Semaglutide for weight loss: How the medical treatment works

What is semaglutide and how does it work in the body?

Semaglutide is an active pharmaceutical substance belonging to the group of GLP-1 receptor agonists. It works by mimicking the effect of the body's own intestinal hormone GLP-1 (glucagon-like peptide-1), which affects appetite regulation, satiety, and glucose metabolism.

Upon food intake, GLP-1 is naturally released from the small intestine and signals to the brain that energy has been supplied to the body. However, the hormone has a very short half-life and is quickly broken down in the body. Semaglutide is structurally modified to resist this breakdown, providing a more long-lasting effect on the body's appetite and energy regulation.

The treatment affects the body through several interacting mechanisms:

• Central appetite regulation: Semaglutide activates GLP-1 receptors in the brain's appetite center, which reduces hunger and increases the feeling of satiety.
• Delayed gastric emptying: The medicine slows down the emptying of the stomach, which contributes to more long-lasting satiety after a meal.
• Glucose-dependent insulin release: Semaglutide stimulates insulin secretion in connection with meals and contributes to improved blood sugar control.

Semaglutide is used in the treatment of type 2 diabetes as well as obesity and overweight. For optimal effect, treatment should be combined with lifestyle measures, such as dietary changes and increased physical activity.

Medicines by Novo Nordisk: Wegovy, Ozempic, and Rybelsus – what is the difference?

All of these preparations are manufactured by the Danish pharmaceutical company Novo Nordisk, but they differ regarding approved indication and how they are administered.

• Wegovy: Given as a subcutaneous injection (shot into the subcutaneous fat) once a week. This medicine is approved for the treatment of obesity and overweight with weight-related complications.
• Ozempic: Given as a subcutaneous injection once a week and is approved for the treatment of type 2 diabetes.
• Rybelsus: Contains semaglutide in tablet form and is taken daily. This medicine is also primarily approved for type 2 diabetes but can serve as an alternative for patients with, for example, a pronounced fear of needles.

All medicines contain the same active substance, semaglutide, and thus have the same basic mechanisms of action. The decisive difference lies in dosage, form of administration, and approved use.

When treating overweight or obesity without concurrent type 2 diabetes, Wegovy is approved and is generally the first choice. Prescribing Ozempic or Rybelsus solely for weight loss constitutes use outside the approved indication (off-label) and requires an individual medical assessment where benefits and risks must be carefully considered.

What results can be expected from the treatment?

In large clinical studies, treatment with semaglutide (Wegovy) has shown an average weight loss of approximately 15 percent of body weight after about 68 weeks, in combination with lifestyle support.

Participants who received active treatment achieved significantly greater weight reduction compared to the placebo group, and a significant proportion reached clinically relevant weight loss levels. Weight loss of this magnitude is associated with improvements in several cardiometabolic risk factors, such as blood pressure, blood lipids, and glucose metabolism.

It is well established that even a weight loss of 5–10 percent can lead to clinically significant improvements in cardiovascular risk markers.

Drug treatment is effective in itself. However, the best and most sustainable results are achieved in combination with lifestyle habits. Semaglutide acts as a biological support by affecting appetite regulation and energy intake, but long-term results depend on the treatment being combined with sustainable lifestyle habits, including structured support regarding diet and regular physical activity.

Common side effects of semaglutide and how to handle them

The most common side effects of treatment with semaglutide are gastrointestinal and include nausea, diarrhea, and constipation. These symptoms are usually mild to moderate and occur mainly at the beginning of treatment or in connection with dose escalation.

Because the medicine affects the function of the gastrointestinal tract, including by delaying gastric emptying, these side effects are expected during the initial treatment phase. To improve tolerability, treatment begins with a low starting dose that is gradually increased.

The discomfort can often be alleviated through adjustments in daily life:

• Adjust portion sizes: Smaller meals and stopping at early satiety signals can reduce the risk of nausea.
• Avoid fatty and heavy food: High-fat or hard-to-digest diets can exacerbate gastrointestinal symptoms.
• Ensure adequate fluid intake: A steady fluid intake can help counteract constipation.

In rare cases, more serious side effects have been reported, such as pancreatitis and gallstone disease. Patients should therefore be informed about symptoms such as persistent abdominal pain, especially if it radiates toward the back, and be urged to seek care for such complaints.

Why protein and strength training are important during weight loss

To optimize body composition during weight loss, it is important to combine the treatment with an adequate protein intake and regular strength training. The goal is to preserve muscle mass as much as possible while reducing fat mass.

