Semaglutide in the Therapy of Obesity: Mechanisms of Action

Nikita V. Pathophisiologist, MD

6 min read · January 29, 2026

This article is for informational purposes only

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One of the persistent and relevant issues in clinical medicine is the excessive body mass index (BMI) of patients, primarily due to excessive accumulation (increase in size and volume) of adipose tissue—commonly known as obesity.

Schematic representation of a person with obesity

Obesity is the result of a complex cascade of pathophysiological processes, which cannot be reduced solely to the overaccumulation of fat in the body and increased consumption of high-calorie, fatty food.

Studying and describing the exact mechanisms of obesity development allows modern medical science not only to understand the essence of this phenomenon but also to develop clinically effective medical therapy aimed at correcting this deviation.

Semaglutide: definition and mechanism of action

Currently, one of the most effective medications used for the treatment of obesity in patients is semaglutide (trade names: Ozempic®, Wegovy®, and Rybelsus®).

Semaglutide is a synthetic modified analog of glucagon-like peptide-1 (GLP-1). GLP-1 is a peptide hormone produced by specialized L-cells of the small intestine and indirectly involved in regulating many physiological processes in the human body.

Semaglutide exerts a GLP-1-like effect by binding to GLP-1 receptors, which specifically shows up as the activation of mechanisms leading to gradual and long-term correction of obesity.

Semaglutide’s impact on the brain

Thus, it is known that eating behavior disorders play an important role in increasing body mass index (BMI). Under physiological norms, different structural components of the hypothalamus produce certain substances involved in the formation of hunger and satiety signals as follows:

Agouti-related peptide (AgRP);
Neuropeptide Y (NPY);
Proopiomelanocortin (POMC);
Cocaine- and amphetamine-regulated transcript (CART).

Schematic representation of the neurophysiological centers of the hypothalamus regulating eating behavior, with visualization of neuropeptides stimulating hunger (NPY) And satiety (POMC and CART)

Changes in the frequency and nature of food intake can shift the existing balance of appetite-regulating substances towards either excessive food craving or sustained reluctance to eat.

Schematic representation of intermolecular interaction between semaglutide and GLP-1 receptors

The administration of semaglutide leads to the formation of a molecular bond between GLP-1 receptors located on the membranes of hypothalamic neurons and semaglutide.

The cascade of intracellular reactions triggered as a result leads to a decrease in the production of hunger-stimulating neuropeptides (specifically, neuropeptide Y) and, as a result, a relatively higher level of neuropeptides stimulating satiety.

In other words, semaglutide suppresses hunger in patients while simultaneously stimulating and prolonging satiety.

Another effect of semaglutide, realized at the nervous system level, is its effect on the vagus nerve. Modulation of its activity slows gastric motility, leading to prolonged food transit and reduced hunger.

Schematic representation of the “Brain – Vagus Nerve – Stomach” functional axis

3D Animation: impact of semaglutide on the brain

Semaglutide’s impact on the pancreas

In the context of pharmacological obesity therapy, the impact of semaglutide on the pancreas plays an important role.

It is known that one of the primary (but not the only) mechanisms of obesity development is persistent hyperglycemia, leading not only to obesity itself but also to diabetes mellitus and other systemic diseases.

Schematic representation of the microscopic structure of the islets of langerhans, producing hormonal regulators of glucose levels

Binding of semaglutide to the GLP-1 receptors of the islets of Langerhans in the pancreas leads, similarly to the regulation of eating behavior by the hypothalamus, to a decrease in glucagon production and a more significant action of insulin on the body.

Image description: functional activity of the islet cells of langerhans after semaglutide exposure — Functional activity of the islet cells of langerhans after semaglutide exposure

3D Animation: Semaglutide’s impact on the pancreas

Effect of Semaglutide on adipose tissue

In addition to these obvious mechanisms, semaglutide has additional ways of reducing adipose tissue volume.

Modulation of eating behavior and more sustained insulin action combined with reduced glucagon secretion leads to lower blood glucose levels and the creation of an energy deficit, forcing cells to seek alternative routes for energy production.

Schematic representation of a cell in an energy-deficient state

In this case, the primary source of energy becomes adipose tissue.

Triglycerides, accounting for most of the lipids contained within the vacuoles of adipose tissue cells, are broken down into their components: glycerol alcohol and fatty acids. Subsequently, both products of the breakdown reaction engage in their unique cascades of chemical transformations, culminating in the output of acetyl-CoA—a crossover molecule of all human metabolic pathways and a direct participant in one of the most crucial stages of energy production—the citric acid cycle.

