Semaglutide

Semaglutide is a GLP-1 receptor agonist approved by the FDA for type 2 diabetes (Ozempic) and chronic weight management (Wegovy). It is among the most prescribed and searched compounds in the weight loss space. Compounding pharmacies produced semaglutide formulations under the 503A and 503B frameworks while semaglutide injection was on the FDA drug shortage list; that pathway has since closed (see access and regulatory status below). Mechanism of action: Semaglutide activates glucagon-like peptide-1 (GLP-1) receptors in the hypothalamus, brainstem, and pancreas. This triggers a coordinated metabolic response: appetite signals are reduced, gastric emptying is slowed (increasing satiety duration), insulin secretion is potentiated in a glucose-dependent manner, and glucagon secretion is suppressed. The result is reduced caloric intake and improved postprandial glucose regulation. Semaglutide's extended half-life (~7 days) enables once-weekly subcutaneous injection, distinguishing it from earlier GLP-1 agonists that required daily dosing. Clinical evidence: The STEP trial program established semaglutide's weight reduction profile. STEP 1 (2021) found a mean weight reduction of 14.9% over 68 weeks with 2.4mg/week semaglutide (Wegovy dose) vs 2.4% with placebo. STEP 4 demonstrated that discontinuation led to weight regain, indicating ongoing use is required to maintain outcomes. The SUSTAIN trial series confirmed cardiovascular risk reduction in T2D patients. Semaglutide is one of the most extensively studied GLP-1 agonists in large-scale randomised controlled trials. Semaglutide with B12: Some compounded formulations combined semaglutide with vitamin B12 (methylcobalamin) in the same injectable preparation. The rationale is two-fold: nausea and gastrointestinal discomfort are the most commonly reported side effects of GLP-1 agonists (occurring in 15–40% of users in trials), and injectable methylcobalamin bypasses the reduced gastric absorption that can accompany slowed gastric motility. B12 also supports energy metabolism during periods of caloric restriction. Clinical evidence that B12 addition changes weight loss outcomes is limited; the combination is primarily a compounding convention rather than a protocol validated in independent clinical trials. The FDA has stated that it may consider a compounded drug product combining semaglutide API and another API, such as vitamin B12 (cyanocobalamin), to be essentially a copy of a commercially available drug product where the drug products are used by the same route of administration and the amounts of semaglutide and vitamin B12 in the compounded product are within 10% of the strengths of the respective commercially available drug products. Semaglutide vs tirzepatide: Semaglutide is a single GLP-1 receptor agonist; tirzepatide is a dual agonist targeting both GLP-1 and GIP receptors. The SURMOUNT-5 head-to-head trial found tirzepatide produced greater weight reductions than semaglutide at comparable doses. Both are FDA-approved and available through licensed prescribers; protocol selection depends on clinical context and provider judgment. Access and regulatory status: Semaglutide requires a prescription from a licensed provider. Branded formulations (Ozempic, Wegovy) are available at licensed pharmacies. Compounded semaglutide was permitted only while semaglutide injection appeared on the FDA drug shortage list. After the FDA determined that shortage resolved, it stated that its period of enforcement discretion would run until 22 April 2025 for state-licensed pharmacies and physicians compounding under section 503A of the FD&C Act, and until 22 May 2025 for outsourcing facilities under section 503B; on 24 April 2025 the district court denied the plaintiffs' preliminary injunction motion in Outsourcing Facilities Association v. FDA (N.D. Tex.), and the FDA has since confirmed that the 503A period has ended. As of the FDA's 1 April 2026 statement, semaglutide does not appear on the 503B bulks list or on the FDA drug shortage list, so compounded semaglutide that is essentially a copy of an FDA-approved product no longer has a lawful shortage-based route. On 3 March 2026 the FDA announced the issuance of 30 warning letters to telehealth companies for making false or misleading claims regarding compounded GLP-1 products offered on their websites; the primary violations it identified included making claims implying sameness with FDA-approved products and obscuring product sourcing by advertising drug products branded with the telehealth firm's name or trademark without qualification, implying they are the compounder. Regulatory status verified against FDA sources on 25 July 2026.