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Figure from article: Off-label treatment of obesity
 
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ABSTRACT
Introduction and objective:
Obesity is a global civilization disease driven by a positive caloric balance. It leads to severe comorbidities across all organ systems and increases mortality. Current treatment options, including lifestyle changes, surgery, and registered pharmacotherapy (e.g., orlistat, liraglutide), are often limited in efficacy or burdened with side effects. The objective of this review was to analyze the state of knowledge on obesity treatment and survey the most commonly used pharmacological agents.

Brief description of the state of knowledge:
GLP-1 analogues (e.g., semaglutide) are the most effective, enabling a 10–15% weight loss via central appetite suppression and delayed gastric emptying. Their main side effects are gastrointestinal. SGLT-2 inhibitors (flozins) induce a modest weight loss (1.5–3 kg) through glucosuria, but may increase appetite. They show additional cardiorenal benefits. Metformin contributes to mild weight reduction, potentially by modulating appetite and gut peptides. Berberine shows preclinical promise by improving lipid and glucose metabolism. The safety profile of GLP-1 agonists requires monitoring for rare pancreatitis risk, while SGLT-2 inhibitors commonly cause genital infections.

Summary:
A significant therapeutic gap exists in obesity management. GLP-1 receptor agonists, particularly semaglutide, represent a breakthrough with high efficacy. SGLT-2 inhibitors and metformin offer supportive, albeit milder, effects. These agents, used outside their primary indications, present a viable pharmacological strategy for weight reduction. However, their application must be balanced against side-effect profiles and the lack of official registration for obesity in many cases. Effective treatment extends beyond weight loss, improving overall quality of life and reducing the incidence of major metabolic diseases.
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