Glucagon-like peptide 1 (GLP-1) receptor agonists are currently widely used in the treatment of Type 2 Diabetes Mellitus, and are being investigated as a potential anti-obesity therapy thereby increasing the target group of patients. However, safety concerns have been raised from reports suggesting a link between GLP-1 based treatments, high pancreatic ductal replication and increased amylase secretion from acinar cells, potentially increasing the risk of pancreatitis. This has triggered a number of in vivo chronic studies with conflicting results. However little is known about the acute effect of GLP-1 on functions of the exocrine pancreas. Amylase secretion in vivo and in vitro was assessed in the four main peptides intended to be used as obesity therapeutics. . To evaluate the acute exocrine effect in vivo, male Wistar rats (350-500g) were anaesthetised using isoflurane (1.5-2%), and an intravenous bolus injection of 30 nmol GLP-1 (7−36), glucagon, oxyntomodulin or exendin-4, alone and in combination with cholecystokinin (CCK), was administered through the femoral vein (n= 3- 5). Plasma levels of amylase were determined from right jugular vein sampling performed at 50 mins post injection. Results were compared to baseline pre-treatment plasma and presented as means ± SEM by ANOVA. Rat pancreatic acinar cells (AR42J) were treated with ascending concentrations of the peptides and CCK, and medium was assayed to evaluate amylase secretion. Plasma amylase concentration did not increase post peptide injection in vivo, compared to vehicle and CCK. Of note, when oxyntomodulin was co administered with CCK, it suppressed amylase secretion by 4 μmol/ml ±0.3, compared to CCK alone. Nonetheless, in vitro amylase secretion post oxyntomodulin/ CCK cellular treatment was not significantly suppressed, when compared to CCK. These results suggest that GLP-1, glucagon and exendin-4 do not have an acute effect on exocrine pancreatic function, while oxyntomodulin appears to suppress digestive enzyme secretion, yet not directly through down regulation of amylase release. Thus, it could be the safest choice for an obesity treatment, with regard to pancreatitis.