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Semaglutide

moderate risk

Also: Ozempic · Wegovy · Rybelsus

Strong Evidence FDA Approved

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.

Molecular Weight
4113.6 Da
Formula
C187H291N45O59
Common Dosing
0.25–2.4 mg/week SC (Wegovy); 3–14 mg/day oral (Rybelsus); 0.5–2 mg/week (Ozempic)
Category
therapeutic
Last Reviewed
2025-01-15

Reported Benefits

Weight loss

Strong Evidence 156 studies

STEP 1: 14.9% body weight loss at 68 weeks vs. 2.4% placebo.

Glycemic control

Strong Evidence 200 studies

SUSTAIN program: HbA1c reduction 1.5–1.8 percentage points vs. placebo.

Cardiovascular risk reduction

Strong Evidence 89 studies

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

Wilding et al. (STEP 1) (2021)

Phase III RCT · n=1961

PubMed →

14.9% weight loss at 68 weeks

Ryan et al. (SELECT) (2024)

Phase III RCT · n=17604

PubMed →

20% reduction in cardiovascular events in non-diabetic overweight patients

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 Approved

FDA 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

Type 2 diabetesObesity/weight lossCardiovascular risk reduction

Weekly Briefing

Regulatory updates + new study breakdowns.

For Practitioners

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Disclaimer: This information is for educational and research purposes only. Not medical advice. Consult a qualified healthcare provider before using any compound.