Semaglutide
Ozempic / Wegovy / Rybelsus
Manufactured by Novo Nordisk · Subcutaneous injection (Ozempic, Wegovy) or Oral tablet (Rybelsus)
Avg Weight Loss
~15% body weight over 68 weeks (Wegovy 2
Dosing
Once weekly (injection) or Once daily (oral)
Brand Cost
$900-1,400
Compounded
$150-450
How It Works
Semaglutide mimics the naturally occurring hormone GLP-1, binding to GLP-1 receptors in the pancreas to stimulate insulin secretion and suppress glucagon release in a glucose-dependent manner. It also slows gastric emptying and acts on hypothalamic receptors to reduce appetite and food intake, leading to significant weight loss.
Dosing & Titration
ozempic
wegovy
rybelsus
Titration Protocol
Wegovy: Start at 0.25mg weekly for 4 weeks, increase to 0.5mg for 4 weeks, then 1mg for 4 weeks, then 1.7mg for 4 weeks, then maintenance dose of 2.4mg weekly. Ozempic: Start at 0.25mg weekly for 4 weeks, increase to 0.5mg, may increase to 1mg or 2mg after at least 4 weeks. Rybelsus: Start at 3mg daily for 30 days, increase to 7mg, may increase to 14mg after at least 30 days.
Common Side Effects
Serious Risks
Pancreatitis (rare)
Thyroid C-cell tumors (observed in rodent studies; relevance to humans unknown)
Gallbladder disease including cholelithiasis
Acute kidney injury (usually secondary to dehydration from GI side effects)
Diabetic retinopathy complications (in patients with existing retinopathy)
Hypoglycemia (when used with insulin or sulfonylureas)
Suicidal ideation (under FDA investigation, no causal link established)
Cost Comparison
Brand Name
$900-1,400
per month
Compounded
$150-450
per month
Oral
$900-1,000
per month
Insurance Coverage
Often covered for Type 2 Diabetes (Ozempic). Coverage for weight management (Wegovy) varies widely by plan; many commercial plans now cover it but Medicare Part D does not cover weight loss medications. Prior authorization typically required.
Pros & Cons
Advantages
- Once-weekly dosing (injection)
- Extensive long-term safety data
- Oral formulation available (Rybelsus)
- Proven cardiovascular benefit (SELECT trial)
- Multiple FDA-approved indications
- Most widely studied GLP-1 RA for weight management
Disadvantages
- GI side effects common during titration
- Injection required for weight loss doses
- Ongoing supply constraints
- High cost without insurance
- Weight regain common after discontinuation
Clinical Evidence
Clinical Trial Programs
STEP program (weight management: STEP 1-5, SELECT cardiovascular outcomes trial), SUSTAIN program (Type 2 Diabetes: SUSTAIN 1-10), PIONEER program (oral semaglutide: PIONEER 1-10)
step1
16.9% average weight loss vs 2.4% placebo over 68 weeks
select
20% reduction in major adverse cardiovascular events (MACE) in overweight/obese adults without diabetes
sustain6
26% reduction in MACE in Type 2 Diabetes patients
Contraindications
- Personal or family history of medullary thyroid carcinoma (MTC)
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- Known hypersensitivity to semaglutide or any excipients
- History of serious hypersensitivity reaction to semaglutide
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