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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.
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.
FDA-Approved GLP-1 Receptor Agonists (Chronologic Order)
- • Exenatide (2005)
- • Liraglutide (2010)
- • Dulaglutide (2014)
- • Semaglutide (2017 injectable; 2019 oral)
Each agent differs in half-life, dosing frequency, and cardiovascular outcome data.
Cardiovascular Effects
GLP-1 receptor agonists reduce:
- • Myocardial infarction
- • Stroke
- • Cardiovascular death
Strongest ASCVD data:
They are particularly beneficial in patients with established ASCVD.
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:
Adverse Effects
Common:
- • Nausea
- • Vomiting
- • Diarrhea
- • Early satiety
Serious (rare):
- • Pancreatitis
- • Gallbladder disease
- • Medullary thyroid carcinoma risk (avoid in MEN2)
Contraindications
• Personal or family history of medullary thyroid carcinoma • MEN2 syndrome • Severe gastrointestinal disease
GLP-1 vs SGLT2
GLP-1 receptor agonists:
• Strong weight loss • Strong ASCVD reduction • Minimal HF benefit
• Strong HF benefit • Strong CKD protection • Mild weight loss
These classes are often complementary in cardiometabolic disease.
Clinical Pearls
✔ 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