Semaglutide & Tirzepatide – Brand-Name and Compounded Formulations
The FDA resolved the nationwide shortage of tirzepatide on December 19, 2024 and semaglutide on February 21, 2025. Compounded versions of these medications may now only be prescribed when a prescriber documents a patient-specific significant difference justifying why the commercially available product is not appropriate for the individual patient, pursuant to FDCA Section 503A(b)(2). On February 6, 2026, the FDA announced that entities engaged in the manufacture, distribution, or marketing of unapproved compounded GLP-1 products may face legal action including seizure and injunction without further notice. A separate Clinical Difference Attestation must accompany this consent when compounded GLP-1 medications are prescribed.
This document provides information about GLP-1 receptor agonist medications that may be prescribed as part of your weight management or metabolic health treatment. GLP-1 receptor agonists include semaglutide (brand names: Ozempic, Wegovy, Rybelsus) and tirzepatide (brand names: Mounjaro, Zepbound). These medications may be prescribed in their FDA-approved brand-name form or, where legally permitted, as compounded formulations prepared by a licensed compounding pharmacy.
FDA-Approved Brand-Name Products: Ozempic and Rybelsus are approved for type 2 diabetes. Wegovy is approved for chronic weight management. Mounjaro is approved for type 2 diabetes. Zepbound is approved for chronic weight management. If your prescriber uses any of these products for a purpose other than its FDA-approved indication (e.g., Ozempic for weight loss), this constitutes off-label use.
Compounded Formulations: Compounded semaglutide and tirzepatide are prepared by licensed compounding pharmacies under FDCA Section 503A or 503B. Compounded medications are NOT FDA-approved, have NOT undergone FDA review for safety, efficacy, or manufacturing quality, and may differ from brand-name products in formulation, concentration, and inactive ingredients (excipients).
Semaglutide sodium and semaglutide acetate are PROHIBITED salt forms. The FDA determined on February 4, 2026 that these are different active ingredients than semaglutide base and there is no lawful basis for their use in compounding. Your prescriber should only use semaglutide base (not sodium or acetate salt) or tirzepatide base from a licensed compounding pharmacy. Retatrutide and cagrilintide also cannot be used in compounding.
Following the resolution of FDA-recognized shortages, compounded GLP-1 medications may only be legally prescribed under Section 503A when your prescriber determines, through individualized clinical assessment, that a change between the compounded and commercially available product produces a “significant difference” for you specifically. This must be documented on the prescription and in a separate Clinical Difference Attestation form. Price alone is never a sufficient justification. Acceptable significant differences may include:
Note: California imposes a heightened standard requiring a “clinically significant difference” (effective June 17, 2025), with an additional pharmacist verification duty. Your prescriber will advise if state-specific requirements apply.
Common Side Effects (reported in 10%+ of patients):
Serious Risks (less common but medically significant):
GLP-1 receptor agonists delay gastric emptying, which increases the risk of pulmonary aspiration during anesthesia. The American Society of Anesthesiologists has issued preoperative management guidance. YOU MUST INFORM YOUR ANESTHESIOLOGIST AND SURGEON that you are taking a GLP-1 medication before any procedure requiring sedation or general anesthesia. Your prescriber may advise you to hold doses before scheduled procedures.
GLP-1 receptor agonists are intended as long-term treatment. Clinical trial data demonstrates significant weight regain after discontinuation. The STEP 1 extension trial showed patients regained approximately two-thirds of lost weight within one year of stopping semaglutide. SURMOUNT-4 showed an average 14% weight regain after tirzepatide discontinuation. A 2025 BMJ systematic review found average regain of 9.9 kg in the first year, with projected return to baseline weight by approximately 1.5 years. Discuss long-term treatment planning with your prescriber.
Tirzepatide may reduce the efficacy of oral hormonal contraceptives. Use a non-oral barrier method of contraception for four (4) weeks after initiating tirzepatide and for four (4) weeks after each dose escalation.
Compounded medications carry additional risks including: variability in potency and sterility between batches, absence of FDA manufacturing oversight, lack of standardized excipient profiles, potential for contamination, and limited adverse event reporting infrastructure. As of July 2025, the FDA had received 605 adverse event reports linked to compounded semaglutide and 545 for compounded tirzepatide, many involving dosing errors where patients administered 5-20× their intended dose.
GLP-1 receptor agonists should NOT be used if you have: a personal or family history of medullary thyroid carcinoma (MTC) or MEN 2; a known hypersensitivity to semaglutide, tirzepatide, or any component of the formulation; a history of pancreatitis; current pregnancy, plans to become pregnant, or current breastfeeding.
Alternatives include: lifestyle modifications (diet and exercise), other FDA-approved weight management medications, bariatric surgery, or no treatment. Your prescriber can discuss which alternatives may be appropriate.
