Common Pitfalls to Avoid

• Do not delay insulin initiation in patients failing oral agents; prolonged hyperglycemia increases complication risk 4, 8
• Do not discontinue metformin when starting basal insulin unless contraindicated; metformin reduces insulin requirements by 20–30% 4, 8
• Do not continue escalating basal insulin beyond 0.5–1.0 units/kg/day without adding prandial coverage; this causes overbasalization with increased hypoglycemia 4, 1
• Do not switch to degludec solely for convenience without documented hypoglycemia or flexibility needs; cost-effectiveness is poor 7, 1

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Bottom Line

Start with insulin glargine U-100 (or biosimilars) for cost-effectiveness and proven safety. Switch to Tresiba only for patients with recurrent nocturnal hypoglycemia or exceptional dosing flexibility requirements. If nocturnal hypoglycemia occurs on Lantus U-100, try Toujeo U-300 before degludec to balance efficacy and cost. Both agents require identical titration protocols and achieve similar HbA1c reductions; the primary differentiators are hypoglycemia risk, dosing flexibility, and cost. 4, 1, 2, 6