====== 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)

→ [[endocrine:glp1:start|GLP-1 Receptor Agonists Overview]]

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===== 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.

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===== Indications =====

==== Type 2 Diabetes Mellitus ====

• Glycemic control
• Cardiovascular risk reduction

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==== Obesity ★ ====

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

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==== Atherosclerotic Cardiovascular Disease (ASCVD) ★ ====

Semaglutide reduces:

  * • Myocardial infarction  
  * • Stroke  
  * • Cardiovascular death  

Particularly beneficial in patients with established ASCVD.

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

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===== 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

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===== Dosing Forms =====

Injectable (weekly):
  * • Ozempic
  * • Wegovy (higher obesity dose)

Oral (daily):
  * • Rybelsus

Oral formulation requires:
  * • Empty stomach
  * • Limited water
  * • No food for 30 minutes

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===== 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.

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===== Contraindications =====

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

Use caution in:

  * • History of pancreatitis  

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===== Semaglutide vs Other GLP-1 Agents =====

[[endocrine:glp1:exenatide|Exenatide]]:
  * • Shorter acting
  * • Less weight loss

[[endocrine:glp1:liraglutide|Liraglutide]]:
  * • Daily injection
  * • Proven ASCVD benefit

[[endocrine:glp1:dulaglutide|Dulaglutide]]:
  * • Weekly injection
  * • Strong ASCVD benefit

Semaglutide:
  * • Strongest weight loss among GLP-1 RAs
  * • Strong ASCVD reduction
  * • Available oral formulation

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===== GLP-1 vs SGLT2 in Cardiovascular Disease =====

Semaglutide:

  * • Strong ASCVD reduction
  * • Weight loss dominant

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

  * • Strong heart failure benefit
  * • Strong renal protection

These classes are often combined in cardiometabolic patients.

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===== 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  

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Related:

→ [[endocrine:glp1:start|GLP-1 Receptor Agonists]]
→ [[endocrine:sglt2:start|SGLT2 Inhibitors]]
→ [[cardio:heart_failure:start|Heart Failure Module]]
→ [[cardio:intro:start|Cardiovascular Modules]]