Semaglutide is a GLP-1 receptor agonist from Novo Nordisk. It is FDA-approved as Ozempic and Rybelsus for type 2 diabetes, and as Wegovy for chronic weight management and for lowering the risk of heart attack and stroke in people with heart disease and excess weight.[1][2][3] In its main obesity trial, people on semaglutide lost an average of 14.9% of their body weight over 68 weeks.[8]
This profile covers how semaglutide works, its FDA approvals, the key trials and its side effects. See also our profiles of tirzepatide and retatrutide.
What is semaglutide?
Semaglutide is a long-acting synthetic peptide that works like the body’s own GLP-1 hormone.[1] It is sold under three brand names:
- Ozempic (weekly injection): approved in December 2017 for blood sugar control in type 2 diabetes.[4] Its label also covers lowering cardiovascular risk in people with type 2 diabetes and heart disease, and lowering kidney and cardiovascular risk in people with type 2 diabetes and chronic kidney disease.[1]
- Rybelsus (daily tablet): approved in September 2019 for type 2 diabetes.[5][3]
- Wegovy (weekly injection): approved in June 2021 for chronic weight management, and in March 2024 to reduce the risk of cardiovascular death, heart attack and stroke in adults with cardiovascular disease and obesity or overweight.[6][7] It is also approved for weight management in adolescents aged 12 and older with obesity.[2]
How semaglutide works
Semaglutide activates the GLP-1 receptor, the target of a gut hormone involved in appetite and insulin release.[1] Its half-life is about one week, which allows once-weekly injections.[1]
Newer drugs build on the same approach: tirzepatide also activates the GIP receptor, and the investigational retatrutide adds the glucagon receptor as well.
Clinical trial results
Weight loss: STEP 1
STEP 1 enrolled adults with obesity, or overweight plus a weight-related condition, who did not have diabetes.[8]
| Outcome at 68 weeks | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Average weight change | −14.9% | −2.4% |
| Lost 5% or more | 86.4% | 31.5% |
| Lost 10% or more | 69.1% | 12.0% |
| Lost 15% or more | 50.5% | 4.9% |
Heart protection without diabetes: SELECT
SELECT followed 17,604 adults with existing cardiovascular disease and overweight or obesity, but no diabetes, for an average of 39.8 months. Cardiovascular death, heart attack or stroke occurred in 6.5% of people on semaglutide 2.4 mg versus 8.0% on placebo, a 20% lower risk.[10] This trial supported the 2024 Wegovy approval for cardiovascular risk reduction.[7]
Heart outcomes in type 2 diabetes: SUSTAIN-6
In 3,297 adults with type 2 diabetes at high cardiovascular risk, cardiovascular death, heart attack or stroke occurred in 6.6% on semaglutide versus 8.9% on placebo.[9]
Side effects
- Gastrointestinal effects were the most common. In STEP 1, nausea and diarrhea led the list; they were usually mild to moderate and eased over time.[8]
- Stopping because of side effects: in STEP 1, 4.5% stopped because of gastrointestinal effects, versus 0.8% on placebo.[8] In the longer SELECT trial, 16.6% stopped because of any adverse event, versus 8.2% on placebo.[10]
- Diabetic eye disease: in SUSTAIN-6, complications of diabetic retinopathy were more common with semaglutide than with placebo.[9]
Boxed warning: the label warns that semaglutide caused thyroid C-cell tumors in rodents. It is unknown whether it causes these tumors, including medullary thyroid carcinoma, in humans.[1] Read the full Ozempic and Wegovy prescribing information for all warnings.
Doses studied
STEP 1 and SELECT tested semaglutide 2.4 mg once a week, the Wegovy maintenance dose.[8][10] Your prescriber decides the dose and how quickly to increase it, following the prescribing information for the product you use.
Semaglutide vs tirzepatide and retatrutide
Semaglutide has the longest track record of the three, including completed cardiovascular outcome trials. The newer drugs reported larger weight loss in their own trials, but comparing separate trials is unreliable because the populations and methods differ. See our tirzepatide and retatrutide profiles for each drug’s evidence.