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

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.

• Glycemic control • Cardiovascular risk reduction

• • Significant weight loss
• • Reduction in visceral adiposity
• • Improves cardiometabolic profile

Semaglutide reduces:

• • Myocardial infarction
• • Stroke
• • Cardiovascular death

Particularly beneficial in patients with established ASCVD.

→ Cardiovascular Modules

SUSTAIN-6:

• Reduced major adverse cardiovascular events

STEP trials:

• Significant weight reduction

SELECT trial:

• Cardiovascular event reduction in overweight/obese patients without diabetes

Injectable (weekly):

• • Ozempic
• • Wegovy (higher obesity dose)

Oral (daily):

• • Rybelsus

Oral formulation requires:

• • Empty stomach
• • Limited water
• • No food for 30 minutes

Common:

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

Serious (rare):

• • Pancreatitis
• • Gallbladder disease
• • Theoretical risk of medullary thyroid carcinoma

Weight loss may increase gallstone risk.

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

Use caution in:

• • History of pancreatitis

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

Semaglutide:

• • Strong ASCVD reduction
• • Weight loss dominant

SGLT2 Inhibitors:

• • Strong heart failure benefit
• • Strong renal protection

These classes are often combined in cardiometabolic patients.

• ✔ 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