What is the comparison between Tresiba (insulin degludec) and Lantus (insulin glargine) for diabetes management?

Comparison of Tresiba (Insulin Degludec) and Lantus (Insulin Glargine)

Tresiba (insulin degludec) offers superior hypoglycemia protection, particularly at night, compared to Lantus (insulin glargine U-100), while providing equivalent glycemic control—making it the preferred basal insulin for patients at risk for hypoglycemia or requiring flexible dosing schedules. 1, 2, 3, 4

Glycemic Control: Equivalent Efficacy

Both insulins achieve similar HbA1c reductions across multiple trials:

• In type 1 diabetes, degludec achieved identical HbA1c reduction to glargine U-100 at 52 weeks (treatment difference -0.01% [95% CI: -0.14 to 0.11]), with approximately 40% of patients in both groups reaching HbA1c <7%. 1, 2

• In type 2 diabetes, degludec demonstrated non-inferior glycemic control to glargine U-100 over 104 weeks, with an estimated treatment difference of only 0.07% (95% CI: -0.07 to 0.22). 3

• Time in range (TIR) was modestly but significantly better with degludec: 72.1% versus 70.7% for glargine U-100 (difference of 20.6 minutes/day in target range of 3.9-10.0 mmol/L). 4

The American Diabetes Association guidelines acknowledge that newer long-acting basal analogs like degludec may confer lower hypoglycemia risk compared to U-100 glargine in patients with type 1 diabetes. 5

Hypoglycemia: Tresiba's Key Advantage

The most clinically significant difference favors Tresiba for hypoglycemia reduction:

Nocturnal Hypoglycemia

• Type 1 diabetes: Degludec reduced nocturnal confirmed hypoglycemia by 25% compared to glargine U-100 (4.41 vs 5.86 episodes per patient-year; rate ratio 0.75 [0.59-0.96]). 2

• Type 2 diabetes: Degludec reduced nocturnal hypoglycemia by 40% over 104 weeks (0.27 vs 0.46 episodes per patient-year, p=0.002). 3

• Recent CGM data showed degludec reduced nocturnal time below range (<3.9 mmol/L) by 12.7 minutes per night compared to glargine U-100 (treatment difference -0.88% [95% CI: -1.34, -0.42]). 4

Severe Hypoglycemia

• In the DEVOTE cardiovascular outcomes trial with 7,637 high-risk type 2 diabetes patients, degludec reduced severe hypoglycemia by 40% compared to glargine U-100 (rate ratio 0.60 [0.48-0.76], p<0.001), with 4.9% versus 6.6% of patients experiencing events. 1

Pharmacokinetic Differences Explain Clinical Benefits

Tresiba has an ultra-long duration of action exceeding 42 hours, compared to Lantus's 24-hour profile:

• Glargine has an onset of approximately 1 hour with a relatively peakless profile lasting up to 24 hours. 6, 7

• Degludec's extended half-life allows for more flexible dosing timing (can vary injection time by 8-40 hours between doses without compromising control). 1

• The flatter, more stable pharmacokinetic profile of degludec explains its reduced nocturnal hypoglycemia risk. 8, 2

Dosing Flexibility: Tresiba's Practical Advantage

Degludec can be administered at varying times of day without loss of efficacy, whereas glargine requires consistent daily timing:

• Degludec was successfully studied with alternating morning/evening administration at intervals of 8-40 hours between doses. 1, 9

• The American Diabetes Association emphasizes that glargine should be administered at a consistent time each day to maintain stable blood glucose levels. 6

• This flexibility makes degludec superior for patients with irregular schedules, shift workers, or those with adherence challenges. 1

Cardiovascular Safety: Reassuring Long-Term Data

Initial concerns about cardiovascular risk with degludec were definitively resolved:

• The DEVOTE trial demonstrated non-inferior cardiovascular safety: degludec versus glargine U-100 hazard ratio for MACE was 0.91 (95% CI: 0.78-1.06). 1

• Early meta-analysis concerns about a 60% increase in cardiovascular events were not confirmed in this definitive 7,637-patient trial. 9, 1

Formulation Considerations

Tresiba is available in both U-100 and U-200 concentrations, while standard Lantus is U-100 (though U-300 glargine/Toujeo exists as a separate product):

• Degludec U-200 allows delivery of higher doses in smaller volumes (600 units per 3 mL pen versus 300 units for U-100). 1

• The U-200 formulation creates potential for dosing errors if confused with U-100 products—prescribers must specify concentration clearly. 1, 9

• U-300 glargine (Toujeo) requires approximately 10-18% higher daily doses compared to U-100 glargine due to modestly lower efficacy per unit. 6

Clinical Decision Algorithm

Choose Tresiba (degludec) for:

• Patients with recurrent nocturnal hypoglycemia on glargine 2, 3
• Those requiring flexible dosing schedules (shift workers, irregular routines) 1
• Patients with established cardiovascular disease requiring proven CV safety 1
• Those needing high insulin doses (U-200 formulation available) 1

Choose Lantus (glargine U-100) for:

• Cost-sensitive situations where hypoglycemia risk is low 9
• Patients already well-controlled on glargine without hypoglycemia issues 3
• Settings where U-100 concentration standardization reduces medication errors 9

Both are equivalent for:

• Achieving target HbA1c reductions 1, 3
• Overall confirmed hypoglycemia rates (though nocturnal rates favor degludec) 2
• Weight gain and injection site reactions 3

Important Caveats

• Neither insulin should be diluted or mixed with other insulins or solutions. 6

• Both require dose titration based on fasting glucose targets (typically 3.9-5.0 mmol/L for type 2 diabetes). 3, 4

• When basal insulin exceeds 0.5 units/kg/day with A1C still above target, consider adding GLP-1 receptor agonists or prandial insulin rather than continuing to escalate basal insulin alone. 5, 6

• The ADA/EASD consensus recommends GLP-1 receptor agonists as the preferred injectable medication before insulin for most patients with type 2 diabetes, though basal insulin remains appropriate when extreme hyperglycemia is present. 5