Reviewed & approved by Dr. Nova Reyes · Last checked 2026-10-15. ← Back to Evidence Library

Semaglutide: what the evidence says

Legend: HUMAN data · ANIMAL / LAB data · UNKNOWN · UNVERIFIED: not yet confirmed against a primary source

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What is it?

Semaglutide is a GLP-1 receptor agonist, meaning it switches on the same receptors as the GLP-1 hormone. It acts like a gut hormone that tells the pancreas to release insulin after meals. It also slows the stomach and reduces appetite. It is taken once a week by injection or once a day as a tablet. ^R7

The FDA has approved it for: ^R7 - Ozempic (injection): blood-sugar control in adults with type 2 diabetes; lowering the risk of heart attack, stroke and heart death in adults with type 2 diabetes and heart disease; and lowering the risk of kidney decline and heart death in adults with type 2 diabetes and chronic kidney disease. - Rybelsus / Ozempic tablets: blood-sugar control in adults with type 2 diabetes, and lowering heart risk in those at high risk. - Wegovy (injection and tablets): long-term weight management in adults (and, for the injection, teens 12+ with obesity); lowering heart risk in adults with heart disease and obesity or overweight. The injection is also approved for a type of fatty-liver disease (MASH) with moderate to advanced scarring. This is an accelerated approval: approved early, based on a promising early result, with confirmation trials still required.

Does it work?

Human Weight: in STEP 1, adults with obesity or overweight (without diabetes) on semaglutide (study arm in the study table) lost about 14.9% of body weight over 68 weeks, vs 2.4% on placebo. ^R2

Human Heart risk: in SUSTAIN-6 (type 2 diabetes), heart attack, stroke or heart death happened in 6.6% on semaglutide vs 8.9% on placebo (a dummy treatment). In SELECT (heart disease and overweight, no diabetes), it was 6.5% vs 8.0%. The tablet form (PIONEER 6) was shown to be at least as safe for the heart as placebo. ^R2

Is it safe?

Its safety profile is well studied for the approved products, used as labeled. The FDA labels warn about: ^R4 - Caution Boxed warning, thyroid C-cell tumors: semaglutide caused thyroid C-cell tumors in rodents. Whether it does in people is unknown. Don't use it with a personal or family history of medullary thyroid cancer (MTC) or MEN 2. Watch for a neck lump, trouble swallowing, shortness of breath or lasting hoarseness. - Caution Pancreatitis: seen with GLP-1 drugs including semaglutide. Severe stomach pain, sometimes spreading to the back, with or without vomiting, needs urgent care. - Caution Gallbladder disease: gallstones and gallbladder problems happened in trials. - Caution Also on the label: low blood sugar (mainly with insulin or sulfonylureas), kidney injury from dehydration, severe stomach side effects, and others. Human In SUSTAIN-6, diabetic eye (retinopathy) complications were more common on semaglutide. ^{R2, R4} - Caution More people on semaglutide than on placebo stopped early because of side effects: 16.6% vs 8.2% in SELECT (PMID 37952131). ^R2

Compounded and gray-market semaglutide: extra risks

This is where people are getting hurt right now: FDA has received 990 adverse event reports for compounded semaglutide and has issued alerts about dosing errors. ^{R9, R10}

• Overdoses from measuring mistakes. The FDA has received reports of adverse events (problems reported after use, which may or may not have been caused by the drug), some needing hospitalization. They may be related to overdoses from dosing errors with compounded semaglutide in multi-dose vials. Most reports described patients drawing up too much, in those cases 5 to 20 times the intended dose. Reported harms included nausea, vomiting, stomach pain, fainting, headache, migraine, dehydration, acute pancreatitis and gallstones. ^R9
• "Units" vs mg vs mL. Approved injectable products are dosed in milligrams. Vials come in different strengths and are often dosed in "units" on an insulin syringe. See below. ^R9
• Higher doses or faster increases than the label have also been linked to adverse event reports with compounded products. As of May 31, 2026, FDA had received 990 adverse event reports for compounded semaglutide, and it notes these are likely under-reported. ^R10
• Not FDA-reviewed. Compounded drugs don't undergo FDA premarket review for safety, quality or effectiveness. The FDA says salt forms (such as semaglutide sodium or acetate) should not be used to compound semaglutide. Gray-market "research" vials have even fewer checks. ^{R9, R10}

