What generation of insulin is Levemir (detemir)?

Insulin Detemir is a Long-Acting Insulin Analogue

Insulin detemir (Levemir) is a long-acting insulin analogue that belongs to the second generation of basal insulins. 1 It represents an advancement over first-generation basal insulins like NPH (Neutral Protamine Hagedorn) insulin, offering more predictable glucose-lowering effects with less variability.

Characteristics of Insulin Detemir

• Mechanism of action: Detemir is a soluble long-acting human insulin analogue acylated with a 14-carbon fatty acid 2
• Binding properties: 98-99% albumin-bound in plasma, which contributes to its prolonged action 2, 3
• Duration of action: 5-23 hours depending on dose, with most doses providing effective coverage for up to 24 hours 2
• Pharmacokinetics: Slower, more prolonged absorption over 24 hours compared to NPH insulin 2

Advantages Over First-Generation Insulins

Detemir offers several clinical advantages compared to older basal insulins like NPH:

• Reduced hypoglycemia risk: Moderate-quality evidence shows fewer severe hypoglycemic events with detemir (OR, 0.37 [CI, 0.16 to 0.92]) compared to NPH insulin 1
• Less weight gain: High-quality evidence shows lower body weight with detemir than with NPH insulin (mean difference, −1.26 kg [CI, −1.78 to −0.73 kg]) 1
• More predictable effect: Less within-patient variability in glucose-lowering effect compared to both NPH insulin and insulin glargine 4

Clinical Applications

Detemir is indicated for basal insulin therapy in both type 1 and type 2 diabetes:

• Can be administered once or twice daily as part of basal-bolus insulin therapy 5
• Often administered at bedtime but can be given twice daily (morning and either before dinner or at bedtime) 6
• Particularly beneficial for patients experiencing frequent severe hypoglycemia with human insulin 1

Considerations for Use

Despite its advantages, the World Health Organization guidelines suggest:

• Human insulin (including NPH) remains the first-line insulin choice in resource-limited settings due to cost considerations 1
• Long-acting insulin analogues like detemir should be considered primarily for patients who experience frequent severe hypoglycemia with human insulin 1

Positioning Among Insulin Types

Insulin detemir represents an evolution in basal insulin therapy:

1. First generation: Human insulins (NPH)
2. Second generation: Long-acting analogues (detemir, glargine U100)
3. Newer generation: Ultra-long-acting analogues (degludec, glargine U300)

The American Diabetes Association and European Association for the Study of Diabetes recognize that long-acting insulin analogues like detemir have a modestly lower absolute risk for hypoglycemia compared with NPH insulin, though at a higher cost 1.

When selecting a basal insulin, clinicians should consider the patient's risk of hypoglycemia, cost considerations, and individual response to therapy.