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 SGLT2 Inhibitors, GLP-1 receptor agonists primarily reduce atherosclerotic cardiovascular events rather than heart failure hospitalization.

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.

• • Exenatide (2005)
• • Liraglutide (2010)
• • Dulaglutide (2014)
• • Semaglutide (2017 injectable; 2019 oral)

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

GLP-1 receptor agonists reduce:

• • Myocardial infarction
• • Stroke
• • Cardiovascular death

Strongest ASCVD data:

• • Liraglutide
• • Semaglutide
• • Dulaglutide

They are particularly beneficial in patients with established ASCVD.

→ Cardiovascular Modules

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

For heart failure benefit:

→ SGLT2 Inhibitors

Common:

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

Serious (rare):

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

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

GLP-1 receptor agonists:

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

SGLT2 Inhibitors:

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

These classes are often complementary in cardiometabolic disease.

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

Related:

→ SGLT2 Inhibitors → Heart Failure Module → Cardiovascular Modules → Endocrine Pharmacology