What is semaglutide? What the research actually shows

Semaglutide is a GLP-1 receptor agonist, an approved prescription drug sold as Ozempic, Wegovy and Rybelsus.^[1][2][3] Large randomised trials show weight loss and fewer heart events. But the benefit is tied to staying on it, and nausea and vomiting are common.^[4][5][6][2]

What it is and what it is approved for

Semaglutide comes as a weekly injection and as daily tablets.^[1][2][3]

• The Ozempic injection label (June 2026) lists three uses in adults with type 2 diabetes: blood-sugar control, fewer major heart events in those with heart disease, and slower kidney decline in those with chronic kidney disease.^[1]
• The Wegovy label (June 2026) covers weight loss and long-term maintenance, alongside a reduced-calorie diet and more activity. It also covers fewer major heart events in adults with heart disease plus obesity or overweight.^[2]
• The Wegovy injection is also labelled for children 12 and older with obesity. It is labelled for the liver disease MASH with moderate-to-advanced fibrosis in adults, under accelerated approval that depends on a confirmatory trial.^[2]

What the trials show

In STEP 1, a double-blind trial of 1,961 adults with obesity or overweight and no diabetes, body weight fell 14.9% after 68 weeks on semaglutide 2.4 mg weekly. Placebo gave 2.4%.^[4] In that trial, 69.1% lost 10% or more of their weight, versus 12.0% on placebo.^[4]

In STEP 5, which followed 304 adults without diabetes, weight change at 104 weeks was -15.2% on semaglutide 2.4 mg. The loss held over two years while treatment continued.^[7]

In STEP 8, weekly semaglutide gave -15.8% body weight versus -6.4% for daily liraglutide over 68 weeks.^[8]

For heart risk, SELECT enrolled 17,604 adults with heart disease and overweight or obesity but no diabetes. Heart death, non-fatal heart attack or non-fatal stroke occurred in 6.5% on semaglutide 2.4 mg versus 8.0% on placebo (hazard ratio 0.80).^[5] SUSTAIN 6 studied 3,297 adults with type 2 diabetes at high heart risk. The main heart outcome occurred in 6.6% versus 8.9% on placebo (hazard ratio 0.74).^[9]

What happens when people stop

Stopping matters. In the STEP 1 extension (327 people), those who stopped semaglutide and lifestyle support regained 11.6 percentage points of body weight within a year, about two-thirds of what they had lost.^[6] In STEP 4 (803 people), switching to placebo after a 20-week run-in gave +6.9% weight change, versus -7.9% for those who continued.^[10]

Our sources say the evidence on very long use is limited.^[6][7]

Doses as studied

This is what the labels and trials report, not advice.

• The Wegovy injection label starts at 0.25 mg for 4 weeks, then steps up every 4 weeks (0.5, 1, 1.7 mg) to the usual maintenance dose of 2.4 mg once weekly.^[2]
• STEP 1, STEP 4, STEP 5 and STEP 8 used 2.4 mg once weekly under the skin in adults with overweight or obesity and no diabetes.^{[4][10][7][8]}
• SUSTAIN 6 used 0.5 or 1 mg once weekly for 104 weeks in adults with type 2 diabetes.^[9]

Side effects and warnings

Both labels carry a boxed warning for thyroid C-cell tumours, including medullary thyroid cancer.^[2][1] In rodents, semaglutide caused these tumours at exposures similar to those used in people. Whether it does this in humans has not been determined.^[1][2]

The Wegovy label's adult injection trials reported:

• Nausea in 44% versus 16% on placebo.^[2]
• Vomiting in 24% versus 6%.^[2]
• Diarrhoea in 30% versus 16%, and constipation in 24% versus 11%.^[2]
• Stopping because of side effects in 6.8% versus 3.2% on placebo.^[2]

In SELECT, stopping the drug because of side effects was twice as common: 16.6% versus 8.2%.^[5] In SUSTAIN 6, eye complications of diabetic retinopathy were more common on semaglutide (hazard ratio 1.76).^[9]

Other label warnings include acute pancreatitis, gallbladder disease, acute kidney injury and serious allergic reactions. They also include low blood sugar with insulin or sulfonylureas.^[2][1] The labels say it is contraindicated with a personal or family history of medullary thyroid cancer or MEN 2.^[2][1]

Compounded and 'research' vials

On 2025-02-21 FDA declared the semaglutide injection shortage resolved.^[11] FDA says compounded GLP-1 drugs are not reviewed for safety, effectiveness or quality.^[12]

FDA has received reports of overdoses, some needing hospital care, from dosing errors with compounded vials. Patients drew up the wrong dose or mixed up mL, mg and 'units'. Semaglutide's half-life is about one week.^[13]

'Research use only' semaglutide sold online is a different matter. FDA warning letters, including one dated 2026-08-24 to Peptide Partners LLC, treat such products as unapproved new drugs.^[14][15]

The big trials tested the branded products in screened trial populations. No cited trial tested compounded or 'research' semaglutide, so its benefit and safety are unmeasured.^[4][5][12]

The bottom line

Trials show clear weight loss and fewer heart events in the groups studied.^[4][5] The trade-offs are real: frequent stomach side effects, a boxed warning, and weight that drifts back after stopping.^[2][6] The evidence applies to the approved, branded products. Our sources don't show that compounded or 'research' vials deliver the same results.^[12]