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Semaglutide
Semaglutide is a long-acting GLP-1 receptor agonist used for Type 2 Diabetes, obesity, and cardiovascular risk reduction.
Brand names:
- • Ozempic (Type 2 Diabetes)
- • Wegovy (Obesity)
- • Rybelsus (Oral formulation)
→ GLP-1 Receptor Agonists Overview
Mechanism of Action
Semaglutide activates the GLP-1 receptor.
Effects:
- • ↑ Glucose-dependent insulin secretion
- • ↓ Glucagon secretion
- • Slows gastric emptying
- • ↑ Satiety
- • Promotes significant weight loss
Net effects:
- • ↓ HbA1c
- • ↓ Body weight
- • ↓ Major adverse cardiovascular events
Low hypoglycemia risk unless combined with insulin or sulfonylureas.
Indications
Type 2 Diabetes Mellitus
• Glycemic control • Cardiovascular risk reduction
Obesity ★
- • Significant weight loss
- • Reduction in visceral adiposity
- • Improves cardiometabolic profile
Atherosclerotic Cardiovascular Disease (ASCVD) ★
Semaglutide reduces:
- • Myocardial infarction
- • Stroke
- • Cardiovascular death
Particularly beneficial in patients with established ASCVD.
Major Trials
SUSTAIN-6:
• Reduced major adverse cardiovascular events
STEP trials:
• Significant weight reduction
SELECT trial:
• Cardiovascular event reduction in overweight/obese patients without diabetes
Dosing Forms
Injectable (weekly):
- • Ozempic
- • Wegovy (higher obesity dose)
Oral (daily):
- • Rybelsus
Oral formulation requires:
- • Empty stomach
- • Limited water
- • No food for 30 minutes
Adverse Effects
Common:
- • Nausea
- • Vomiting
- • Diarrhea
- • Early satiety
Serious (rare):
- • Pancreatitis
- • Gallbladder disease
- • Theoretical risk of medullary thyroid carcinoma
Weight loss may increase gallstone risk.
Contraindications
• Personal or family history of medullary thyroid carcinoma • MEN2 syndrome • Severe GI disease
Use caution in:
• History of pancreatitis
Semaglutide vs Other GLP-1 Agents
Exenatide: • Shorter acting • Less weight loss
Liraglutide: • Daily injection • Proven ASCVD benefit
Dulaglutide: • Weekly injection • Strong ASCVD benefit
Semaglutide: • Strongest weight loss among GLP-1 RAs • Strong ASCVD reduction • Available oral formulation
GLP-1 vs SGLT2 in Cardiovascular Disease
Semaglutide:
• Strong ASCVD reduction • Weight loss dominant
• Strong heart failure benefit • Strong renal protection
These classes are often combined in cardiometabolic patients.
Clinical Pearls
✔ Weekly or oral option ✔ Powerful weight loss ✔ Reduces ASCVD events ✔ Low hypoglycemia risk ✔ Not a core heart failure therapy ✔ Monitor for GI intolerance
Related:
→ GLP-1 Receptor Agonists → SGLT2 Inhibitors → Heart Failure Module → Cardiovascular Modules