====== 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.

→ [[endocrine:insulin:start|Insulin Therapy]]

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===== 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

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===== 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.

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===== Pharmacokinetics =====

Onset:
  * ~1–2 hours

Peak:
  * Minimal or no pronounced peak

Duration:
  * ~24 hours (dose-dependent)

Compared to:

  * [[endocrine:insulin:nph|NPH]] → no pronounced peak, lower nocturnal hypoglycemia
  * [[endocrine:insulin:detemir|Detemir]] → longer duration in most patients
  * [[endocrine:insulin:degludec|Degludec]] → shorter duration

Typically given once daily.

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===== Clinical Use =====

  * Basal insulin in Type 1 Diabetes
  * Basal insulin in Type 2 Diabetes

Often combined with:

  * Rapid-acting insulin (basal-bolus regimen)
  * [[endocrine:biguanides:metformin|Metformin]]
  * [[endocrine:glp1:start|GLP-1 Receptor Agonists]]
  * [[endocrine:sglt2:start|SGLT2 Inhibitors]]

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===== Advantages =====

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

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===== Adverse Effects =====

  * Hypoglycemia
  * Weight gain
  * Injection site reactions

Hypoglycemia risk increases with:

  * Excess dosing
  * Reduced caloric intake
  * Increased activity

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===== Glargine vs Other Basal Insulins =====

[[endocrine:insulin:nph|NPH]]:
  * Has peak
  * Higher hypoglycemia risk

[[endocrine:insulin:detemir|Detemir]]:
  * Albumin-binding
  * May require twice-daily dosing

[[endocrine:insulin:degludec|Degludec]]:
  * Ultra-long duration (>42 hours)
  * Most stable pharmacokinetic profile

Glargine:
  * 24-hour duration
  * Flat profile
  * Once-daily dosing
  * Widely used

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===== 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

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===== Related =====

  * [[endocrine:insulin:start|Insulin Therapy]]
  * [[endocrine:insulin:detemir|Detemir]]
  * [[endocrine:insulin:degludec|Degludec]]
  * [[endocrine:insulin:nph|NPH]]
  * [[endocrine:diabetes:start|Diabetes Pharmacology]]