GLP-1 Receptor Agonists Post-Bariatric Surgery (GRABS) Pilot Trial

Obesity affects nearly half of the U.S. population, impacting health outcomes includingdiabetes, cardiovascular risk, longevity, and quality of life. While bariatric surgerysuch as gastric bypass stands as the most effective intervention, 65% of individualsexperience persistent obesity when undergoing surgical weight loss alone. Given thewide‐ranging impact of obesity on health outcomes, a critical need exists to explore theefficacy of adjuvant weight loss therapies after gastric bypass surgery. Tirzepatide(TRZ), a type of glucagon‐like peptide‐1 receptor agonist, shows remarkable effectivenessin medical obesity with 25% weight loss after sustained therapy. However, nearlytwo‐thirds of patients taking medications like TRZ have mild to moderate gastrointestinal(GI) symptoms, including nausea, vomiting, and abdominal pain. These medicationside‐effects could be a consequence of gastroparesis via vagal stimulation of thestomach, and may represent a major driver of weight loss. Limited data exist regardinguse 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 surgerymight mitigate these GI symptoms while allowing for enhanced weight loss with adjuvantTRZ use in the post‐operative period. The investigators propose a pilot, phase II,open‐label trial enrolling patients twelve months after gastric bypass with a nadir BodyMass Index ≥ 30 kg/m2. Study subjects will be randomized to either 24 weeks of TRZ orpost‐surgery standard of care. Subjects randomized to the standard of care arm willcrossover to receive the intervention drug after 24 weeks of observation. Our proposalconsists of two aims. First, the investigators will determine the impact of adjuvant TRZadministration on weight, total fat mass, and lean body mass in patients with a historyof gastric bypass (Aim 1). Second, the investigators aim to investigate the frequency andseverity of GI discomfort associated with TRZ utilizing a validated patient reportedoutcome questionnaire, and they will investigate the impact of TRZ on GI motility inpatients with prior Gastric Bypass (Aim 2).