Compounded Semaglutide and Tirzepatide Products Use Unique Formulations but Efficacy and Safety Largely Unknown.
This study investigated compounded semaglutide and tirzepatide products being sold by compounding pharmacies following the resolution of the innovator drug shortage. Researchers conducted a Google-based search of compounding pharmacy websites between February and March 2025, identifying 33 unique compounded GLP-1 products. Two-thirds contained semaglutide and one-third contained tirzepatide. Nearly half of the products combined the active GLP-1 ingredient with additional agents such as cyanocobalamin, glycine, niacinamide, docusate, or ondansetron. Single-ingredient products were predominantly offered in sublingual (82%) or oral disintegrating tablet (ODT) (18%) formulations. The study found that the vast majority of products lacked transparency around beyond-use dating and storage conditions. The authors concluded there was little scientific justification for adding nutrients or docusate sodium to these formulations; while ondansetron co-formulation had a theoretical rationale, evidence for subcutaneous delivery was absent. Sublingual and ODT formats also lacked comparative evidence against FDA-approved oral tablets. A key limitation is that this was an observational web survey, not a clinical study, so no safety or efficacy data on patients were collected or analyzed.
Why this grade: This is a descriptive web-based survey of pharmacy product listings with no clinical data, patient outcomes, or controlled comparisons, making it insufficient to grade efficacy or safety in humans.
Background With the shortage of innovator semaglutide or tirzepatide products resolved, compounding pharmacies can only legally sell unique products. Unique products could have a different route of administration or dosing, or could include additional pharmaceutical ingredients. Objective To identify and characterize compounded semaglutide and tirzepatide products that differ from available FDA-approved products. Methods We searched compounding sites between February 3, 2025, and March 20, 2025, using key terms ["compounded semaglutide," "compounded tirzepatide," and "compounded GLP-1s"] on Google looking for products with a strength, route of administration, and/or formulation that differed from commercially available products. Results We identified 33 unique semaglutide and/or tirzepatide products. Two-thirds contained semaglutide, and one-third contained tirzepatide. Forty-eight percent of products contained either semaglutide or tirzepatide with some combination of cyanocobalamin, glycine, niacinamide, docusate, or ondansetron. The 17 single active ingredient products were provided in sublingual (82%) or oral disintegrating tablet (ODT) (18%) formulations. Only 18% of included compounded products reported information about beyond use date and preferred storage conditions. Twenty-eight percent reported preferred storage conditions. Conclusion and relevance We found little justification for adding nutrients or docusate sodium to combination subcutaneous semaglutide or tirzepatide products. There is a rationale for adding ondansetron, but evidence for subcutaneous administration is lacking. There is a rationale for fashioning sublingual or ODT formulations, but whether these formulations offer advantages over innovator oral tablets has not been determined. The popularity of these products as an alternative to FDA-approved medications is concerning, given the lack of evidence for safety and efficacy.
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