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endocrine:insulin:glargine

Insulin Glargine

Insulin glargine is a long-acting basal insulin analog used for background glucose control.

It provides a relatively flat, 24-hour insulin profile with minimal peak.

Insulin Therapy


Mechanism of Action

Glargine binds to the insulin receptor (tyrosine kinase receptor).

This activates:

  • IRS signaling pathways
  • PI3K/Akt cascade
  • GLUT4 translocation in muscle and adipose tissue

Primary basal function:

  • Suppresses hepatic gluconeogenesis
  • Provides steady background insulin

Structural Modification & Protraction

Glargine differs from human insulin by:

  • Replacement of asparagine at A21 with glycine
  • Addition of two arginine residues at B31 and B32

These modifications:

  • Shift isoelectric point
  • Make insulin soluble in acidic solution (in vial)
  • Cause precipitation in neutral subcutaneous tissue

After injection:

  • Microprecipitates form in subcutaneous tissue
  • Slow, continuous release of insulin monomers

This creates a prolonged, relatively peakless effect.


Pharmacokinetics

Onset:

  • ~1–2 hours

Peak:

  • Minimal or no pronounced peak

Duration:

  • ~24 hours (dose-dependent)

Compared to:

  • NPH → no pronounced peak, lower nocturnal hypoglycemia
  • Detemir → longer duration in most patients
  • Degludec → shorter duration

Typically given once daily.


Clinical Use

  • Basal insulin in Type 1 Diabetes
  • Basal insulin in Type 2 Diabetes

Often combined with:


Advantages

  • Once-daily dosing
  • Reduced nocturnal hypoglycemia compared to NPH
  • More stable glucose control
  • Predictable pharmacokinetics

Adverse Effects

  • Hypoglycemia
  • Weight gain
  • Injection site reactions

Hypoglycemia risk increases with:

  • Excess dosing
  • Reduced caloric intake
  • Increased activity

Glargine vs Other Basal Insulins

NPH:

  • Has peak
  • Higher hypoglycemia risk

Detemir:

  • Albumin-binding
  • May require twice-daily dosing

Degludec:

  • Ultra-long duration (>42 hours)
  • Most stable pharmacokinetic profile

Glargine:

  • 24-hour duration
  • Flat profile
  • Once-daily dosing
  • Widely used

Clinical Pearls

  • Long-acting basal insulin
  • Precipitates in subcutaneous tissue
  • Minimal peak
  • Once-daily dosing
  • Lower nocturnal hypoglycemia than NPH
  • Foundation of basal-bolus therapy

endocrine/insulin/glargine.txt · Last modified: by andrew2393cns