GLP-1: The Oracle for Gastric Bypass?

Abstract

Despite enormous efforts to find effective pharmacological targets, bariatric surgery is still the most effective treatment for morbid obesity. Beyond weight loss, this procedure often results in remarkable improvements in type 2 diabetes (T2D). However, several clinical trials have shown that between 22 and 28% of patients with T2D did not experience improvements in their diabetes after surgery (1). Personalized medicine seeks to identify the best possible therapeutic outcome with minimal adverse events. However, it requires an understanding of the molecular underpinnings of disease as well as signaling pathways triggered by both pharmacological and surgical treatments that predict an individual’s likelihood of responding favorably to treatment. Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is released into the bloodstream postprandially from the ileum and colon. Among its multiple biological actions (2), GLP-1 stimulates insulin secretion in a glucose-dependent manner (3,4) and decreases appetite (5). GLP-1–based T2D therapies are now commonly used in combination with other drugs with the added weight-loss effect broadening its therapeutic application in human obesity (6,7). Since bariatric surgery causes weight loss and T2D remission with enhanced postprandial GLP-1 secretion, the role of GLP-1 as a mediator of surgery-associated benefits has been investigated (8,9). However, to date, this hypothesis remains inconclusive because mice lacking GLP-1 receptors (GLP-1Rs) responded similarly to controls after vertical sleeve gastrectomy (10). In this issue, Habegger et al. …