Tirzepatide

Tirzepatide is a dual incretin agonist that activates both:

• GLP-1 receptors
• GIP receptors

It is the first FDA-approved dual GLP-1/GIP receptor agonist.

Brand names:

• Mounjaro (Type 2 Diabetes)
• Zepbound (Obesity)

→ Dual GLP-1/GIP Incretin Agonists

Tirzepatide combines two incretin pathways:

GLP-1 receptor activation:

• Increases glucose-dependent insulin secretion
• Decreases glucagon
• Slows gastric emptying
• Promotes satiety

GIP receptor activation:

• Enhances insulin secretion
• Modulates adipocyte metabolism
• May amplify anabolic and metabolic signaling

Net effects:

• Significant HbA1c reduction
• Profound weight loss
• Improved insulin sensitivity
• Reduced appetite

Hypoglycemia risk is low unless combined with insulin or sulfonylureas.

• Glycemic control
• Greater A1c reduction than many GLP-1 receptor agonists

• Significant weight reduction
• Approved for obesity management (Zepbound)

SURPASS Trials (Diabetes):

• Superior HbA1c reduction vs insulin and GLP-1 agents
• Substantial weight loss

SURMOUNT Trials (Obesity):

• ~20% or greater body weight reduction in many patients
• Among the most effective pharmacologic weight-loss therapies to date

Tirzepatide improves:

• Blood pressure
• Lipid profile
• Visceral adiposity
• Inflammatory markers

Cardiovascular outcome trials are ongoing.

→ Cardiovascular Pharmacology

• Once-weekly subcutaneous injection
• Gradual titration recommended to reduce GI side effects

Common:

• Nausea
• Vomiting
• Diarrhea
• Early satiety

Serious (rare):

• Pancreatitis
• Gallbladder disease
• Risk of medullary thyroid carcinoma (boxed warning class effect)

• Personal or family history of medullary thyroid carcinoma
• MEN2 syndrome

Use caution in:

• History of pancreatitis

Compared to:

• Semaglutide
• Dulaglutide
• Liraglutide

Tirzepatide:

• Greater average weight loss
• Greater HbA1c reduction
• Similar GI adverse effects
• Expanding cardiovascular data

• First dual GLP-1/GIP agonist
• Among the most potent weight-loss medications available
• Low hypoglycemia risk unless combined with insulin
• Cardiovascular outcomes still under investigation
• Weekly injection

• Dual Incretin Agonists
• GLP-1 Receptor Agonists
• SGLT2 Inhibitors
• Heart Failure Module