A Pilot Study Examining the Effects of GLP-1 Receptor Blockade Using Exendin-(9,39) on Gastric Emptying and Caloric Intake in Subjects with and without Bariatric Surgery

Background: Obesity causes significant morbidity and mortality and continues to be a significant public health concern. Unfortunately, lifestyle modification and pharmacotherapy do not produce durable results. This has led to bariatric surgical procedures playing an increasingly prominent role in the management of medically complicated obesity. Roux-en-Y gastric bypass and sleeve gastrectomy are the most commonly performed bariatric surgeries in North America and produce mechanical restriction with accelerated gastrointestinal transit accompanied by increased postprandial secretion of glucagon-like peptide-1 (GLP-1). GLP-1 is a gastrointestinal hormone that delays gastric emptying and causes satiety and weight loss. This raises the possibility that the postprandial rise in GLP-1 might affect feeding behavior over and above the mechanical restriction produced by bariatric surgery. Methods: We, therefore, sought to determine the effects of GLP-1 receptor blockade using exendin-9,39 - a competitive antagonist of the actions of GLP-1 at its receptor - on caloric intake and gastrointestinal transit in subjects after sleeve gastrectomy and after Roux-en-Y gastric bypass compared with weight-matched controls. Results: GLP-1 receptor blockade did not alter caloric intake in people after bariatric surgery. However, caloric intake was decreased in age-, weight- and sex-matched control subjects, and the mechanisms require further study. Conclusions: Given the known effects of GLP-1 on gastric accommodation, future studies should ascertain effects of GLP-1 receptor blockade on gastric accommodation, which might be a useful and novel strategy to decrease caloric intake in humans with an intact upper gastrointestinal tract. The Clinical Trial Resigtration number is NCT02779075.