====== 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)

→ [[endocrine:glp1_gip:dual_glp-1_gip_incretin_agonists|Dual GLP-1/GIP Incretin Agonists]]

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===== Mechanism of Action =====

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.

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===== Indications =====

==== Type 2 Diabetes Mellitus ====

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

==== Obesity / Chronic Weight Management ★ ====

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

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===== Clinical Trials =====

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

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===== Cardiometabolic Effects =====

Tirzepatide improves:

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

Cardiovascular outcome trials are ongoing.

→ [[cardio:intro:start|Cardiovascular Pharmacology]]

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===== Dosing =====

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

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

Common:

  * Nausea
  * Vomiting
  * Diarrhea
  * Early satiety

Serious (rare):

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

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===== Contraindications =====

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

Use caution in:

  * History of pancreatitis

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===== Tirzepatide vs GLP-1 Receptor Agonists =====

Compared to:

  * [[endocrine:glp1:semaglutide|Semaglutide]]
  * [[endocrine:glp1:dulaglutide|Dulaglutide]]
  * [[endocrine:glp1:liraglutide|Liraglutide]]

Tirzepatide:

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

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===== Clinical Pearls =====

  * 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

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===== Related =====

  * [[endocrine:glp1_gip:dual_glp-1_gip_incretin_agonists|Dual Incretin Agonists]]
  * [[endocrine:glp1:start|GLP-1 Receptor Agonists]]
  * [[endocrine:sglt2:start|SGLT2 Inhibitors]]
  * [[cardio:heart_failure:start|Heart Failure Module]]