Semaglutide is a long-acting copy of glucagon-like peptide-1 (GLP-1), a gut hormone that boosts insulin release after meals and reduces appetite. Novo Nordisk sells it as Ozempic (a weekly injection for type 2 diabetes), Rybelsus (a daily tablet for type 2 diabetes) and Wegovy (a weekly injection, and now also a daily tablet, for weight management).
Its key fact is that it is a fully approved drug backed by large outcome trials. At 2.4 mg/week it produced about 15% average weight loss over 68 weeks in adults with obesity, and it lowered major cardiovascular events by 20% in people with heart disease and overweight. Most of the lost weight returns after the drug is stopped, and roughly 25–35% of the weight lost is lean mass.
This page summarizes what the FDA labels, the clinical trials and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | GLP-1 receptor agonist (modified GLP-1 peptide) |
| Brands / first US approval | Ozempic injection (December 2017); Rybelsus tablets (September 2019); Wegovy injection (June 2021); Wegovy tablets (later added to the Wegovy label) |
| Route | Subcutaneous injection once weekly, or oral tablet once daily |
| Labeled maintenance doses | Ozempic 0.5–2 mg/week; Wegovy 1.7 or 2.4 mg/week (up to 7.2 mg/week for weight); Wegovy tablet 25 mg/day; Rybelsus 7 or 14 mg/day |
| Half-life (label) | About 1 week; still in the circulation for about 5–7 weeks after the last dose |
| Bioavailability (label) | 89% by injection; about 0.4–2% as a tablet |
| Boxed warning | Thyroid C-cell tumors in rodents; contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2 |
| US status | Prescription-only drug; FDA declared the semaglutide injection shortage resolved on February 21, 2025 |
What it is
Semaglutide is a peptide with 94% sequence homology to human GLP-1. Its formula is C₁₈₇H₂₉₁N₄₅O₅₉ and its molecular weight is 4113.58 g/mol. The peptide backbone is made by yeast fermentation (Ozempic label; PubChem).
Novo Nordisk designed semaglutide for once-weekly dosing by changing three things (Lau et al., J Med Chem 2015):
| Change | What it does |
|---|---|
| Aminoisobutyric acid (Aib) at position 8 | Protects against the enzyme DPP-4, which normally inactivates GLP-1 |
| Fatty di-acid (C18) chain with a spacer attached to lysine 26 | Binds the drug tightly to albumin, the main blood protein, which slows kidney clearance and breakdown |
| Arginine at position 34 | Ensures only one fatty chain attaches |
In the discovery paper, semaglutide bound the GLP-1 receptor about three times less tightly than liraglutide, but bound albumin more strongly. This trade-off produced a much longer half-life. That paper reported a 46-hour plasma half-life after IV dosing in mini-pigs. The human half-life is longer (see below).
Semaglutide activates the GLP-1 receptor. According to the labels, this:
- raises insulin and lowers glucagon, both only when blood glucose is high;
- slows early stomach emptying after meals;
- reduces appetite and calorie intake through GLP-1 receptors in brain areas that regulate eating.
The labels state that the drug lowers body weight “with greater fat mass loss than lean mass loss.” They also say the mechanisms behind the heart and kidney benefits have not been established.
Pharmacokinetics
From the Ozempic, Wegovy and oral semaglutide labels (Ozempic label; Wegovy label; Rybelsus / oral Ozempic label):
| Parameter | Injection | Tablet |
|---|---|---|
| Absolute bioavailability | 89% | About 0.4–1% (Rybelsus); about 1–2% (newer tablets) |
| Time to peak | 1–3 days | About 1 hour |
| Albumin binding | Over 99% | Over 99% |
| Elimination half-life | About 1 week | About 1 week |
| Steady state | After 4–5 weeks of weekly dosing | After 4–5 weeks of daily dosing |
| Urine excretion as intact drug | About 3% | — |
The body clears semaglutide by cutting up the peptide and breaking down the fatty chain. The labels report very low potential to inhibit or induce CYP liver enzymes, and kidney or liver impairment did not change its kinetics in a clinically relevant way.
