Insulin Detemir

Approved Indications:

• Type 1 Diabetes Mellitus: For adults and children ≥2 years to provide basal insulin coverage as part of a basal-bolus regimen.
• Type 2 Diabetes Mellitus: For adults requiring basal insulin supplementation when oral antidiabetic therapy is insufficient.
• Diabetic Ketoacidosis (Adjunctive Use): Can be used as part of long-term basal therapy after stabilization.

Clinically Accepted Off-Label Uses:

• Gestational Diabetes Mellitus (GDM): Considered in selected cases when diet and lifestyle modifications are insufficient.
• Insulin Pump Therapy: Sometimes used in continuous subcutaneous infusion for basal coverage in specialized settings.

• Route: Subcutaneous injection.
• Timing: Once or twice daily, ideally at the same time each day to maintain consistent basal levels.
• Adult Dosing: Typically 0.1–0.2 units/kg once daily or 0.2 units/kg twice daily; adjust based on blood glucose monitoring.
• Pediatric Dosing: Individualized according to age, weight, and glycemic response; often started at 0.2 units/kg/day.
• Elderly / Renal / Hepatic Impairment: Dose adjustments may be necessary due to altered metabolism or insulin sensitivity; monitor closely.
• Combination Therapy: Can be used with short-acting insulin analogs for prandial control or with oral antidiabetic agents in type 2 diabetes.
• Special Instructions: Rotate injection sites to reduce risk of lipodystrophy. Do not mix with other insulin formulations in the same syringe.

Insulin Detemir is a long-acting insulin analog that binds to insulin receptors on hepatocytes, adipocytes, and muscle cells. Its fatty acid acylation allows reversible binding to albumin, resulting in slow and sustained absorption from subcutaneous tissue. Once bound to receptors, it activates tyrosine kinase signaling pathways, enhancing glucose uptake via GLUT4 transporters, promoting glycogen synthesis, and suppressing hepatic gluconeogenesis. This mechanism provides a steady basal insulin level, reducing fasting plasma glucose and overall glycemic variability.

• Absorption: Slow and predictable due to albumin binding; onset of action ~1–2 hours.
• Peak: Minimal pronounced peak; provides relatively flat basal insulin coverage.
• Duration: Up to 24 hours after a single daily dose; may require twice-daily administration in some patients.
• Distribution: High protein binding (~98–99%) to albumin in plasma.
• Metabolism: Degraded by proteolytic enzymes, primarily in liver and kidneys.
• Half-Life: Approximately 5–7 hours (varies with dose and patient characteristics).
• Elimination: Metabolites excreted mainly in urine; minimal active insulin remains.

• Pregnancy: Considered Category B; can be used when strict glycemic control is required. Maintains maternal and fetal glucose homeostasis.
• Lactation: Minimal transfer into breast milk; generally considered safe for breastfeeding mothers.
• Caution: Blood glucose should be monitored frequently in pregnancy; dose adjustments may be necessary postpartum.

• Primary Class: Antidiabetic agent.
• Subclass: Long-acting insulin analog (basal insulin).

• Known hypersensitivity to insulin detemir or any excipients.
• During episodes of hypoglycemia.
• Use in unmonitored intravenous settings (insulin detemir is not approved for IV use).

• Hypoglycemia: Most common and potentially severe adverse effect; careful monitoring required.
• Hypokalemia: Can occur during high-dose therapy; monitor potassium levels.
• Injection-Site Reactions: Rare but may include erythema, swelling, or lipohypertrophy.
• Switching Insulins: Requires careful titration to avoid hyper- or hypoglycemia.
• High-Risk Populations: Elderly, renal or hepatic impairment, and patients with irregular meal patterns are at increased risk of hypoglycemia.

Common:

• Hypoglycemia (fasting or postprandial).
• Injection site reactions (pain, redness, lipohypertrophy).

Less Common:

• Weight gain.
• Edema.

Rare but Serious:

• Severe allergic reactions, including anaphylaxis.
• Immune-mediated insulin resistance.

Timing:

• Hypoglycemia may occur anytime but is more likely during peak glucose-lowering effect or missed meals.

• Hypoglycemia Risk Increased By: Oral antidiabetics, beta-blockers, alcohol, salicylates.
• Hyperglycemia Risk Increased By: Corticosteroids, sympathomimetics, diuretics, thyroid hormones.
• Beta-blockers: May mask hypoglycemia symptoms.
• Enzyme Systems: Insulin detemir is not metabolized via CYP450; interactions are primarily pharmacodynamic.

• ADA recommends long-acting analogs like insulin detemir for basal coverage due to lower risk of nocturnal hypoglycemia compared to NPH insulin.
• Twice-daily dosing may be used in patients requiring more stable basal insulin coverage.
• Integration with continuous glucose monitoring improves individualized titration and glycemic control.

• Unopened Vials/Pens: Refrigerate at 2°C–8°C; do not freeze.
• In-Use Pens: May be stored at room temperature (<30°C) for up to 42 days.
• Protection: Avoid direct sunlight and excessive heat.
• Handling: Do not shake; roll gently to mix if needed.
• Disposal: Dispose of used needles and pens according to local sharps regulations.