Peptide Graded

All peptides / Gut and weight

Semaglutide

GLP-1 receptor agonist

Also Ozempic, Wegovy, Rybelsus, Sema, Compounded semaglutide, NN9535

Evidence
AStrong human evidence
FDA status
FDA approvedas of 2026-10-26
Route
Several routes
Studies cited
11 human0 animal or cell

It is the shot behind Ozempic and Wegovy, used for diabetes and weight loss. Trials in tens of thousands of people show about 15% weight loss and fewer heart attacks.

Sold for

Semaglutide is the GLP-1 injection behind Ozempic and Wegovy, the most talked-about weight loss drug of the decade.

Studies say

Randomized trials in tens of thousands of people show about 15 percent weight loss, roughly a 1 to 2 point HbA1c reduction, a 20 percent cut in major cardiovascular events and slower kidney decline, with gastrointestinal side effects and weight regain after stopping as the main caveats.

Why grade A. Semaglutide has one of the largest trial programs of any peptide: the STEP trials in obesity (STEP 1, 1,961 adults), the SUSTAIN trials in type 2 diabetes, SELECT (17,604 adults with cardiovascular disease and obesity, the largest), FLOW in kidney disease, and systematic reviews pooling tens of thousands of participants. Weight loss, glucose lowering and reductions in heart attack, stroke and kidney outcomes are all shown in randomized placebo-controlled trials. What remains open is what happens over decades and how to stop without regaining. 2356910

FDA. Semaglutide is FDA-approved as Ozempic (weekly injection, type 2 diabetes, 2017; with later indications to reduce cardiovascular events and, since January 2025, kidney disease progression in type 2 diabetes), Rybelsus (daily tablet, type 2 diabetes, 2019), and Wegovy (weekly injection, chronic weight management, 2021; cardiovascular risk reduction in obesity, 2024; MASH with liver fibrosis, 2025; an oral Wegovy tablet, December 2025). Compounded semaglutide is not FDA-approved. 17131415

Written from 17 cited sources. Last refreshed 2026-10-27. Not physician reviewed.

What this means for you

What people take it for
Type 2 diabetes and losing weight
Can a US doctor prescribe it?
Yes, FDA approved for type 2 diabetes, weight loss, heart protection and kidney disease in diabetes.
Properly tested in people?
Yes, in large controlled trials. One trial followed 17,604 people.

Evidence checklist

  • Randomised controlled trial STEP, SUSTAIN, SELECT, FLOW trialsyes
  • Human study over 100 people SELECT, 17,604 adults; STEP 1, 1,961yes
  • More than one research group Many trial programmes plus pooled reviewsyes
  • Clinical outcomes, not surrogate markers Heart attack, stroke, kidney outcomes reducedyes
  • Human safety data beyond case reports Large trials; GI effects, boxed thyroid warningyes

Drawn from the cited studies below. A dash means the sources give no information.

What it is

Semaglutide is a modified version of GLP-1, a gut hormone of 30 amino acids. The gut releases it after meals. Two amino acid changes protect semaglutide from the enzyme that destroys native GLP-1 within minutes. A fatty acid chain lets it bind albumin in the blood. This stretches its half-life to about a week. Novo Nordisk developed it as a successor to daily liraglutide. The oral forms pair the peptide with an absorption enhancer. This lets enough survive the stomach to work. 17

The same molecule is sold at different doses under three brands. Ozempic and Rybelsus are for type 2 diabetes. Wegovy is the higher-dose version for weight management. It is now also approved to lower cardiovascular risk and to treat liver disease. Demand has outrun supply at times. That fed a market in compounded semaglutide, and the FDA has warned about it repeatedly. 1715

How it works

Semaglutide activates GLP-1 receptors in several places at once. In the pancreas it raises insulin release when glucose is high. It also suppresses glucagon. This lowers blood sugar without causing low blood sugar on its own. In the stomach it slows emptying, so meals feel filling for longer. In the brain it acts on appetite centers in the hypothalamus and brainstem. This reduces hunger and food cravings. That is where most of the weight loss comes from. Weight loss explains only part of the heart benefit. In SELECT, an estimated third of the drop in heart attacks and strokes was mediated through a smaller waist. The benefit was present regardless of starting weight. This suggests direct effects on blood vessels and inflammation. 1711