Tablets contain an absorption enhancer called SNAC and are absorbed mainly in the stomach. This is why the label requires taking them on an empty stomach with no more than 4 ounces of water and waiting at least 30 minutes before eating or taking other drugs. Tablet levels are also more variable than injected levels. With Wegovy 25 mg tablets, 90% of patients had average concentrations between 27 and 186 nmol/L, compared with 51–110 nmol/L for the 2.4 mg injection.
Exposure rises in proportion to dose. Average steady-state levels were about 75 nmol/L on Wegovy 2.4 mg/week and about 230 nmol/L on 7.2 mg/week.
Approved medical use
| Product | Form | US-approved uses |
|---|---|---|
| Ozempic | Weekly injection, 0.25–2 mg | Blood sugar control in adults with type 2 diabetes; lowering major cardiovascular events in type 2 diabetes with heart disease; lowering kidney failure, sustained eGFR decline and cardiovascular death in type 2 diabetes with chronic kidney disease |
| Rybelsus and Ozempic tablets | Daily tablet | Blood sugar control in adults with type 2 diabetes; lowering major cardiovascular events in high-risk type 2 diabetes |
| Wegovy injection | Weekly injection, up to 2.4 mg (7.2 mg as Wegovy HD for weight) | Weight reduction and maintenance in adults and children 12 and older with obesity, and in adults with overweight plus a weight-related condition; lowering major cardiovascular events in adults with heart disease and overweight or obesity; noncirrhotic MASH with moderate to advanced fibrosis (accelerated approval) |
| Wegovy tablets | Daily tablet, 25 mg maintenance | Weight reduction and maintenance in adults; lowering major cardiovascular events in adults with heart disease and overweight or obesity |
Every product starts low and steps up to reduce nausea and other stomach side effects:
- Wegovy injection starts at 0.25 mg/week and increases every 4 weeks (0.5, 1 and 1.7 mg) to 2.4 mg/week by week 17. For weight reduction, adults who tolerate 2.4 mg for at least 4 weeks may go up to a maximum of 7.2 mg/week.
- Ozempic starts at 0.25 mg/week, then 0.5 mg. The dose can rise to 1 mg and then 2 mg, at least 4 weeks apart, if blood sugar needs more control.
- Wegovy tablets start at 1.5 mg/day and go up every 30 days (4 and 9 mg) to 25 mg/day.
The labels say not to combine semaglutide with other semaglutide products or other GLP-1 receptor agonists (Wegovy label; Drugs@FDA).
What the research shows
Weight loss
All the main weight-loss trials paired semaglutide or placebo with diet and activity counseling, and enrolled adults with a BMI of 27 or higher (30 or higher in STEP UP):
| Trial | n | Duration | Dose | Weight change on semaglutide | Weight change on placebo |
|---|---|---|---|---|---|
| STEP 1 (Wilding et al., NEJM 2021) | 1,961 | 68 weeks | 2.4 mg/week injection | −14.9% (−15.3 kg) | −2.4% (−2.6 kg) |
| STEP UP (Wharton et al., Lancet Diabetes Endocrinol 2025) | 1,407 | 72 weeks | 7.2 mg/week injection (2.4 mg arm for comparison) | −18.7% (2.4 mg: −15.6%) | −3.9% |
| OASIS 4 (Wharton et al., NEJM 2025) | 307 | 64 weeks | 25 mg/day tablet | −13.6% | −2.2% |
In STEP 1, half of the participants on semaglutide (50.5%) lost at least 15% of their body weight, compared with 4.9% on placebo. In STEP UP, 7.2 mg beat 2.4 mg by 3.1 percentage points (95% CI 1.6–4.7). The higher dose also caused more stomach side effects (70.8% vs 61.2%) and more skin sensations (see side effects).
