SEMAGLUTIDA (GLP-1)

Mechanism of Action
Semaglutide is an analog of glucagon-like peptide-1 (GLP-1) that acts as a GLP-1 receptor agonist. By binding to this receptor, it stimulates glucose-dependent insulin secretion—particularly when blood glucose levels are elevated—and suppresses glucagon release from the pancreas. In addition, it slows gastric emptying, prolonging digestion, and acts centrally to reduce appetite and increase satiety. Together, these effects reduce caloric intake and promote weight loss.
These actions mimic those of natural incretins (intestinal hormones that regulate blood glucose), explaining semaglutide’s benefits in both glycemic control and weight management. Furthermore, activation of GLP-1 receptors in peripheral tissues and the central nervous system contributes to improved energy homeostasis, enhanced insulin sensitivity, and may exert anti-inflammatory and cardioprotective effects, according to recent studies.
 
Clinical Uses
Semaglutide is approved for the treatment of type 2 diabetes mellitus as a second-line therapy (or first-line in certain cases) to improve glycemic control in patients who do not achieve adequate targets with lifestyle modifications alone. Owing to its metabolic effects, it is also used for the management of obesity: at higher doses (2.4 mg weekly, commercially formulated as Wegovy®), it is indicated as a chronic treatment for weight loss in adults with obesity or overweight who have weight-related comorbidities.
Beyond lowering blood glucose, semaglutide has demonstrated cardiovascular benefits. In patients with type 2 diabetes and established cardiovascular disease, its use reduces the risk of major adverse cardiovascular events such as myocardial infarction, stroke, or cardiovascular death. More recently, a large clinical trial in patients with obesity (without diabetes) showed that semaglutide also significantly reduces the risk of cardiovascular events in individuals with obesity and pre-existing cardiovascular disease. Additionally, in certain patients with type 2 diabetes and diabetic nephropathy, semaglutide has been observed to slow the progression of kidney disease.
In summary, its clinical uses include glycemic control in type 2 diabetes, reduction of cardiovascular risk in high-risk populations (people with diabetes and those with obesity and cardiovascular disease), and adjunctive treatment to achieve substantial weight loss in obesity.
 
Side Effects and Safety
Like other GLP-1 receptor agonists, semaglutide primarily causes gastrointestinal side effects. The most common are nausea, vomiting, diarrhea, as well as abdominal discomfort or pain, constipation, and reflux-type symptoms (belching, heartburn). These effects typically occur at the start of treatment and tend to diminish over time as the body adapts; initiating therapy at low doses and gradually increasing them helps improve tolerability.
Nevertheless, a small percentage of patients do not tolerate these symptoms and may discontinue treatment. In the STEP 1 trial with semaglutide 2.4 mg, approximately 4.5% of patients discontinued the drug due to gastrointestinal adverse events, compared with 0.8% in the placebo group.