What human research shows

STEP 1 randomized 1,961 adults with obesity but no diabetes. They got weekly semaglutide or placebo for 68 weeks, alongside lifestyle counseling. Mean weight loss was 14.9 percent versus 2.4 percent. Half of semaglutide patients lost at least 15 percent. STEP 8 was a head-to-head trial in 338 adults. Semaglutide produced 15.8 percent weight loss versus 6.4 percent with daily liraglutide. STEP 4 showed what happens to people who stop. All took the drug for 20 weeks. Those then switched to placebo regained 6.9 percent over the next 48 weeks. Those who continued lost a further 7.9 percent. In the STEP 1 extension, participants who stopped treatment regained two-thirds of their lost weight within a year. 26812

SELECT enrolled 17,604 adults aged 45 and older. All had cardiovascular disease and overweight or obesity, but no diabetes. Over a mean of 40 months, cardiovascular death, heart attack or stroke occurred in 6.5 percent on semaglutide. On placebo it was 8.0 percent. That is a 20 percent relative reduction. The benefit held in the quarter of participants with heart failure. It held across all baseline weights. FLOW enrolled people with type 2 diabetes and chronic kidney disease. It showed a 24 percent reduction in kidney disease progression and cardiovascular death. 39101113

In type 2 diabetes, SUSTAIN FORTE compared two semaglutide doses in 961 adults. HbA1c fell by 1.9 to 2.2 percentage points over 40 weeks. A 2023 meta-analysis of 17 trials in 14,940 patients found HbA1c drops of about 1 to 1.4 points versus placebo. A network meta-analysis of 28 trials compared it with tirzepatide. Tirzepatide lowered HbA1c and weight more. The SURMOUNT-1 tirzepatide trial reported up to 20.9 percent weight loss, above semaglutide's 15 percent. But the two have been compared directly only in diabetes. 451617

StudyModelFinding
STEP 1Humans, n=1,961 with obesity, randomized, double-blind, placebo-controlled, 68 weeks14.9 percent mean weight loss versus 2.4 percent on placebo. 2
SELECTHumans, n=17,604 with cardiovascular disease and overweight or obesity, randomized, placebo-controlled, mean 40 months20 percent relative reduction in cardiovascular death, heart attack or stroke. 3
FLOWHumans, adults with type 2 diabetes and chronic kidney disease, randomized, placebo-controlled24 percent reduction in kidney disease progression and cardiovascular death. 13
STEP 4 withdrawal trialHumans, n=803 after 20-week run-in, randomized to continue or switch to placebo, 48 weeksContinued semaglutide lost a further 7.9 percent; those switched to placebo regained 6.9 percent. 8
STEP 8Humans, n=338, randomized, open-label semaglutide versus liraglutide, 68 weeks15.8 percent weight loss with semaglutide versus 6.4 percent with liraglutide. 6

Safety

Nausea, diarrhea, vomiting and constipation are the common side effects. They hit a large share of users early in treatment and fade for most. In STEP 1, 4.5 percent stopped because of them. In SELECT, 16.6 percent stopped for adverse events versus 8.2 percent on placebo. Gallbladder disease is more frequent. Rapid weight loss itself causes gallstones, in part. The label carries a boxed warning about thyroid C-cell tumors seen in rodents. No human signal has been confirmed. The label bars use in people with a personal or family history of medullary thyroid cancer. Pancreatitis is listed as a risk. But the meta-analysis in diabetes did not find an excess. Slow stomach emptying has been linked to aspiration during anesthesia. One diabetes trial saw a small rise in diabetic retinopathy complications. The trials have also documented two practical concerns. Users lose lean mass alongside fat. And nearly everyone regains weight after stopping. 1235712

Questions for your clinician

  • What happens to my weight if I stop?
  • Do I have a history that makes the thyroid warning relevant?
  • How long is treatment expected to continue?