What happens after stopping
Two trials tested what happens when semaglutide is withdrawn:
- STEP 4. After 20 weeks on semaglutide (average loss 10.6%), 803 adults were randomized to continue or switch to placebo for 48 weeks. Those who continued lost a further 7.9%, while those switched to placebo regained 6.9% (Rubino et al., JAMA 2021).
- STEP 1 extension. 327 participants stopped all treatment at week 68 and were followed for one more year. The semaglutide group had lost 17.3% by week 68 and regained 11.6 percentage points by week 120, a net loss of 5.6%. Most improvements in blood pressure, lipids and blood sugar markers also moved back toward baseline (Wilding et al., Diabetes Obes Metab 2022).
In other words, about two-thirds of the weight lost came back within a year of stopping. The authors concluded that ongoing treatment is needed to maintain the benefit.
Lean mass and muscle
Any large weight loss includes some lean mass (muscle, organs, water and other non-fat tissue). Two 2026 reviews of randomized trials looked at how much:
- A meta-analysis of 20 trials with 15,782 participants estimated that lean mass made up 35.2% (95% CI 31.5–38.9) of weight lost on semaglutide. The comparable figure was 26.2% for lifestyle interventions alone, and the difference between drug and lifestyle groups was not statistically significant. Diet plus resistance training gave the best result, 17.5% (Eisa and Barood, Diabetes Obes Metab 2026).
- A systematic review of 35 trials across incretin drugs (semaglutide, tirzepatide, liraglutide, dulaglutide) found a median of 28.3% of weight lost came from muscle-related measures, with wide variation. None of the trials measured objective physical function (Batsis et al., Ann Intern Med 2026).
These data come from people with overweight or obesity. We found no controlled trials of semaglutide in lean or resistance-trained people, so claims about “cutting” without muscle loss in that population are untested.
Cardiovascular outcomes
| Trial | Population | Dose | Major cardiovascular events (semaglutide vs placebo) | Hazard ratio (95% CI) |
|---|---|---|---|---|
| SUSTAIN-6 (Marso et al., NEJM 2016) | 3,297 people with type 2 diabetes at high risk, 104 weeks | 0.5 or 1 mg/week | 6.6% vs 8.9% | 0.74 (0.58–0.95) |
| SELECT (Lincoff et al., NEJM 2023) | 17,604 people with heart disease and BMI 27 or higher, no diabetes; mean follow-up 39.8 months | 2.4 mg/week | 6.5% vs 8.0% | 0.80 (0.72–0.90) |
| SOUL (McGuire et al., NEJM 2025) | 9,650 people with type 2 diabetes and heart or kidney disease; median follow-up 49.5 months | Up to 14 mg/day tablet | 12.0% vs 13.8% | 0.86 (0.77–0.96) |
“Major cardiovascular events” here means cardiovascular death, nonfatal heart attack or nonfatal stroke. In SELECT, 16.6% of semaglutide patients stopped the drug because of adverse events, compared with 8.2% on placebo.
Kidney disease in type 2 diabetes
The FLOW trial randomized 3,533 people with type 2 diabetes and chronic kidney disease to 1 mg/week or placebo. It was stopped early for benefit after a median 3.4 years (Perkovic et al., NEJM 2024). Results:
- Major kidney events (kidney failure, a 50% or greater drop in kidney function, or kidney or cardiovascular death): 24% lower, HR 0.76 (95% CI 0.66–0.88).
- Cardiovascular death: HR 0.71 (95% CI 0.56–0.89).
- Death from any cause: HR 0.80 (95% CI 0.67–0.95).
- Kidney function: declined 1.16 mL/min/1.73 m² per year more slowly.
