Semaglutide

Ozempic · Wegovy · Rybelsus (approved medicine)

Metabolic & weight

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Semaglutide is an approved prescription medicine in most countries, not a research-only compound. This page explains the published science. Use outside a prescription — including compounded or grey-market versions — carries real risks discussed below.

1What it is

Semaglutide is a modified copy of GLP-1, a hormone your gut releases after eating. Natural GLP-1 lasts about two minutes in the blood; semaglutide’s modifications let a single injection last a week.

It was approved for type 2 diabetes in 2017 and for weight management in 2021, and has since become one of the most prescribed medicines in the world.

2How it's thought to work

Pancreas. More insulin and less glucagon, glucose-dependently — on its own it rarely causes low blood sugar.

Stomach. Slows gastric emptying, increasing fullness (weakens over months).

Brain. Acts on appetite centres to reduce hunger.

Heart and vessels. Reduces cardiovascular events beyond weight loss alone.

GLP-1 receptor activation: more insulin from the pancreas, slower stomach emptying, stronger fullness signals in the brain. A fatty-acid chain lets the peptide ride on albumin, so one injection lasts a week.Schematic — not to scale

3What the research shows

Weight loss in people with obesity

STEP 1 (n≈1,961): mean weight change −14.9% vs −2.4% with placebo at 68 weeks on 2.4 mg weekly. About two-thirds of lost weight regained within a year off treatment. [1][2]

Type 2 diabetes glucose control

SUSTAIN 1–7: HbA1c reductions of roughly 1.5–1.8 percentage points. [3]

Cardiovascular outcomes

SELECT (n≈17,600): 20% relative reduction in major adverse cardiovascular events over ~3.3 years. [4]

Kidney disease

FLOW: 24% reduction in major kidney-disease events in type 2 diabetes with CKD. [5]

Alcohol use, addiction, dementia

Observational signals and small trials; Alzheimer’s trials did not meet their primary endpoint in 2025.

4Reported side effects and interactions

Literature-reported

Nausea (up to ~44% in STEP 1), diarrhoea, vomiting, constipation, abdominal pain — mostly during titration. Warnings: gallbladder disease, pancreatitis (rare), retinopathy complications, thyroid C-cell tumour boxed warning (rodent), aspiration risk under anaesthesia.

Community-reported

Fatigue, food aversion, constipation; reports of unit confusion with compounded vials.

Interactions. Increased hypoglycaemia risk with insulin or sulfonylureas; slowed absorption of oral medicines; not for use in pregnancy.

Markers researchers commonly monitor

Marker	Why it's watched
HbA1c, fasting glucose	Glucose-lowering effect; hypoglycaemia risk with other medicines
Lipase / amylase	Pancreatitis signal
Lipid panel	Cardiometabolic tracking
eGFR, creatinine	Dehydration from GI side effects can affect kidneys

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Approved pens need no . vials require careful maths: doses are in milligrams, concentrations are often high, and volumes per dose are small. Double-check units.

Open in calculator, pre-loaded →

6Commonly studied alongside

Cagrilintide →CagriSema combination is in Phase 3 Tirzepatide →As a comparator, not together

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	FDA-approved. Shortage resolved early 2025; routine compounding no longer permitted
European Union	EMA-authorised
United Kingdom	MHRA-licensed; prescription-only
Australia	TGA-approved; compounding of GLP-1 copies banned from Oct 2024
South Africa	SAHPRA-registered; prescription-only
Canada	Health Canada-approved
Sport	Not prohibited by WADA (as of review date)

8Open questions

Optimal duration and whether lower maintenance doses hold weight.
Long-term effects on muscle, bone and the gallbladder.
Mechanism of cardiovascular and kidney benefit beyond weight.

9References

1Wilding JPH et al. (2021). Once-weekly semaglutide in adults with overweight or obesity (STEP 1). NEJM. PubMed · DOI
2Wilding JPH et al. (2022). Weight regain after withdrawal of semaglutide. Diabetes Obes Metab. PubMed
3Marso SP et al. (2016). SUSTAIN-6. NEJM. PubMed
4Lincoff AM et al. (2023). SELECT. NEJM. PubMed
5Perkovic V et al. (2024). FLOW. NEJM. PubMed
6Kosiborod MN et al. (2023). STEP-HFpEF. NEJM. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

10Community

forum threads →

community protocols include this →

Threads and protocols are visible to members. Joining is free.

Self-reported side effects Phase 2

Self-reported by 412 members who logged this compound for 4+ weeks. This is what people logged, not how often it happens.

Nausea, week 1–2

41%

Appetite change

63%

Constipation

22%

Fatigue

18%

Injection-site redness

11Page history

11 Oct 2026ESSENCE (MASH) result added

10 Jun 2026Page published

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