Schematic structure of molecules participating in lipolysis: Triglycerides

Schematic structure of molecules participating in lipolysis: Acetyl-CoA

3D Animation: lipolysis as a consequence of Semaglutide use

Thus, semaglutide exerts a combined effect on the human body concerning its role in obesity treatment. By acting on GLP-1 receptors in the brain and pancreas, it contributes to reducing hunger and maintaining a normal blood glucose level.

Through such effects, semaglutide also aids in reducing adipose tissue due to the forced mobilization of stored triglycerides for energy production.

FAQ

1. Is Semaglutide a hormone or not?

Semaglutide is a synthetic modified analog of glucagon-like peptide-1 (GLP-1), a natural peptide hormone produced by intestinal cells. Although the drug is laboratory-produced, it fully mimics the action of a natural hormone in the body, binding to the appropriate receptors and participating in regulating glucose levels and satiety processes.

2. How does Semaglutide help in weight reduction?

The drug acts on specific receptors in the hypothalamus, altering the balance of neuropeptides towards those stimulating satiety and suppressing the production of hunger-inducing substances. Moreover, it slows gastric motility through its impact on the vagus nerve and optimizes pancreatic function, collectively creating an energy deficit that compels the body to break down stored adipose tissue for metabolic needs.

3. What is the instruction for use of Semaglutide?

The drug is administered subcutaneously once a week in the abdomen, thigh, or arm, with the time of food intake not affecting its effectiveness. The therapeutic course usually begins with a minimum dosage of 0.25 mg for gradual body adaptation, followed by an increase in dose every four weeks according to the regimen prescribed by the doctor. When using the tablet form, the drug is taken on an empty stomach with a small amount of water, at least 30 minutes before the first meal or other medications.

4. Are there any side effects from taking the medication?

The most common adverse reactions are related to the gastrointestinal tract, manifesting as nausea, vomiting, diarrhea, or constipation, particularly during dose escalation. Some patients may experience abdominal pain, general weakness, reduced appetite, and flatulence, which usually resolve independently as the body adapts. In rare cases, serious complications such as pancreatitis, gallbladder changes, or allergic reactions may occur, necessitating immediate consultation with a specialist.

5. When does the medication begin to act?

The pharmacological action at the receptor level starts shortly after the first dose is administered, but the visible clinical effect in the form of stable weight loss and changes in dietary habits usually appears after several weeks of regular use. Achieving significant results in obesity therapy requires gradual body adaptation and adherence to a long-term injection schedule as provided by instructions.

6. Which drug products contain Semaglutide and are there any alternatives?

On the pharmaceutical market, semaglutide is presented under well-known trade names such as Ozempic and Wegovy (injection forms), and Rybelsus (tablet form). Analogs from the group of GLP-1 receptor agonists include drug products based on liraglutide, dulaglutide, or exenatide, but the choice of a specific agent and its effectiveness assessment should be carried out strictly by the attending physician based on the patient’s clinical presentation.

7. What are the contraindications for Semaglutide use?

The primary contraindications include the presence of medullary thyroid carcinoma in personal or family history, multiple endocrine neoplasia type 2 syndrome, as well as severe renal function disorders and individual hypersensitivity to any of the drug product’s components. Such a therapy is not recommended during pregnancy and lactation; patients with pancreatic diseases, such as pancreatitis, require special caution and preliminary examination before initiating the course.

References

VOKA 3D Anatomy & Pathology – Complete Anatomy and Pathology 3D Atlas [Internet]. VOKA 3D Anatomy & Pathology.

Available from: https://catalog.voka.io/

Chao, Ariana M., et al. “Semaglutide for the Treatment of Obesity.” Trends in Cardiovascular Medicine, vol. 33,3 (2023): 159-166. DOI:10.1016/j.tcm.2021.12.008

Gabery, Sanaz, et al. “Semaglutide Lowers Body Weight in Rodents via Distributed Neural Pathways.” JCI insight vol. 5,6 e133429. 26 Mar. 2020, DOI:10.1172/jci.insight.133429

Smits, Mark M, and Daniël H Van Raalte. “Safety of Semaglutide.” Frontiers in endocrinology vol. 12 645563. 7 Jul. 2021, DOI:10.3389/fendo.2021.645563