Insulin is the most effective glucose-lowering therapy available.

It replaces or supplements endogenous insulin when pancreatic beta-cell function is inadequate or absent.

Used in:

• Type 1 Diabetes (required)
• Advanced Type 2 Diabetes
• DKA / HHS
• Severe hyperglycemia
• Hospital settings

→ Diabetes Pharmacology

Insulin binds to the insulin receptor (a tyrosine kinase receptor).

This activates:

• IRS signaling pathways
• PI3K/Akt cascade
• GLUT4 translocation (muscle & adipose)

Effects:

Liver:

• ↓ Gluconeogenesis
• ↑ Glycogen synthesis
• ↑ Lipogenesis

Muscle:

• ↑ Glucose uptake
• ↑ Glycogen storage

Adipose:

• ↑ Glucose uptake
• ↓ Lipolysis

Insulin is anabolic.

Insulins are categorized by onset and duration.

• Lispro
• Aspart
• Glulisine

Onset: 10–30 minutes Duration: 3–5 hours

Used for:

• Mealtime glucose control
• Correction dosing

• Regular Insulin

Onset: 30–60 minutes Duration: 6–8 hours

Used in:

• IV infusion (DKA)
• Some prandial regimens

• NPH

Duration: ~12–18 hours

Older basal insulin option.

• Glargine
• Detemir

Provide steady background insulin.

• Degludec

Very flat, prolonged profile (>24 hours).

Physiologic insulin secretion includes:

• Basal insulin (background suppression of hepatic glucose production)
• Bolus insulin (mealtime glucose control)

Modern therapy mimics this:

Basal insulin:

• Once daily (glargine, degludec)

Bolus insulin:

• Rapid-acting insulin before meals

This is the most physiologic regimen.

Step 1:

• Start basal insulin
• Titrate based on fasting glucose

Step 2:

• Add prandial insulin if needed

Continue:

• Metformin when possible
• Consider combination with:
  • GLP-1 Receptor Agonists
  • SGLT2 Inhibitors

Common:

• Hypoglycemia
• Weight gain

Serious:

• Severe hypoglycemia
• Hypokalemia (high-dose therapy)

Hypoglycemia symptoms:

• Sweating
• Tremor
• Confusion
• Seizures (severe)

Insulin deficiency leads to:

• Unchecked lipolysis
• Ketone production
• Metabolic acidosis (DKA)

Treatment requires:

• IV Regular Insulin
• Fluid resuscitation
• Electrolyte management

Compared to:

• Sulfonylureas → direct replacement vs stimulation
• Metformin → more potent glucose lowering
• GLP-1 Receptor Agonists → more hypoglycemia, more weight gain
• SGLT2 Inhibitors → no intrinsic CV benefit

Insulin is unmatched in glucose-lowering potency.

• Most potent antihyperglycemic therapy
• Required in Type 1 Diabetes
• Basal suppresses hepatic glucose output
• Bolus controls meals
• Causes weight gain
• Hypoglycemia is primary risk
• Continue metformin when possible

• Diabetes Pharmacology
• Metformin
• GLP-1 Receptor Agonists
• SGLT2 Inhibitors
• Sulfonylureas