====== GLP-1 Receptor Agonists ======

GLP-1 receptor agonists are incretin-based therapies that enhance glucose-dependent insulin secretion and promote weight loss.

They are foundational agents in:

• Type 2 Diabetes Mellitus
• Obesity
• Atherosclerotic Cardiovascular Disease (ASCVD)

Unlike [[endocrine:sglt2:start|SGLT2 Inhibitors]], GLP-1 receptor agonists primarily reduce atherosclerotic cardiovascular events rather than heart failure hospitalization.

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

GLP-1 (Glucagon-Like Peptide-1) is an incretin hormone released after meals.

GLP-1 receptor agonists:

• Increase glucose-dependent insulin secretion  
• Decrease glucagon secretion  
• Slow gastric emptying  
• Increase satiety  
• Promote weight loss  

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

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===== FDA-Approved GLP-1 Receptor Agonists (Chronologic Order) =====

  * • [[endocrine:glp1:exenatide|Exenatide]] (2005)  
  * • [[endocrine:glp1:liraglutide|Liraglutide]] (2010)  
  * • [[endocrine:glp1:dulaglutide|Dulaglutide]] (2014)  
  * • [[endocrine:glp1:semaglutide|Semaglutide]] (2017 injectable; 2019 oral)  

Each agent differs in half-life, dosing frequency, and cardiovascular outcome data.

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

GLP-1 receptor agonists reduce:

  * • Myocardial infarction  
  * • Stroke  
  * • Cardiovascular death  

Strongest ASCVD data:

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

They are particularly beneficial in patients with established ASCVD.

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

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===== What GLP-1 Agents Do NOT Primarily Treat =====

• They are NOT core therapies for heart failure.
• They do NOT significantly reduce HF hospitalization compared to SGLT2 inhibitors.

For heart failure benefit:

→ [[endocrine:sglt2:start|SGLT2 Inhibitors]]

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

Common:

  * • Nausea  
  * • Vomiting  
  * • Diarrhea  
  * • Early satiety  

Serious (rare):

  * • Pancreatitis  
  * • Gallbladder disease  
  * • Medullary thyroid carcinoma risk (avoid in MEN2)  

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===== Contraindications =====

• Personal or family history of medullary thyroid carcinoma  
• MEN2 syndrome  
• Severe gastrointestinal disease  

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===== GLP-1 vs SGLT2 =====

GLP-1 receptor agonists:

  * • Strong weight loss  
  * • Strong ASCVD reduction  
  * • Minimal HF benefit  

[[endocrine:sglt2:start|SGLT2 Inhibitors]]:

  * • Strong HF benefit  
  * • Strong CKD protection  
  * • Mild weight loss  

These classes are often complementary in cardiometabolic disease.

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

  * ✔ Glucose-dependent insulin release  
  * ✔ Promote weight loss  
  * ✔ Reduce ASCVD events  
  * ✔ Low hypoglycemia risk  
  * ✔ Not primary HF therapy  
  * ✔ Complementary to SGLT2 inhibitors  

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Related:

→ [[endocrine:sglt2:start|SGLT2 Inhibitors]]  
→ [[cardio:heart_failure:start|Heart Failure Module]]  
→ [[cardio:intro:start|Cardiovascular Modules]]  
→ [[endocrine:start|Endocrine Pharmacology]]