====== Exenatide ======

Exenatide was the first FDA-approved GLP-1 receptor agonist (2005) for Type 2 Diabetes.

Brand names:
  * Byetta (twice daily)
  * Bydureon (once weekly extended-release)

→ [[endocrine:glp1:start|GLP-1 Receptor Agonists Overview]]

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

Exenatide activates the GLP-1 receptor.

Effects:

  * Increases glucose-dependent insulin secretion
  * Decreases glucagon secretion
  * Slows gastric emptying
  * Increases satiety
  * Promotes weight loss

Because insulin release is glucose-dependent, hypoglycemia risk is low unless combined with insulin or sulfonylureas.

===== Indications =====

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

  * Glycemic control
  * Weight reduction

Exenatide is not primarily used for obesity-only treatment.

===== Cardiovascular Effects =====

EXSCEL Trial:

  * Demonstrated cardiovascular safety
  * Did NOT show strong mortality reduction compared to later GLP-1 agents

Compared to:

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

Exenatide has weaker cardiovascular outcome data.

===== Dosing =====

Byetta:
  * Twice-daily injection before meals

Bydureon:
  * Once-weekly extended-release injection

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

Common:

  * Nausea
  * Vomiting
  * Diarrhea
  * Early satiety

Serious (rare):

  * Pancreatitis
  * Gallbladder disease

More GI side effects than newer agents.

===== Contraindications =====

  * Severe renal impairment (especially short-acting formulation)
  * History of pancreatitis (use caution)

===== Exenatide vs Newer GLP-1 Agents =====

Exenatide:

  * First-in-class
  * More GI side effects
  * Less robust ASCVD data
  * Shorter half-life (Byetta)

[[endocrine:glp1:liraglutide|Liraglutide]]:

  * Proven mortality benefit

[[endocrine:glp1:semaglutide|Semaglutide]]:

  * Strongest weight loss
  * Strong ASCVD reduction

[[endocrine:glp1:dulaglutide|Dulaglutide]]:

  * Weekly dosing
  * Strong primary prevention data

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

  * First GLP-1 receptor agonist
  * More GI intolerance
  * Twice-daily option available
  * Cardiovascular safety demonstrated but limited superiority data
  * Largely replaced by newer GLP-1 agents

===== Related =====

  * [[endocrine:glp1:start|GLP-1 Receptor Agonists]]
  * [[endocrine:sglt2:start|SGLT2 Inhibitors]]
  * [[cardio:intro:start|Cardiovascular Modules]]