Blood sugar in type 2 diabetes
In the 30-week monotherapy trial on the Ozempic label (388 patients), HbA1c (a measure of average blood sugar over about 3 months) fell from a baseline of about 8% (Ozempic label):
| Arm | HbA1c change | Reached HbA1c under 7% | Weight change |
|---|---|---|---|
| Placebo | −0.1% | 28% | −1.2 kg |
| 0.5 mg/week | −1.4% | 73% | −3.8 kg |
| 1 mg/week | −1.6% | 70% | −4.7 kg |
Fatty liver disease (MASH)
ESSENCE randomized 1,197 adults with biopsy-proven MASH (metabolic dysfunction-associated steatohepatitis, an inflammatory form of fatty liver disease) and moderate to advanced fibrosis to 2.4 mg/week or placebo. In the planned 72-week analysis of the first 800 patients (Sanyal et al., NEJM 2025):
- Steatohepatitis resolved without worsening fibrosis in 62.9% vs 34.3%.
- Fibrosis improved without worsening steatohepatitis in 36.8% vs 22.4%.
- Body weight fell 10.5% vs 2.0%.
FDA approved this use under accelerated approval. Continued approval depends on confirmatory outcome data.
Side effects and risks
Boxed warning: thyroid C-cell tumors
In lifetime studies in mice and rats, semaglutide caused dose- and duration-dependent thyroid C-cell tumors (adenomas and carcinomas) at clinically relevant exposures. Whether this applies to humans is unknown. The labels say:
- semaglutide is contraindicated in people with a personal or family history of medullary thyroid carcinoma (MTC), or with multiple endocrine neoplasia type 2 (MEN 2);
- routine calcitonin testing or thyroid ultrasound is of uncertain value for early detection.
Gastrointestinal effects
Stomach and bowel effects are the most common reason people stop. In the three 2.4 mg weight-management trials (2,116 on semaglutide, 1,261 on placebo) (Wegovy label):
| Adverse reaction | Placebo | Semaglutide 2.4 mg |
|---|---|---|
| Nausea | 16% | 44% |
| Diarrhea | 16% | 30% |
| Vomiting | 6% | 24% |
| Constipation | 11% | 24% |
| Abdominal pain | 10% | 20% |
| Headache | 10% | 14% |
| Fatigue | 5% | 11% |
| Hair loss | 1% | 3% |
| Stopped because of side effects | 3.2% | 6.8% |
Severe gastrointestinal reactions occurred in 4.1% of patients on Wegovy injection vs 0.9% on placebo. Postmarketing reports include ileus (stalled bowel), intestinal obstruction and fecal impaction. Semaglutide is not recommended for people with severe gastroparesis.
Vomiting and diarrhea can cause dehydration. There are postmarketing reports of acute kidney injury from this, some requiring dialysis.
At 7.2 mg/week, dysesthesia (abnormal skin sensations such as tingling, burning or skin sensitivity) was reported by 22.9% of participants, compared with 6.0% on 2.4 mg and 0.5% on placebo (Wharton et al., STEP UP).
Pancreas and gallbladder
In adult weight-management trials, the Wegovy label reports:
- acute pancreatitis, confirmed in 4 semaglutide-treated patients (0.2 cases per 100 patient-years) vs 1 on placebo; fatal cases have been reported with the GLP-1 class;
- gallstones, in 1.6% on injection vs 0.7% on placebo, and 2.5% on tablets vs 1% on placebo;
- gallbladder inflammation (cholecystitis), in 0.6% vs 0.2%.
Rates were higher in adolescents. The label notes that the gallbladder excess remained after accounting for the amount of weight lost.
Heart rate
Resting heart rate rose by an average of 1–4 beats per minute vs placebo. A peak increase of 20 bpm or more at any visit occurred in 26% on semaglutide vs 16% on placebo. The label advises stopping the drug if the resting heart rate stays elevated.
Eyes
- Diabetic retinopathy. In SUSTAIN-6, retinopathy complications were more common on semaglutide (3.0% vs 1.8%; HR 1.76, 95% CI 1.11–2.78). The excess was concentrated in people who already had retinopathy. Rapid blood sugar improvement is known to temporarily worsen retinopathy.
- NAION. In June 2025 the EMA’s safety committee concluded that non-arteritic anterior ischemic optic neuropathy (a sudden loss of blood flow to the optic nerve that can cause vision loss) is a “very rare” side effect of semaglutide, affecting up to 1 in 10,000 people. It recommended stopping treatment if NAION is confirmed (EMA PRAC, June 2025). The current US labels do not list it.
