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)

→ GLP-1 Receptor Agonists Overview

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.

• Glycemic control
• Weight reduction

Exenatide is not primarily used for obesity-only treatment.

EXSCEL Trial:

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

Compared to:

• Liraglutide
• Semaglutide
• Dulaglutide

Exenatide has weaker cardiovascular outcome data.

Byetta:

• Twice-daily injection before meals

Bydureon:

• Once-weekly extended-release injection

Common:

• Nausea
• Vomiting
• Diarrhea
• Early satiety

Serious (rare):

• Pancreatitis
• Gallbladder disease

More GI side effects than newer agents.

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

Exenatide:

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

Liraglutide:

• Proven mortality benefit

Semaglutide:

• Strongest weight loss
• Strong ASCVD reduction

Dulaglutide:

• Weekly dosing
• Strong primary prevention data

• 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

• GLP-1 Receptor Agonists
• SGLT2 Inhibitors
• Cardiovascular Modules