What is the comparison between Degludec (Insulin Degludec) and Lantus (Insulin Glargine) for basal insulin therapy in patients with type 1 or 2 diabetes?

Insulin Degludec vs Lantus (Insulin Glargine) Comparison

Insulin degludec provides equivalent glycemic control to insulin glargine (Lantus) with significantly lower rates of nocturnal hypoglycemia, making it the preferred choice when hypoglycemia risk is a concern, though both are acceptable basal insulin options for type 1 and type 2 diabetes. 1

Glycemic Control: Equivalent Efficacy

Both insulin degludec and insulin glargine achieve similar reductions in HbA1c across multiple clinical trials:

• Non-inferiority confirmed: In head-to-head trials, degludec achieved HbA1c reductions equivalent to glargine U-100, with treatment differences of -0.01% (95% CI: -0.14% to 0.11%) in type 1 diabetes 2
• Fasting glucose advantage: Degludec produces significantly greater reductions in fasting plasma glucose compared to glargine, with mean differences of -0.37 mmol/L (95% CI: -0.473 to -0.267 mmol/L; P ≤ 0.001) 3
• Time in range superiority: In type 2 diabetes, degludec provides 1.43% more time in range (3.9-10.0 mmol/L) compared to glargine U-100, translating to approximately 21 additional minutes per day in target range 4

Hypoglycemia: Degludec's Primary Advantage

The most clinically significant difference favoring degludec is reduced nocturnal hypoglycemia:

• Nocturnal hypoglycemia reduction: Degludec reduces nocturnal hypoglycemia rates by 17-36% compared to glargine across diabetes types, with rate ratios of 0.83 in type 1 diabetes basal-bolus regimens, 0.64 in insulin-naïve type 2 diabetes, and 0.75 in type 2 diabetes basal-bolus regimens (all P < 0.05) 5
• Nocturnal time below range: Degludec reduces nocturnal time below 3.9 mmol/L by 0.88% compared to glargine U-100 (approximately 12.7 minutes per night), with significantly fewer nocturnal episodes <3.0 mmol/L 4
• Overall hypoglycemia: Meta-analyses confirm significantly lower rates of overall confirmed hypoglycemia with degludec versus glargine or detemir in both type 1 and type 2 diabetes 3
• Severe hypoglycemia: No significant difference in severe hypoglycemia rates between degludec and glargine in type 1 diabetes, though degludec showed 86% reduction in insulin-naïve type 2 diabetes (rate ratio 0.14, P < 0.05) 5

Pharmacological Properties Driving Clinical Differences

Degludec's ultra-long action profile explains its hypoglycemia advantage:

• Duration of action: Degludec provides >42 hours of glucose-lowering effect with a flat, stable profile versus glargine's approximately 24-hour duration 6
• Day-to-day variability: Degludec demonstrates significantly less within-patient variability in glucose-lowering effect compared to glargine, contributing to more predictable glycemic control 6, 7
• Absorption mechanism: Degludec forms soluble multihexamers that convert to monomers after subcutaneous injection, providing slow, continuous absorption without concentration peaks 7

Insulin Dosing Considerations

Degludec typically requires lower total daily insulin doses:

• Dose efficiency: In type 1 diabetes basal-bolus regimens and insulin-naïve type 2 diabetes, degludec requires significantly lower total daily insulin doses compared to glargine while achieving equivalent HbA1c control 5
• Starting doses: Both insulins can be initiated at 10 units daily or 0.1-0.2 units/kg/day in type 2 diabetes, with weekly titration of 10-15% or 2-4 units until fasting glucose targets are met 1

Guideline Recommendations and Clinical Context

Current American Diabetes Association guidelines position both insulins similarly:

• Type 1 diabetes: Both U-300 glargine and degludec may confer lower hypoglycemia risk compared to U-100 glargine, making them preferred options when hypoglycemia is problematic 1
• Type 2 diabetes: Longer-acting basal analogs (U-300 glargine or degludec) may convey lower hypoglycemia risk compared to U-100 glargine when used with oral agents 1
• Standard of care: Long-acting basal analogs (including both glargine and degludec) are associated with less hypoglycemia and weight gain compared to NPH insulin in type 1 diabetes 1

Flexible Dosing Advantage

Degludec uniquely permits flexible dosing schedules:

• Timing flexibility: Clinical trials demonstrate degludec can be administered at varying times each day (alternating 8-40 hour intervals) without compromising glycemic control, achieving non-inferiority to glargine with treatment difference of 0.17% (95% CI: 0.04% to 0.30%) 2, 6
• Clinical utility: This flexibility may benefit patients with irregular schedules, though consistent timing remains the standard recommendation for both insulins 8

Cost and Access Considerations

Cost remains a critical factor in insulin selection:

• Price increases: Insulin costs have risen steadily over two decades, making cost considerations important when selecting between analogs 1
• NPH alternative: Despite advantages of long-acting analogs, NPH insulin remains a more affordable option for some patients, though with higher hypoglycemia risk 1
• Concentrated formulations: Both U-300 glargine and U-200 degludec are available for patients requiring large insulin volumes 1, 8

Clinical Decision Algorithm

Choose insulin degludec over glargine when:

• Patient experiences recurrent nocturnal hypoglycemia on glargine 4, 3
• Patient has high hypoglycemia risk factors (elderly, renal impairment, hypoglycemia unawareness) 4
• Patient requires dosing flexibility due to irregular schedule 2, 6
• Fasting glucose remains elevated despite adequate glargine dosing 3, 5

Choose insulin glargine when:

• Cost is a primary barrier to treatment adherence 1
• Patient is well-controlled on glargine without hypoglycemia issues 1
• Institutional formulary restrictions limit degludec access 1

Important Caveats

Both insulins require proper administration technique:

• Glargine should not be diluted or mixed with other insulins due to its low pH 8
• Both should be administered at consistent times daily for optimal efficacy, though degludec permits more flexibility 8, 2
• Comprehensive patient education on injection technique, glucose monitoring, and hypoglycemia management remains essential regardless of insulin choice 1

When advancing therapy beyond basal insulin:

• If basal insulin dose exceeds 0.5 units/kg/day with HbA1c remaining above target, consider adding GLP-1 receptor agonists or prandial insulin rather than simply increasing basal insulin dose 8
• This applies equally to both degludec and glargine regimens 1