Other label warnings
- Hypoglycemia (low blood sugar), mainly when combined with insulin or sulfonylureas, which may need dose reductions.
- Serious allergic reactions, including anaphylaxis and angioedema.
- Pulmonary aspiration during general anesthesia or deep sedation, because food can remain in the stomach. Patients should tell their care team before procedures.
- Pen sharing can spread blood-borne infections, even with a new needle.
Mood and suicidal thoughts
Wegovy originally carried a warning about suicidal behavior and ideation, inherited from older weight-loss drugs. In January 2026, after a comprehensive review, FDA found no increased risk of suicidal thoughts or behavior with GLP-1 receptor agonists and asked manufacturers to remove the warning (FDA Drug Safety Communication, 2026). The current Wegovy label lists it as removed.
Interactions
- Oral medicines. Slower stomach emptying can change how other oral drugs are absorbed. With semaglutide tablets, levothyroxine exposure rose by 33%. The label advises closer monitoring of narrow-therapeutic-index drugs.
- Insulin and sulfonylureas. These raise the risk of hypoglycemia.
- Other GLP-1 drugs. These include tirzepatide and liraglutide, and combining them with semaglutide is not recommended.
Who should not use it
- People with a personal or family history of MTC, or with MEN 2.
- People who have had a serious hypersensitivity reaction to semaglutide.
- Pregnancy: the label says it may cause fetal harm based on animal studies. For weight management, it should be stopped when pregnancy is recognized, and at least 2 months before a planned pregnancy because of the long washout.
Compounded, counterfeit and “research” semaglutide
Semaglutide injection was on FDA’s drug shortage list from 2022 until February 21, 2025, when FDA declared the shortage resolved. While a drug is on the shortage list, federal law gives compounders more room to make copies. FDA now states that semaglutide is on neither the shortage list nor the outsourcing-facility bulks list, and that pharmacies may not regularly compound what are essentially copies of the approved drug (FDA compounding statement).
FDA lists several problems with unapproved semaglutide (FDA, unapproved GLP-1 drugs):
- Dosing errors. Some hospitalizations involved patients measuring doses from multi-dose vials, and doses above or faster than the approved label.
- Salt forms. Semaglutide sodium and semaglutide acetate are different active ingredients from the approved drug, and FDA knows of no lawful basis for compounding with them.
- Counterfeits and fraud. These include counterfeit Ozempic and fake pharmacy labels.
- “For research purposes” products. FDA has warned companies selling semaglutide labeled “not for human consumption” directly to consumers with dosing instructions.
- Adverse event reports. As of May 31, 2026, FDA had received 990 adverse event reports linked to compounded semaglutide. It notes these are likely underreported.
Key takeaways
- A modified GLP-1 built to last a week. Changes at positions 8, 26 and 34 resist breakdown and bind albumin, giving a half-life of about one week by injection or tablet.
- Large, well-documented weight loss. Average loss was about 15% at 2.4 mg/week over 68 weeks and about 19% at 7.2 mg/week over 72 weeks in adults with obesity, compared with 2–4% on placebo.
- Benefits beyond weight. It lowered major cardiovascular events by 20% in SELECT and kidney outcomes by 24% in FLOW, and it is approved for fatty liver disease with fibrosis.
- Weight returns after stopping. About two-thirds of lost weight came back within a year off the drug.
- Lean mass is part of the loss. Lean mass made up roughly 25–35% of weight lost, which one meta-analysis found similar to diet alone. Resistance training reduced that share, and there are no trials in lean athletes.
- Stomach side effects dominate. Nausea affected 44% at 2.4 mg. Gallbladder disease, pancreatitis, heart-rate increases and a rodent thyroid-tumor boxed warning are the main label risks.
Sources
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- Novo Nordisk. Wegovy (semaglutide) injection and tablets, prescribing information. DailyMed; Drugs@FDA, NDA 215256.
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