How unit mix-ups cause overdoses

1. "Units" are not mg. On an insulin syringe, "units" are marks for volume, not for the amount of drug. How much drug a unit holds depends entirely on how concentrated the vial is. ^R9

2. Mix-ups cause overdoses. FDA describes patients who drew up many times the intended amount, and prescribers who made errors converting mg into units. ^R9

3. Concentration isn't standard. Compounded and gray-market vials come in different strengths, and some are mixed by the user. The same mark on the syringe can deliver very different amounts of drug depending on the vial.

4. A long half-life makes mistakes last. Semaglutide lasts about a week in the body, so an overdose can need long observation and treatment. ^R9

What protects people (from FDA's alert): dose instructions written in mg, with the exact vial concentration and syringe type, and checked with the prescriber or pharmacist. Approved pens are dosed in mg with standard concentrations. ^R9

What we don't know

• Unknown What is actually in a given compounded or gray-market vial (strength, salt form, sterility)
• Unknown Whether the rodent thyroid tumor finding applies to people (per the label)
• Unknown Long-term outcomes of off-label or unsupervised use

Is it legal?

FDA-approved as a prescription drug for the uses above. Compounded versions are not FDA-approved. FDA declared the semaglutide injection shortage resolved on Feb 21, 2025. Its grace periods for compounding copies have ended. In April 2026, FDA also proposed removing semaglutide from the list that outsourcing facilities (large-scale compounders) can compound from. Semaglutide is not named on WADA's 2026 Prohibited List. As of Oct 15, 2026. ^{R7, R8, R10}

What's in the vial?

Pharmacy-dispensed Ozempic, Wegovy and Rybelsus are made under FDA oversight. Gray-market "semaglutide" is not. FDA warns that counterfeit versions could contain the wrong ingredients, too little, too much or no active ingredient, or other harmful ingredients, and that salt forms are being sold. In a small study, all 3 semaglutide vials bought from illegal online pharmacies held far more drug than labeled (about 29%–39% over), had low purity, and contained bacterial toxins (endotoxin). ^{R10, R11} Under the Open Peptide Standard, a GLP-1 vial overfilled by more than 20% is a critical fail (draft threshold). See results at /tests/. A passing test covers one batch, tested on one date. It does not mean the compound itself is safe.

What do users report?

Self-report, not evidence.

Unknown TBD. We'll only list this once we can cite a public source.

Study details

^R2 Human Human studies

All four trials were funded by Novo Nordisk, the maker.

Study	People	Route	Dose used	Follow-up	Reported	Limitations	Citation
STEP 1 (Wilding 2021), obesity/overweight without diabetes	1,961 (randomized 2:1)	Subcutaneous	2.4 mg weekly + lifestyle	68 wk	Weight −14.9% vs −2.4%; GI-related stopping 4.5% vs 0.8%	Sponsor-funded	PMID 33567185
SUSTAIN-6 (Marso 2016), T2D high CV risk	3,297	Subcutaneous	0.5 or 1.0 mg weekly	104 wk	MACE 6.6% vs 8.9% (HR 0.74); retinopathy complications higher (HR 1.76)	Designed for non-inferiority	PMID 27633186
SELECT (Lincoff 2023), CV disease + overweight, no diabetes	17,604	Subcutaneous	2.4 mg weekly	Mean follow-up 39.8 mo (mean exposure 34.2 mo)	MACE 6.5% vs 8.0% (HR 0.80); stopping 16.6% vs 8.2%	Sponsor-funded	PMID 37952131
PIONEER 6 (Husain 2019), T2D high CV risk	3,183	Oral	Once daily; Caution dose not in abstract [UNVERIFIED: 14 mg target]	Median 15.9 mo	MACE 3.8% vs 4.8% (HR 0.79, non-inferior; superiority not shown)	Non-inferiority design	PMID 31185157