Questions people ask

How does semaglutide reduce appetite and weight?

It activates GLP-1 receptors in the brain's appetite centers. This lowers hunger and cravings. It also slows stomach emptying, so meals satisfy for longer. Most of the weight loss comes from eating less. The drug does not raise energy use. 17

What were the SELECT trial's results?

17,604 people had heart disease and excess weight but no diabetes. Semaglutide cut the combined rate of cardiovascular death, heart attack and stroke by 20 percent over about three years. The benefit was similar across starting weights. Weight lost explained only part of it. This led to the 2024 approval of Wegovy for lowering cardiovascular risk. 311

Does the weight return after stopping semaglutide?

It comes back. In STEP 4, people switched to placebo regained about 7 percent of body weight within a year. Those who continued kept losing. In the STEP 1 extension, two-thirds of lost weight returned within a year of stopping. Blood pressure and lipids drifted back too. 812

Is compounded semaglutide the same thing?

Not in regulatory terms. Compounded versions are not FDA-approved. The agency does not verify what is in them. Some have used salt forms of semaglutide that have never been tested in humans. The FDA allowed compounding during shortages and has since restricted it. 15

How does semaglutide compare with tirzepatide?

Tirzepatide activates GIP receptors as well as GLP-1 receptors. In its own trial it produced up to 20.9 percent weight loss. Semaglutide's figure was roughly 15 percent. A network meta-analysis of 28 diabetes trials found tirzepatide lowered HbA1c and weight more at every dose. Both have the same stomach and gut side effects. 1617

Citations

  1. Ozempic (semaglutide) prescribing information, FDA, 2023 accessdata.fda.gov
  2. Wilding 2021, N Engl J Med: once-weekly semaglutide in adults with overweight or obesity (STEP 1) pubmed.ncbi.nlm.nih.gov
  3. Lincoff 2023, N Engl J Med: semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT) pubmed.ncbi.nlm.nih.gov
  4. Frías 2021, Lancet Diabetes Endocrinol: higher versus standard dose semaglutide in type 2 diabetes (SUSTAIN FORTE) pubmed.ncbi.nlm.nih.gov
  5. Diabetol Metab Syndr 2023: systematic review and meta-analysis of subcutaneous semaglutide in type 2 diabetes pubmed.ncbi.nlm.nih.gov
  6. Rubino 2022, JAMA: semaglutide versus liraglutide for weight loss (STEP 8) pubmed.ncbi.nlm.nih.gov
  7. Wegovy (semaglutide) prescribing information, DailyMed dailymed.nlm.nih.gov
  8. Rubino 2021, JAMA: continued semaglutide versus placebo for weight maintenance (STEP 4) pubmed.ncbi.nlm.nih.gov
  9. Deanfield 2024, Lancet: semaglutide in patients with obesity and heart failure, SELECT prespecified analysis pubmed.ncbi.nlm.nih.gov
  10. Lincoff 2023, N Engl J Med: SELECT trial (DOI record) doi.org
  11. Lancet 2025: semaglutide and cardiovascular outcomes by adiposity measures, SELECT prespecified analysis pubmed.ncbi.nlm.nih.gov
  12. Wilding 2022, Diabetes Obes Metab: weight regain after withdrawal of semaglutide, STEP 1 extension pubmed.ncbi.nlm.nih.gov
  13. Perkovic 2024, N Engl J Med: effects of semaglutide on chronic kidney disease in type 2 diabetes (FLOW) doi.org
  14. AJMC 2025: FDA approves semaglutide for MASH with fibrosis ajmc.com
  15. Healio 2026: FDA approves Wegovy pill, the first oral GLP-1 for obesity healio.com
  16. Jastreboff 2022, N Engl J Med: tirzepatide once weekly for obesity (SURMOUNT-1) pubmed.ncbi.nlm.nih.gov
  17. Karagiannis 2024, Diabetologia: tirzepatide versus semaglutide in type 2 diabetes, network meta-analysis pubmed.ncbi.nlm.nih.gov

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