Fat loss
Semaglutide
Long-acting GLP-1 receptor agonist that kicked off the modern GLP-1 weight-loss era. FDA-approved for type 2 diabetes and chronic weight management.
FDA-approved Fat loss
- Full name
- Semaglutide (GLP-1 receptor agonist)
- Also known as
- Ozempic (diabetes brand), Wegovy (weight-loss brand), Rybelsus (oral brand)
- Regulatory status
- FDA-approved prescription medication (Ozempic for type 2 diabetes, Wegovy for chronic weight management, Rybelsus as an oral tablet). Widely available by prescription; also present in the grey/compounded market, which carries additional quality-control risk.
Origin
A synthetic analog of human GLP-1, modified with a fatty-acid side chain that binds albumin, extending its half-life from the native hormone's few minutes to about a week and allowing once-weekly injection.
Mechanism
Activates GLP-1 receptors in the pancreas (glucose-dependent insulin secretion, glucagon suppression), the brain (appetite suppression via hypothalamic and brainstem centers, reduced food reward), and the gut (delayed gastric emptying, longer satiety after meals).
Research summary
Evidence
One of the most rigorously studied drugs in this wiki: large RCTs (STEP for weight loss, SUSTAIN for diabetes) enrolling thousands of patients. STEP trials showed average weight loss around 15% of body weight over 68 weeks in non-diabetic participants at the 2.4 mg/week dose, versus roughly 2-3% with placebo. The SELECT cardiovascular outcomes trial showed fewer major adverse cardiovascular events in overweight/obese patients with existing cardiovascular disease. Long-term data beyond a few years is still accumulating, and weight regain after stopping is well documented: most trial participants regained a substantial portion of lost weight within a year of stopping.
Evidence tier: FDA-approved — see the methodology note for how this is assessed.
Citations
- Once-Weekly Semaglutide in Adults with Overweight or Obesity — Wilding et al. 2021
- Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension — Wilding et al. 2022
- Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program — Perreault et al. 2022
- Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5 — Kushner et al. 2020
Reported benefits
- Substantial, well-documented weight loss in clinical trial populations
- Improved glycemic control in type 2 diabetes
- Reduced cardiovascular event risk in at-risk patients (per SELECT trial)
- Reported reduction in 'food noise' / compulsive eating thoughts, widely discussed in user communities
Dosing protocols reported in the literature & community
These are protocols reported by compounding pharmacies, published trials, or self-experimentation communities — not a prescription. Start low, especially for anything new.
| Route | Reported protocol |
|---|---|
| Subcutaneous injection, once weekly (standard prescribed titration) | Standard titration starts at 0.25 mg/week for 4 weeks, then increases roughly every 4 weeks (0.5 mg → 1 mg → 1.7 mg → 2.4 mg for Wegovy) to reduce GI side effects; maintenance dose depends on indication and tolerability. |
Side effects
- Nausea, vomiting, diarrhea or constipation, especially during dose escalation — the most common reason people stop
- Rare but serious: pancreatitis, gallbladder disease, risk of thyroid C-cell tumors (boxed warning based on rodent data; human relevance unconfirmed but the warning stands)
- Loss of lean muscle mass alongside fat mass is a well-documented concern, making resistance training and adequate protein intake important during treatment
- Not recommended in personal/family history of medullary thyroid carcinoma or MEN 2 syndrome
Safety notes
Community & reddit notes (anecdotal — not clinical evidence)
The most widely discussed weight-loss peptide by a wide margin. Community reporting consistently points to 'food noise' reduction as the most distinctive subjective effect, more than simply feeling less hungry. Slow dose titration to manage nausea, plus strength training and protein intake to preserve muscle during the cut, come up constantly. Weight regain after stopping is a recurring topic; many long-term users treat it as ongoing maintenance rather than a finite course.
Related peptides
Used in stacks
Community combinations that include Semaglutide — see each stack page for the combination-specific rationale and evidence.
Mixing compatibility
Pulled from a community-charted mixing-compatibility reference (anecdotal, clinic-use, and community-reported signals) — not a safety guarantee. Verify independently before combining anything.