Tirzepatide

Tirzepatide is a once-weekly injectable dual agonist of GLP-1 and GIP receptors, FDA approved for type 2 diabetes (Mounjaro) and weight management (Zepbound). Clinical trials demonstrate weight reductions exceeding those seen with semaglutide in head-to-head comparisons. Compounded formulations were widely offered by telehealth and functional medicine providers while tirzepatide was on the FDA drug shortage list; that pathway has since closed (see access and regulatory status below). It represents the current clinical benchmark for pharmacological weight management. Mechanism of action: Tirzepatide activates two incretin receptors simultaneously — the glucagon-like peptide-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor. GLP-1 activation suppresses appetite, slows gastric emptying, and potentiates insulin secretion; GIP activation independently stimulates insulin release and may reduce some of the GI side effects associated with pure GLP-1 agonism. The dual mechanism produces greater appetite suppression and metabolic improvement than either receptor pathway alone, which accounts for the superior weight reduction seen in clinical trials relative to semaglutide. Clinical evidence: The SURMOUNT trial program established tirzepatide's weight reduction profile. SURMOUNT-1 (2022) found a mean weight reduction of 22.5% over 72 weeks at the highest dose (15mg/week) vs 2.4% with placebo — the largest mean weight reduction reported for any approved pharmacological intervention at that time. SURMOUNT-5 (2024) was a direct head-to-head comparison with semaglutide 2.4mg: tirzepatide 10mg and 15mg produced significantly greater weight reductions (20.2% vs 13.7% for semaglutide). The SURPASS trials established cardiometabolic and glycaemic benefits in T2D contexts. Tirzepatide vs semaglutide: Tirzepatide's dual GIP+GLP-1 mechanism produces greater mean weight reductions in trials but also a distinct side effect profile. GI tolerability may be slightly better than pure GLP-1 agonism for some users due to the GIP component, though nausea and gastrointestinal symptoms remain the most common adverse effects. Semaglutide has a larger body of long-term safety data; tirzepatide has superior head-to-head efficacy data. Prescribers select between them based on clinical context, cost, access, and patient response history. Access and regulatory status: Tirzepatide requires a prescription from a licensed provider. Branded formulations (Mounjaro, Zepbound) are available at licensed pharmacies. Compounded tirzepatide was permitted only while tirzepatide 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 18 February 2025 for state-licensed pharmacies and physicians compounding under section 503A of the FD&C Act, and until 19 March 2025 for outsourcing facilities under section 503B; the FDA has since confirmed that those periods have ended. As of the FDA's 1 April 2026 statement, tirzepatide does not appear on the 503B bulks list or on the FDA drug shortage list, so compounded tirzepatide 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. Providers offering tirzepatide-based programs are indexed in the PeptideBase directory.