A role for exogenous GLP-1 in the management of postprandial hypoglycaemia after Roux-en-Y gastric bypass?

Roux-en-Y gastric bypass (RYGB) is one of the most common and successful bariatric surgeries. However, more than half of RYGB-operated individuals may suffer from post-bariatric hypoglycaemia (PBH) characterised by traditional hypoglycaemic symptoms occurring 1 to 4 hours after meal intake. The mechanisms underlying PBH most likely relate to accelerated delivery of nutrients to the small intestine resulting in unretarded nutrient absorption, large elevations in postprandial plasma glucose concentrations (constituting a potent insulin secretory stimulus), and grossly elevated postprandial plasma levels of the insulinotropic gut-derived hormone glucagon-like peptide 1 (GLP-1) potentiating glucose-stimulated insulin secretion. Based on previous findings that circulating GLP-1 concentrations increased by similar to 100% during insulin-induced hypoglycaemia before but not after RYGB, Almby et al. explored whether exogenous GLP-1 may protect against PBH. They performed hyperinsulinaemic hypoglycaemic clamps with concomitant infusion of the GLP-1 analogue exenatide and saline, respectively, in individuals who had undergone RYGB surgery. Infusion with exenatide during hypoglycaemia had no plasma glucose-raising effects, did not increase the counterregulatory glucagon response, and did not affect symptom scores. In the present commentary, potentially important implications derived from the study by Almby et al. published in the August issue of EJE, are discussed in the light of previous observations on GLP-1 receptor agonist treatment in PBH. While the findings by Almby et al. do not provide a solution for patients with PBH, they contribute to the knowledge base needed to address the growing problem of PBH.