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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

Frequently Asked Questions

How much weight can you lose on semaglutide? ▾
In the STEP 1 trial, semaglutide 2.4 mg/week produced an average 14.9% body weight loss over 68 weeks versus 2.4% for placebo. Approximately 32% of participants lost ≥20% of body weight. Results vary significantly based on adherence, baseline BMI, and diet.
What is the difference between semaglutide and Ozempic? ▾
Ozempic IS semaglutide — it is the brand name for the 0.5–2 mg/week injectable formulation approved for type 2 diabetes. Wegovy is the 2.4 mg/week formulation approved specifically for chronic weight management. Rybelsus is the oral tablet form. All three contain semaglutide as the active compound.
What are the most common semaglutide side effects? ▾
GI effects dominate: nausea (44%), diarrhea (30%), vomiting (24%), and constipation (24%) — most common during dose escalation and typically transient. More serious but rare risks include pancreatitis, gallbladder disease, and a theoretical thyroid C-cell tumor risk (black box warning based on rodent data).
How long does semaglutide take to work for weight loss? ▾
Most patients see initial weight loss within 4–8 weeks of starting. Maximum effect typically requires the full dose escalation period (12–16 weeks to reach 2.4 mg). Significant and sustained weight loss is most reliably seen after 16–20 weeks of consistent use at therapeutic dose.
Can you compound semaglutide? ▾
503A compounding pharmacies could legally compound semaglutide while it was on the FDA drug shortage list (through 2024–2025). As of early 2025, FDA declared the shortage resolved, triggering enforcement against most compounded semaglutide. 503B outsourcing facilities have additional compliance requirements. The legal landscape continues to evolve.

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.

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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

Related Peptides

TirzepatideLiraglutideExenatideCagrilintideRetatrutide

Used For

›Cardiovascular Health ›Obesity & Weight Loss

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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.