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.
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:
- Rapid-acting insulin (basal-bolus regimen)
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
- Albumin-binding
- May require twice-daily dosing
- 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
Related
endocrine/insulin/glargine.txt · Last modified: by andrew2393cns
