Diabetes Pharmacology

Diabetes Mellitus results from failure of insulin to exert its normal metabolic effects.

Type 1 Diabetes:

Type 2 Diabetes:

Pharmacology only makes sense when viewed through mechanism.


The Mechanism of Diabetes

Dr. O conceptualizes Type 2 Diabetes as:

This process disrupts the “8-Organ Model”:

Diabetes is not simply hyperglycemia — it is metabolic signaling failure.


Nutrient Handling → Pathology

Carbohydrates

Glucose delivered too rapidly:

Problem is not glucose alone — It is glucose delivered too fast, too often.


Fats

Low-quality fats:


Proteins (BCAAs)

Branched-chain amino acids:

Worst metabolic combination:

Maximal insulin resistance + maximal insulin demand.


Insulin Physiology

Pancreatic beta cell:

Incretins amplify this:

Broken down by:

Insulin action:

Liver:

Muscle & Adipose:

Chronic overactivation → receptor downregulation → insulin resistance.


Hyperglycemia Damage

Acute damage:

Chronic damage:

End-organ damage:


Renal Glucose Handling

In the proximal tubule:

When glucose exceeds transport maximum:

SGLT2 Inhibitors


Pharmacology of Diabetes

1. Hypoglycemics (Increase Insulin Effect)

These agents increase insulin levels and carry hypoglycemia risk. Insulin Therapy

Rapid-Acting (Prandial)

Short-Acting

Intermediate-Acting

Long-Acting (Basal)

Ultra-Long Acting

Sulfonylureas

Meglitinides

2. Anti-Hyperglycemics (Low Hypoglycemia Risk)

These agents improve glycemia without directly increasing insulin secretion.

Biguanides

Thiazolidinediones (TZDs)

GLP-1 Receptor Agonists

Dual GLP-1/GIP Incretin Agonists

Triple Incretin Agonists

SGLT2 Inhibitors


Modern Cardiometabolic Integration

Diabetes management now prioritizes:

High-impact classes:

Cardiovascular Pharmacology


Learning Framework

By completing this module, you should be able to: