Semaglutide: Trial Evidence, Risks and Compounded Versions

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Quick facts

Fact sheet

U.S. status

FDA-approvedCompounded versions: not FDA-approved

Strongest evidence

Human trials

Status verified

October 30, 2026

One of the best-studied drugs in the peptide world, and an FDA-approved one. Here is what the large trials found, where the evidence stops, and why a compounded version is a different product.

Key takeaways

• Semaglutide is FDA-approved. It is sold as Wegovy (weight and related conditions), Ozempic and Rybelsus (type 2 diabetes), each for the uses on its own label.
• The evidence is strong for weight, cardiovascular risk in people with heart disease, and kidney outcomes in type 2 diabetes. All of it comes from randomized trials.
• It has not been shown to help in early Alzheimer’s disease. Two phase 3 trials found no benefit.
• It carries a boxed warning for thyroid C-cell tumors, seen in rodents. Relevance to humans has not been determined.
• Compounded semaglutide is not FDA-approved. FDA does not review compounded drugs for safety, effectiveness or quality before they are sold.

Is semaglutide FDA-approved, and for what?

Yes. The same active ingredient is approved under several brand names, each with its own indications. Brand names are used here only to identify the approved products.

Dosing is set by each label and your prescriber. This guide does not give doses.

What did the major trials find?

Every trial below is a randomized, controlled trial in people. Results are averages; individual responses vary.

How strong is each result?

• Weight, heart events in people with established heart disease, and kidney outcomes in type 2 diabetes: strong. Large trials, hard outcomes or large effects, and an approved indication.
• MASH: moderate to high. The approval is accelerated and rests on liver biopsy findings; benefit on clinical outcomes is still to be confirmed.
• Knee osteoarthritis pain: moderate. One trial, and we did not find it listed as an indication on the Wegovy label.
• Alzheimer’s disease: negative.

Where SELECT does not apply

SELECT enrolled people who already had cardiovascular disease. Its result does not show that semaglutide lowers heart-attack risk in everyone who wants to lose weight.

How does it compare with tirzepatide?

In adults with obesity and no diabetes, SURMOUNT-5 (751 adults, 72 weeks, open-label, funded by Lilly, which makes tirzepatide) found weight loss of 13.7% with semaglutide vs 20.2% with tirzepatide. An earlier open-label trial in type 2 diabetes, SURPASS-2, also favored tirzepatide. See the full comparison.

What are the risks?

From the Wegovy label:

• Boxed warning: risk of thyroid C-cell tumors. It is contraindicated in people with a personal or family history of medullary thyroid carcinoma or with MEN 2. The tumors were seen in rodents; whether the risk applies to humans has not been determined.
• Warnings: acute pancreatitis, gallbladder disease, low blood sugar, acute kidney injury from dehydration, severe gastrointestinal reactions, hypersensitivity, worsening of diabetic retinopathy complications, increased heart rate, and lung aspiration during anesthesia or deep sedation.
• Stopping because of side effects: in SELECT, 16.6% of people on semaglutide stopped treatment because of adverse events, vs 8.2% on placebo.
• Suicidal behavior and ideation: this warning was removed from the label in February 2026.

What about the eye condition NAION?

NAION (nonarteritic anterior ischemic optic neuropathy) is a rare cause of sudden vision loss. Observational studies have linked semaglutide to it, but observational studies cannot prove cause.

• A single-center cohort found a hazard ratio of 4.28 in people with type 2 diabetes and 7.64 in people with overweight or obesity, with few events.
• A TriNetX analysis of people with diabetes found no significant difference through one year and hazard ratios of 2.05–2.44 at two to four years.
• A Danish study of people with type 2 diabetes found a hazard ratio of 2.19, with 0.228 vs 0.093 cases per 1,000 person-years.
• Europe’s drug-safety committee classified NAION as a very rare side effect (up to 1 in 10,000 people) in June 2025. We did not find the term in the Wegovy label version we reviewed.

Is compounded semaglutide the same as Wegovy or Ozempic?

No. FDA says compounded drugs are not reviewed for safety, effectiveness or quality before they are marketed, and that a compounded product should not be called “generic” or described as “the same as” an approved drug. The rules are shifting, so the details are dated here (checked Oct. 30, 2026):

• Semaglutide is not on the FDA drug shortage list or the 503B bulk substances list (FDA, April 1, 2026). In May 2026 FDA proposed not adding it to the 503B list. We found no final rule.
• Pharmacies’ broader latitude during the shortage ended April 24, 2025. Compounders remain limited in making products that are “essentially copies” of approved drugs.
• Adding vitamin B12 does not by itself settle the question. FDA says a version with a matching route and a concentration within 10% can still be an essential copy (FDA). A September 2026 FDA warning letter to a compounding pharmacy applied that reasoning. A warning letter is an agency position, not a court ruling.
• For salt forms of semaglutide (sodium, acetate), FDA says it is “not aware of any lawful basis” for their use (FDA, Oct. 1, 2026).
• FDA has received reports of adverse events, some requiring hospitalization, that may be related to dosing errors with compounded semaglutide; in some, patients took 5 to 20 times the intended dose. FDA also says it is aware of fraudulent compounded products, that it generally recommends using multi-dose vials within 28 days of first use, and that it has received complaints of products arriving warm.

