Semaglutide (Ozempic / Wegovy)

What semaglutide is

Semaglutide belongs to the GLP-1 receptor agonists, substances that mimic the action of a gut hormone the body makes itself. It is prescription-only and approved in the EU as Wegovy for weight management.

What is rated is the state of knowledge. Semaglutide is very well studied: large randomized trials, defined endpoints, ongoing post-marketing surveillance. That makes negative findings reliable as well.

How it works

The drug activates the GLP-1 receptor. Gastric emptying slows, satiety increases, insulin secretion improves and glucagon release drops. Food intake goes down, and the weight loss follows from that.

This chain of effects has been quantified in humans. What remains open is how much of the cardiovascular benefit is due to weight loss and how much to other effects.

What the studies show

SELECT: a hard endpoint, reached

Lincoff 2023 (NEJM) randomized 17,604 people aged 45 and older with a BMI of at least 27 and established cardiovascular disease, but without diabetes; mean follow-up 39.8 months. The primary endpoint of cardiovascular death, nonfatal heart attack and nonfatal stroke was reached: 6.5 percent versus 8.0 percent, hazard ratio 0.80 (95 percent confidence interval 0.72 to 0.90), p<0.001. This is not a lab value but an actual course of disease.

What the number means in absolute terms

The frequently cited 20 percent risk reduction is a relative figure. The difference between relative and absolute effect is considerable here: in absolute terms, 1.5 percentage points separate the two groups. Mathematically, this gives a number needed to treat of about 67 over 3.3 years, that is, about 67 people treated per event prevented. This value was calculated from the event rates and is not stated in the abstract. The trial also does not show that healthy people without prior disease benefit.

STEP 1: the weight effect

Wilding 2021 (NEJM) randomized 1,961 people over 68 weeks. Body weight fell by 14.9 percent versus 2.4 percent on placebo, difference 12.4 percentage points (11.5 to 13.4), p<0.001, corresponding to 15.3 kg versus 2.6 kg. A weight loss of at least 15 percent was reached by 50.5 percent versus 4.9 percent. Event endpoints were not collected in this trial.

After stopping

The STEP 1 extension (Wilding 2022, Diabetes Obes Metab) followed 327 people for one year after stopping. Of a 17.3 percent weight loss, 11.6 percentage points were regained; at week 120, a net 5.6 percent remained versus 0.1 percent. Cardiometabolic markers were largely back at baseline. The analysis was exploratory and concerned a non-randomized subset.

Where the data stop

• Benefit for healthy people without prior disease. SELECT enrolled only people aged 45 and older with a BMI of at least 27 and established cardiovascular disease. A benefit in people who do not meet these criteria has therefore not been shown.
• A lasting weight effect. One year after stopping, by far most of the loss had returned and cardiometabolic markers were largely back at baseline.
• Pure fat loss. With incretins, 33.3 percent of the weight lost was fat-free mass, versus 14.9 percent with diet and exercise. For semaglutide alone, 35.2 percent was reported. Targeted preservation of muscle mass is therefore not supported.
• Advertising with someone else's trial numbers. On the gray market, products are advertised with the results of the approval trials, although the same tested product is not what is sold there. The cited data apply to the approved medicine, not to goods of unclear origin.

Status, approval and legal situation

Wegovy was approved by the European Medicines Agency on 2022-01-06. The full approval documents are publicly available in the European public assessment report. The drug is prescription-only.

Since 2026-09-01, Wegovy has also been available as a tablet in German pharmacies; EU approval for it came in July 2026. For the treatment of obesity, semaglutide is not covered by German statutory health insurance (§ 34 SGB V); for type 2 diabetes, statutory insurance covers Ozempic and Rybelsus.

The US Food and Drug Administration (FDA) carries a boxed warning on C-cell tumors and medullary thyroid carcinoma. The drug is contraindicated with a corresponding personal or family history and in multiple endocrine neoplasia type 2.

Safety

In SELECT, 16.6 percent of those treated stopped therapy because of side effects, versus 8.2 percent on placebo, p<0.001 - a doubling, and under close trial supervision.

Added to this is the composition of the weight loss. A 2026 analysis puts the loss of fat-free mass with incretins at 4.8 kg (3.9 to 5.6), which corresponds to 33.3 percent of the weight lost, versus 14.9 percent with diet and exercise. The share is thus more than twice as high as with conventional weight loss.

Two further risks are known from meta-analyses and post-marketing surveillance. Diseases of the gallbladder and bile ducts occur more often with GLP-1 receptor agonists: a meta-analysis of 76 randomized trials with 103,371 people found a relative risk of 1.37 (1.23 to 1.52). Very rare is NAION, a circulatory disorder of the optic nerve; in June 2025, the safety committee of the European Medicines Agency classified it as a side effect of semaglutide, affecting up to 1 in 10,000 people treated. Sudden vision loss needs to be checked by a doctor immediately.

Sources

• Lincoff AM et al. 2023, NEJM - SELECT, cardiovascular endpoint (PMID 37952131)
• Wilding JPH et al. 2021, NEJM - STEP 1, weight loss (PMID 33567185)
• Wilding JPH et al. 2022, Diabetes Obes Metab - STEP 1 extension, discontinuation (PMID 35441470)
• Busk-Cirera A et al. 2026, Diabetes Obes Metab - loss of fat-free mass (PMID 42324178)
• Eisa M et al. 2026 - share of lean mass in weight loss (PMID 41877354)
• EMA - Wegovy, European public assessment report
• He L et al. 2022, JAMA Intern Med - gallbladder and biliary diseases with GLP-1 receptor agonists (PMID 35344001)
• EMA/PRAC, 2025-06-06 - NAION as a very rare side effect of Ozempic, Rybelsus and Wegovy