Semaglutide
moderate riskAlso: Ozempic · Wegovy · Rybelsus
Semaglutide is an FDA-approved GLP-1 receptor agonist with the strongest clinical evidence of any peptide on the market. STEP trials: 15–17% body weight reduction. SELECT trial: 20% cardiovascular risk reduction in non-diabetic overweight patients. The defining weight-loss drug of the 2020s.
Reported Benefits
Weight loss
STEP 1: 14.9% body weight loss at 68 weeks vs. 2.4% placebo.
Glycemic control
SUSTAIN program: HbA1c reduction 1.5–1.8 percentage points vs. placebo.
Cardiovascular risk reduction
SUSTAIN-6 and SELECT trials: significant MACE reduction including in non-diabetic patients.
Mechanism of Action
GLP-1 receptor agonist — enhances glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, reduces appetite via hypothalamic signaling.
Key Clinical Studies
The Evidence Gold Standard
Semaglutide has more rigorous, large-scale human evidence than any other peptide in this database. The SELECT trial expanding indication to non-diabetic cardiovascular risk reduction marks a paradigm shift in obesity treatment.
Compounding History
Compounded semaglutide was temporarily legal during the FDA shortage (2022–2024). The shortage was resolved; compounding is now federally prohibited. FDA enforcement actions are ongoing.
Regulatory Status
FDA ApprovedFDA approved — Ozempic (T2D), Wegovy (obesity), Rybelsus (oral T2D)
Safety Profile
Side Effects
- •Nausea
- •Vomiting
- •Diarrhea
- •Constipation
- •Pancreatitis (rare)
- •Thyroid C-cell tumors (black box, animal data)
Contraindications
- •MTC/MEN2 history
- •Pregnancy
Drug Interactions
- •Oral medications (gastric emptying delay)
- •Insulin/sulfonylureas (hypoglycemia)
Primary Uses
Related Peptides
Weekly Briefing
Regulatory updates + new study breakdowns.
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