Semaglutide

Definition

Semaglutide is a GLP-1 receptor agonist, a modified analogue of the gut hormone glucagon-like peptide-1 engineered for once-weekly subcutaneous dosing; an oral formulation is marketed separately. It is approved in the United States for type 2 diabetes and, at a higher dose, for chronic weight management.

The molecule slows gastric emptying, augments glucose-dependent insulin secretion, and acts on central appetite circuits; the weight effect is a drug effect, not a property of the injection route.

Evidence

In the pivotal STEP 1 trial, 1,961 adults with overweight or obesity received once-weekly semaglutide 2.4 mg or placebo; mean weight change at week 68 was −14.9 percent against −2.4 percent with placebo, and half of treated participants lost 15 percent or more ^[1].

The evidence base is unusually deep for this index; the open questions concern durability after discontinuation and long-term use outside trial conditions rather than whether the drug works.

Withdrawal is a separate question from initial weight loss. The STEP 1 extension followed a selected subset after both medication and structured lifestyle support ended; STEP 4 randomized eligible run-in completers to continue medication or switch to placebo while lifestyle support continued. Both found regain after withdrawal, but their percentages use different starting points ^{[9, 10]}. The withdrawal evidence review explains those denominators and why neither study supplies a tapering protocol.

Side effects

The Wegovy label lists the adverse reactions reported in at least 5 percent of treated patients: nausea, diarrhea, vomiting, constipation, abdominal pain, dysesthesia, headache, fatigue, dyspepsia, dizziness, abdominal distension, belching, flatulence, gastroenteritis, gastroesophageal reflux and hair loss, with hypoglycemia among patients who also have type 2 diabetes ^[3]. Most are gastrointestinal, and the label notes that gastrointestinal reactions are sometimes severe; it does not recommend the drug for people with severe gastroparesis ^[3].

The label carries a boxed warning for thyroid C-cell tumors: semaglutide caused them in mice and rats, whether it does so in humans is unknown, and the drug is contraindicated for anyone with a personal or family history of medullary thyroid carcinoma or with multiple endocrine neoplasia syndrome type 2 ^[3].

Its other warnings cover acute pancreatitis, acute gallbladder disease, hypoglycemia when combined with insulin or an insulin secretagogue, acute kidney injury from dehydration, serious allergic reactions including anaphylaxis and angioedema, diabetic retinopathy complications in patients with type 2 diabetes, an increased heart rate, and pulmonary aspiration during general anesthesia or deep sedation ^[3].

Compounded semaglutide is not covered by that label. The FDA has received adverse event reports, some requiring hospitalization, linked to dosing errors with compounded injectable semaglutide, where patients or clinicians measured the wrong amount ^[4].

Educational summary of the cited sources, not medical advice; a prescriber weighs these risks against a person’s own history.

Lawful access

The approved products are the lawful supply route. Mass compounding ended after the FDA declared the shortage resolved; in April 2026 the agency proposed excluding semaglutide from the 503B bulks list, and the remaining 503A path requires a prescriber to document a clinical need an approved product cannot meet — a lower price does not qualify ^[2].

Telehealth programs in the supply panel provide prescriber-led GLP-1 treatment; the specific molecule and formulation offered vary by provider and should be confirmed on the provider's own site.

Related molecules

Semaglutide shares its class and its regulatory shape with tirzepatide; the GLP-1 receptor agonists page compares the class, and the approved status page lists every approved molecule in this index.

Semaglutide is also half of CagriSema, Novo Nordisk's investigational weekly combination of semaglutide with cagrilintide, a long-acting amylin analogue; the company submitted it to the FDA in December 2025 ^[5] and lists a US decision among its milestones for the fourth quarter of 2026 ^[7]. In REDEFINE 4, an open-label phase 3 trial against tirzepatide, CagriSema did not show non-inferiority on weight loss at 84 weeks ^[6]. The same company's zenagamtide, also known as amycretin, is a single peptide acting at both the GLP-1 and amylin receptors ^[8], and its AMAZE phase 3 program is under way ^[7]. The incretin pipeline tracker sets these candidates beside the approved drugs.

Elsewhere in this index