Use of Adjuvant Anti-Obesity Medication to Enhance Surgical Weight Loss

Vanderbilt University Medical Center, Nashville TN

Investigators

Abstract

Project Summary/Abstract Obesity affects nearly half of the U.S. population, impacting health outcomes including diabetes, cardiovascular risk, longevity, and quality of life. While bariatric surgery such as gastric bypass stands as the most effective intervention, 65% of individuals experience persistent obesity when undergoing surgical weight loss alone. Given the wide-ranging impact of obesity on health outcomes, a critical need exists to explore the efficacy of adjuvant weight loss therapies after gastric bypass surgery. Tirzepatide (TRZ), a type of glucagon- like peptide-1 receptor agonist, shows remarkable effectiveness in medical obesity with 25% weight loss after sustained therapy. However, nearly two-thirds of patients taking medications like TRZ have mild to moderate gastrointestinal (GI) symptoms, including nausea, vomiting, and abdominal pain. These medication side-effects could be a consequence of gastroparesis via vagal stimulation of the stomach, and may represent a major driver of weight loss. Limited data exist regarding use of these newer agents, such as TRZ, in patients who have undergone gastric bypass, which disrupts vagal nerves responsible for managing food transit and gastric emptying. This is a major and timely scientific gap in understanding whether gastric bypass surgery might mitigate these GI symptoms while allowing for enhanced weight loss with adjuvant TRZ use in the post- operative period. We propose a pilot, phase II, open-label trial enrolling patients twelve months after gastric bypass with a nadir Body Mass Index ≥ 30 kg/m2. Study subjects will be randomized to either 24 weeks of TRZ or post-surgery standard of care. Our proposal consists of two aims. First, we will determine the impact of adjuvant TRZ administration on weight, total fat mass, and lean body mass in patients with a history of gastric bypass (Aim 1). Second, we aim to investigate the frequency and severity of GI discomfort associated with TRZ utilizing a validated patient reported outcome questionnaire, and we will investigate the impact of TRZ on GI motility in patients with prior Gastric Bypass (Aim 2). This proposal delineates Dr. Samuels’s career development plan, "Use of Adjuvant Anti-Obesity Medication to Enhance Surgical Weight Loss." With a robust background in caring for over 500 bariatric surgery patients, Dr. Samuels’s time on this K23 will be dedicated to developing him as a leader in clinical trials investigating multimodal treatment strategies for obesity. This career development award is critical to Dr. Samuels’s efforts to become an independently funded investigator following the completion of Dr. Samuels’s career development plan. Dr. Samuels’s mentorship team carries expertise in surgical clinical trials (Mayur B. Patel), anti-obesity pharmacotherapy trials (Kevin D. Niswender), clinical trials investigating behavioral interventions for obesity (Luke Funk), large database comparative effectiveness studies (Christianne Roumie), and pragmatic, electronic records-based clinical trials (Wesley Self). This award will position Dr. Samuels to become a leader in obesity-related clinical trials.