Semaglutide

What it is

Semaglutide is a long-acting GLP-1 receptor agonist — a molecule that mimics the gut hormone GLP-1 to increase insulin secretion when glucose is high, slow gastric emptying, and reduce appetite. Its structure resists rapid breakdown, giving it a roughly one-week half-life that supports once-weekly injection (Ozempic, Wegovy) or a daily oral tablet (Rybelsus).

What it’s approved or studied for

Semaglutide is FDA-approved for type 2 diabetes (Ozempic, Rybelsus), chronic weight management in adults with obesity or overweight-plus-a-comorbidity (Wegovy), and — following the SELECT trial — cardiovascular risk reduction in specific populations. It has, by a wide margin, the largest randomized human evidence base of any peptide covered on this site.

What human evidence exists

The pivotal trials are large, randomized, and placebo-controlled. The STEP program established the weight-loss effect; the SUSTAIN program established glycemic benefit; and SELECT (2023) extended the cardiovascular evidence into people with obesity but without diabetes. This is Grade A evidence for its core outcomes.

The major unknowns

Long-term (multi-decade) safety data are still accumulating, the durability of weight loss after stopping is limited (weight regain is common), and the lean-mass cost of rapid loss is real. Compounded semaglutide sold outside the approved supply chain is not the same product from an evidence or quality standpoint.

Most important safety considerations

Gastrointestinal side effects are common and usually improve with slow titration. The boxed warning for thyroid C-cell tumors is based on rodent data; a personal or family history of medullary thyroid carcinoma or MEN 2 is a contraindication. Discuss any GLP-1 therapy with a clinician — this page is a research summary, not medical advice.