^{R4, R7} Label and regulatory (as of Oct 15, 2026)

• Dosing: approved dosing for Ozempic, Rybelsus and Wegovy is set by each prescribing label; see the labels: Ozempic, Rybelsus, Wegovy (DailyMed). Rybelsus and Ozempic tablets are not interchangeable (label).
• ^R4 Boxed warning: risk of thyroid C-cell tumors; contraindicated with personal/family history of MTC or MEN 2. Warnings: acute pancreatitis ("Discontinue if pancreatitis is suspected"), acute gallbladder disease, hypoglycemia, acute kidney injury, severe GI reactions (all three labels above).

^{R9, R10} FDA compounding notices

• ^R9 FDA alerts health care providers, compounders and patients of dosing errors associated with compounded injectable semaglutide products (content current as of Jul 26, 2024).
• ^R10 FDA's concerns with unapproved GLP-1 drugs used for weight loss (content current as of Oct 1, 2026): salt forms; doses beyond the label; 990 compounded-semaglutide adverse event reports as of May 31, 2026.
• ^R10 Shortage and compounding: "[2/21/2025] FDA has determined the shortage of semaglutide injection products... is resolved." For 503A pharmacies, "the period of enforcement discretion... has ended" (503A grace period ran to Apr 22, 2025; 503B to May 22, 2025) (FDA statement, content current as of Apr 1, 2026). On Apr 30, 2026 FDA proposed excluding semaglutide from the 503B bulks list, with comments due Jun 29, 2026 (FDA press release), later extended to Jul 30, 2026 (Federal Register). UNVERIFIED Whether FDA has finalized the 503B exclusion: no final notice found.
• ^R10 Counterfeits: FDA warns that counterfeit products "could contain the wrong ingredients, contain too little, too much or no active ingredient at all or other harmful ingredients."
• ^R11 Online-purchase testing (semaglutide): Ashraf AR, et al. J Med Internet Res. 2024;26:e65440. doi:10.2196/65440. PMID 39509151. Three vials bought from illegal online pharmacies: semaglutide content 28.56%–38.69% above label; purity 7.7%–14.37% vs 99% claimed; no peptide-like impurities identified; no viable microbes; endotoxin detected in all samples (2.1645–8.9511 EU/mg). Very small sample (3 vials). Heavy metals: not reported in the abstract.
• ^R8 WADA: semaglutide is not named on the 2026 Prohibited List (checked against the official PDF). As an approved medicine it is not covered by S0 (non-approved substances). Unknown Not checked: WADA's 2026 Monitoring Program and the 2027 list.

Full reference list (all verified on PubMed, Oct 15, 2026)

• Wilding JPH, et al. N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183. PMID 33567185
• Marso SP, et al. N Engl J Med. 2016;375(19):1834-1844. doi:10.1056/NEJMoa1607141. PMID 27633186
• Lincoff AM, et al. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563. PMID 37952131
• Ashraf AR, et al. J Med Internet Res. 2024;26:e65440. doi:10.2196/65440. PMID 39509151
• Husain M, et al. N Engl J Med. 2019;381(9):841-851. doi:10.1056/NEJMoa1901118. PMID 31185157

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Disclaimer

This page is for education and harm reduction. It is not medical advice and not a recommendation to use semaglutide outside a prescription. Please talk to a clinician you trust, especially if you have a personal or family history of thyroid cancer or MEN 2, have had pancreatitis or gallbladder disease, have diabetic eye disease, take insulin, or are pregnant. Seek care right away for severe stomach pain or repeated vomiting, and report problems to FDA MedWatch (https://www.fda.gov/safety/medwatch).