What semaglutide is
Semaglutide is a GLP-1 receptor agonist. It is sold as Wegovy for weight management, as Ozempic for type 2 diabetes, and as Rybelsus in tablet form, also for type 2 diabetes. Same molecule, different doses, different approved uses.
It is the most studied compound in this category by a wide margin. Large randomised trials, a cardiovascular outcomes trial with hard endpoints, and years of post-marketing use. Whatever its drawbacks, an absence of evidence is not one of them.
How treatment works in practice
It is a once-weekly subcutaneous injection, taken on the same day each week, with or without food. You inject into the abdomen, thigh or upper arm, rotating the site.
Treatment starts at 0.25 mg and climbs in steps no sooner than four weeks apart to a maintenance dose of 2.4 mg. The climb exists to let your gut adapt, and moving faster is the most common avoidable cause of a miserable first couple of months.
The oral formulation follows an entirely different schedule. It is taken daily on an empty stomach with no more than 120 ml of plain water, and you wait at least 30 minutes before eating, drinking or taking anything else. Absorption is poor and fragile, which is what those instructions are protecting.
Who is eligible
The approved criteria in the United States are a BMI of 30 or above, or 27 or above with at least one weight-related condition, alongside a reduced-calorie diet and increased physical activity. Wegovy also carries an indication for adolescents aged 12 and over with a BMI at or above the 95th percentile for age and sex.
It is contraindicated if you or a family member has had medullary thyroid carcinoma, or if you have multiple endocrine neoplasia syndrome type 2. It is not for use in pregnancy, and the labelled advice is to stop at least two months before a planned pregnancy given how long it stays in the body.
A history of pancreatitis, gallbladder disease, severe gastrointestinal disease including gastroparesis, or diabetic retinopathy does not automatically rule it out, but each one changes the conversation and needs raising explicitly.
What the results look like
STEP 1 randomised 1,961 adults with overweight or obesity and without diabetes. Over 68 weeks, mean body weight fell about 15% on semaglutide 2.4 mg against roughly 2.4% on placebo, both alongside lifestyle counselling. Around a third of participants lost 20% or more.
STEP 5 followed people for 104 weeks and found the loss was broadly sustained at about 15%, which is the longest randomised evidence available.
In STEP 2, in adults with type 2 diabetes, mean loss was closer to 10%. That gap is consistent across this whole class and is worth knowing in advance rather than experiencing as a disappointment.
In STEP 8, semaglutide 2.4 mg produced substantially greater weight loss than liraglutide 3.0 mg in a head-to-head trial.
Side effects in brief
In the 2.4 mg weight-management trials the common effects were nausea in roughly 44%, diarrhoea in about 30%, vomiting and constipation each around 24%, abdominal pain around 20% and headache around 14%. Placebo groups reported gastrointestinal symptoms at meaningful rates too.
Most cases were mild to moderate and clustered in the days after a dose increase. The ones that need action rather than patience are severe persistent abdominal pain, vomiting that stops you keeping fluids down, and any sudden change in vision.
What it costs
Without insurance, list pricing runs well over a thousand dollars a month. Manufacturer cash-pay programmes and covered prescriptions land far lower. Coverage for weight management specifically is inconsistent between plans and usually requires prior authorisation.
Semaglutide was selected for Medicare price negotiation under the Inflation Reduction Act, with negotiated pricing scheduled to take effect in 2027. That is the single largest structural change coming to what this costs in the United States.
If you stop
The STEP 1 trial extension followed participants for a year after treatment ended. They regained about two thirds of the weight they had lost, and the improvements in blood pressure and lipids went largely with it.
That finding is the strongest argument for treating this as ongoing rather than temporary, and the strongest argument for making sure you can sustain the cost before you start.
Sources
- Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384(11):989-1002.
- Davies M, et al. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2). Lancet. 2021;397(10278):971-984.
- Garvey WT, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022;28(10):2083-2091.
- Rubino DM, et al. Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight (STEP 8). JAMA. 2022;327(2):138-150.
- Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564.
- Lincoff AM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med. 2023;389(24):2221-2232.
- Wegovy (semaglutide) injection, prescribing information. Novo Nordisk.
- Centers for Medicare & Medicaid Services, Medicare Drug Price Negotiation Program, second cycle selected drug list.