Semaglutide

Semaglutide is a synthetic peptide derived from the naturally occurring hormone glucagon-like peptide-1 (GLP-1). It is composed of 31 amino acids and is designed to mimic the effects of GLP-1 in the human body. Its structure allows it to have a longer duration of action compared to natural GLP-1.

Semaglutide is primarily used to support weight management and improve blood sugar control in individuals with type 2 diabetes. It has been shown to reduce appetite, promote feelings of fullness, and lower levels of glucose in the bloodstream. These effects make it useful for metabolic health and weight reduction.

Semaglutide has been shown in multiple randomized controlled trials and meta‑analyses to produce large and sustained weight loss. In non‑diabetic individuals with overweight or obesity, semaglutide reduced body weight on average by about 10 %, lowered BMI by approximately 3.7 kg/m², and shrank waist circumference by over 8 cm compared to placebo. In long‑term follow‑up studies lasting at least 68 weeks, once‑weekly semaglutide led to mean relative weight loss of over 12 % ^{1, 2}.

Beyond weight loss, semaglutide improves cardiometabolic risk by reducing major adverse cardiovascular events (MACE). In analyses of SUSTAIN‑6 and PIONEER‑6 trials in people with type 2 diabetes, semaglutide lowered the risk of cardiovascular death, stroke, or heart attack. A prespecified analysis of the SELECT trial showed that, even in people without diabetes but with obesity, semaglutide reduced the risk of MACE by about 20 % after 33 months ^{3, 4}. In short, Semaglutide provides strong benefits in weight loss and in lowering cardiovascular risk.

Semaglutide commonly causes gastrointestinal side effects. Clinical trials and meta‑analyses report nausea in a large fraction of users, along with vomiting, diarrhea, abdominal pain, and constipation. These symptoms are typically mild to moderate and often decrease over time, but they are a frequent reason for treatment discontinuation ^{5, 6}. Beyond GI issues, semaglutide is associated with other risks. Because it lowers blood sugar, it can trigger hypoglycemia, especially when used with other glucose‑lowering drugs like insulin or sulfonylureas. It also increases the risk of gallbladder-related problems such as cholelithiasis (gallstones). While earlier concerns about pancreatitis have been raised, a recent meta-analysis of 21 randomized‑controlled trials found no clear increase in risk ^{7, 8, 9}.

Another import note is Semaglutide can lead to muscle (lean‑mass) loss in some individuals. In animal studies, mice treated with semaglutide lost skeletal muscle mass and strength to a similar degree as mice under calorie restriction. In a retrospective cohort of older adults with type 2 diabetes, those on semaglutide showed significant declines in appendicular skeletal muscle mass over 24 months, along with reduced gait speed and, in women, decreasing grip strength ^{10, 11}. On the other hand, some clinical work suggests that muscle loss might be modest or offset. A 24‑week study of oral semaglutide in Japanese patients found significant fat mass reduction but no statistically significant drop in lean mass as measured by bioelectrical impedance ¹². Overall, while semaglutide provides substantial benefits for weight and glucose management, its potential gastrointestinal effects, risk of hypoglycemia, gallbladder issues, and possible impact on muscle mass highlight the importance of monitoring during usage.

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that mimics the action of native GLP-1 by binding to its receptors. Activation of these receptors increases cAMP in pancreatic beta cells, which stimulates pathways that enhance glucose-dependent insulin production and secretion. At the same time, semaglutide reduces glucagon release from alpha cells, slows gastric emptying, and influences brain regions that control appetite. These combined effects help regulate blood sugar levels and reduce food intake. Studies in humans and animals have shown that semaglutide also improves insulin sensitivity and promotes weight loss by decreasing energy intake. Its action on central appetite pathways contributes to a sustained reduction in body weight over time ^{13, 14} 15(https://pmc.ncbi.nlm.nih.gov/articles/PMC8736331/).

Semaglutide is FDA‑approved for human use in the United States and is available by prescription under brand names such as Ozempic, Wegovy, and Rybelsus. While compounded versions of semaglutide were temporarily allowed during periods of shortage under FDA discretion, these compounded forms are not fully FDA‑approved, and the FDA has issued warnings against unapproved compounded products. In athletic contexts, semaglutide is not currently on the WADA Prohibited List, but it is included on WADA’s Monitoring Program. This means that anti-doping authorities are observing its use, although it is not prohibited in sports at present.