We do not call compounded semaglutide “illegal” or “banned” across the board: it depends on conditions that differ by product and pharmacy. We do not recommend pharmacies or telehealth services.

What should you ask your doctor?

These questions come from the label’s warnings and contraindications, not from a protocol:

• Do I have a personal or family history of medullary thyroid carcinoma or MEN 2? (It rules semaglutide out.)
• Have I had pancreatitis or gallbladder disease, or do I have diabetic retinopathy?
• Do I take insulin or a drug that raises insulin, which can raise the risk of low blood sugar?
• Do I have a procedure coming up that involves anesthesia or deep sedation?
• Which product am I being prescribed: an FDA-approved one, or a compounded one? Who makes it?

Frequently asked questions

Is semaglutide the same as Ozempic?

Semaglutide is the active ingredient in Ozempic, Wegovy and Rybelsus. They are approved for different uses and come in different forms. Check each label.

Does semaglutide prevent dementia?

Not shown. Two phase 3 trials tested it in people who already had early Alzheimer’s disease and found no benefit at 104 weeks. They did not test prevention.

Does semaglutide cause blindness?

Observational studies have found an association with NAION, a rare eye condition. They cannot show that semaglutide caused it. Anyone with sudden vision changes should seek medical care promptly.

Does the SELECT heart result apply to everyone?

No. Participants already had cardiovascular disease.

Can compounded semaglutide replace the brand-name drug?

FDA says a compounded product is not the same as an approved one and has not been reviewed for safety, effectiveness or quality. Talk to a prescriber about your options.

Related guides

• Tirzepatide: Trial Evidence, Risks and Compounded Versions
• Semaglutide vs Tirzepatide: What Head-to-Head Data Show
• Best Peptides for Weight Loss: What the Evidence Shows
• Best Peptides for Joint Pain: What Human Evidence Exists
• Peptide Glossary: Plain-English Definitions

Sources we checked

1. Wegovy prescribing information (DailyMed, rev. 06/2026)FDA. Accessed October 30, 2026.
2. Ozempic prescribing information (DailyMed, rev. 01/2025)FDA. Accessed October 30, 2026.
3. Rybelsus prescribing information (DailyMed, rev. 1/2026)FDA. Accessed October 30, 2026.
4. Drugs@FDA record, NDA218316 (Wegovy tablets)FDA. Accessed October 30, 2026.
5. STEP 1 trial (PubMed)PubMed. Accessed October 30, 2026.
6. SELECT trial (PubMed)PubMed. Accessed October 30, 2026.
7. FLOW trial (PubMed)PubMed. Accessed October 30, 2026.
8. STEP 9 trial (PubMed)PubMed. Accessed October 30, 2026.
9. Phase 3 trial in MASH (PubMed)PubMed. Accessed October 30, 2026.
10. evoke and evoke+ Alzheimer's trials (PubMed)PubMed. Accessed October 30, 2026.
11. SURMOUNT-5 trial (PubMed)PubMed. Accessed October 30, 2026.
12. SURPASS-2 trial: tirzepatide vs semaglutide in type 2 diabetes (PubMed)PubMed. Accessed October 30, 2026.
13. NAION cohort study, single center (PubMed)PubMed. Accessed October 30, 2026.
14. NAION, TriNetX analysis (PubMed)PubMed. Accessed October 30, 2026.
15. NAION, Danish study (PubMed)PubMed. Accessed October 30, 2026.
16. EMA PRAC meeting highlights, June 2025Other. Accessed October 30, 2026.
17. FDA clarifies policies for compounders as national GLP-1 supply stabilizesFDA. Accessed October 30, 2026.
18. Federal Register: proposed 503B bulk drug substances list (May 1, 2026)Other. Accessed October 30, 2026.
19. FDA warning letter to a compounding pharmacy, Sept. 18, 2026FDA. Accessed October 30, 2026.
20. FDA's concerns with unapproved GLP-1 drugs used for weight lossFDA. Accessed October 30, 2026.
21. FDA: telehealth companies and promoting compounded drugsFDA. Accessed October 30, 2026.
22. FDA alert: dosing errors with compounded semaglutideFDA. Accessed October 30, 2026.

Written and maintained by the Best Peptides For Editorial Team. How we rate evidence.