Abstract
Introduction: Bariatric surgery is the most effective treatment modality for individuals with morbid obesity, providing significant and durable weight loss and comorbidity resolution. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide receptor agonists have shown promise as weight loss drugs, in addition to their use in the treatment of metabolic disorders. While multimodal weight management is the standard of care for individuals with morbid obesity, the benefit of antecedent GLP-1 therapy prior to bariatric surgery has not been well-studied. The objective of this study is to conduct a clinical trial testing the hypothesis that preoperative treatment with a dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonist enhances preoperative weight loss and decreases tissue inflammation, resulting in improved postoperative outcomes.
Materials and methods: We designed a randomized controlled trial (RCT) comparing preoperative treatment with tirzepatide versus standard medical care prior to minimally invasive bariatric surgery with a target enrollment of 50 patients randomized 1:1. For 3 mo preoperatively, the control arm will receive standard care in the form of dietary and lifestyle modification recommendations, whereas the treatment arm will receive weekly tirzepatide, in addition to standard care. Blood will be collected at enrollment through 12-mo postoperatively and analyzed for inflammatory and metabolic markers. Tissues (adipose, stomach, and liver) will be collected intraoperatively for transcriptome profiling and histological assessment.
Results: This is an ongoing trial with no reportable results.
Conclusion: Completion of this pilot RCT will provide data to support initiation of a multi-center RCT to determine therapeutic efficacy, and mechanisms of action, by which patients could benefit from preoperative treatment with tirzepatide.
Document Type
Article
Publication Date
2026
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.jss.2026.01.004
Funding Information
This project was funded by the Office of the Provost, the Vice President for Research (VPR), University of Kentucky and the College of Medicine Executive Clinical Expert Leadership (EXCEL) Research Initiative, Department of Surgery, Diabetes and Obesity Research Priority Area, and Barnstable Brown Diabetes Center at the University of Kentucky.
Repository Citation
Jain, Varun; McMullen, Colleen A.; Kimbrough, Joy I.; Rockich, Anna K.; Davenport, Daniel L.; Hawk, Gregory S.; Nikolajczyk, Barbara S.; Kern, Philip A.; Fisher, Simon J.; Steiner, Joshua P.; Inabnet, William B. III; and Starr, Marlene E., "Preoperative Glucagon-like Peptide-1 Therapy in Bariatric Surgery Patients with Morbid Obesity (PreMO): Rationale and Study Design for a Randomized Controlled Trial" (2026). Surgery Faculty Publications. 54.
https://uknowledge.uky.edu/surgery_facpub/54
Notes/Citation Information
0022-4804/$ — see front matter © 2026 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).