In an energy deficit, the body uses both fat and muscle tissue as an energy source. Without sufficient stimulation, there is a risk that part of the weight loss will consist of loss of muscle mass. Such a change in body composition can, in the long run, affect physical function and metabolic health.

Strength training acts as a signal to the body to preserve musculature, while a sufficient protein intake provides the amino acids required to maintain and repair muscle tissue. Together, these factors contribute to a more favorable distribution between fat and muscle mass during weight loss.

Preserved muscle mass is also important for basal energy expenditure, which can facilitate weight stability over time. Against this background, it is recommended that protein intake be distributed evenly over the day's meals and that strength training be included regularly, adapted to individual conditions and ability.

Who can get semaglutide prescribed for overweight?

Treatment may be relevant at a BMI of at least 30, or a BMI of 27 in combination with at least one weight-related complication such as high blood pressure, dyslipidemia (elevated blood lipids), or obstructive sleep apnea.

The decision to prescribe is always preceded by an individual assessment by a licensed physician. The investigation is based on your health history, other diseases, previous attempts at weight loss, and current blood tests, to ensure that the treatment is medically safe for your specific biology.

Frequently asked questions about semaglutide

Is it legal to buy semaglutide without a prescription?

Medicines containing semaglutide are prescription-only within the EU and may only be prescribed by licensed healthcare professionals after a medical assessment.

Buying such medicines without a prescription, for example via unregulated online actors, involves significant risks. The products may lack quality control, have an unknown composition, or be incorrectly dosed, which can lead to serious health consequences.

Does it hurt to take the injection?

Most patients experience the injection as very little painful or, in practice, painless. The medicine is administered with a pre-filled pen equipped with a very thin and short needle, which is injected superficially into the subcutaneous fat.

Since subcutaneous fat generally has fewer pain receptors than the skin, the injection is usually felt as a light prick or a brief discomfort. Individual experiences may, however, vary.

What happens if I forget to take my dose?

Semaglutide as an injection (e.g., Wegovy or Ozempic, weekly dose):

If you miss a weekly dose, you can take it as soon as you remember, provided there are at least 48 hours left until the next planned dose. If there are less than 48 hours left, skip the missed dose and continue according to your usual schedule. You should not take a double dose.

Rybelsus (tablet, daily dose):

If you forget to take your daily dose, skip the missed dose and take the next tablet as usual the next day. You should not take a double dose to compensate, as this can increase the risk of side effects without improving the effect.

Can I drink alcohol during the treatment?

Alcohol can be consumed in moderate amounts during treatment with semaglutide, but should be ingested with caution.

Semaglutide affects the function of the gastrointestinal tract and can delay gastric emptying, which in some individuals can exacerbate gastrointestinal side effects such as nausea. Alcohol can further contribute to such complaints and should therefore be limited, especially at the beginning of treatment or when increasing the dose.

For people with type 2 diabetes, it is also important to be aware that alcohol can affect blood sugar levels.

Overall, a moderate intake is recommended, and to be attentive to how the body reacts. In case of uncertainty or pronounced side effects, you should consult your healthcare provider.

Do I need to take semaglutide for the rest of my life?

Since obesity is a chronic disease, the body has a biological tendency to return to a higher weight after weight loss. For many patients, this means that a long-term treatment strategy may be necessary to maintain the results.

How long the treatment needs to last is individual and depends, among other things, on treatment response, goal fulfillment, and any side effects.

The decision on treatment length should be made in consultation with the treating physician, focusing on achieving and maintaining good and sustainable health over time.

Sources

The New England Journal of Medicine. Once-Weekly Semaglutide in Adults with Overweight or Obesity. https://www.nejm.org/doi/full/10.1056/NEJMoa2032183

European Medicines Agency (EMA). Wegovy (semaglutide) – EPAR Product Information. https://www.ema.europa.eu/en/medicines/human/EPAR/wegovy

European Medicines Agency (EMA). Ozempic (semaglutide) – EPAR Product Information. https://www.ema.europa.eu/en/medicines/human/EPAR/ozempic

The Lancet. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity. https://pubmed.ncbi.nlm.nih.gov/37385278/

The Lancet Diabetes & Endocrinology. Muscle matters: the effects of medically induced weight loss on skeletal muscle. https://pubmed.ncbi.nlm.nih.gov/39265590/