Preoperative Glucagon-like Peptide-1 Therapy in Bariatric Surgery Patients With Morbid Obesity (PreMO): Rationale and...

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.

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.

This is an ongoing trial with no reportable results.

Completion of this pilot RCT will provide data to support initiation of a multicenter RCT to determine therapeutic efficacy, and mechanisms of action, by which patients could benefit from preoperative treatment with tirzepatide.