SAT-635 Results of a Preclinical Pilot Study Evaluating 24-Hour Subcutaneous Infusion of the GLP-1 Analogue Liraglutide Delivered via the H-Patch Wearable Device

Abstract

Nonalcoholic fatty liver disease (NAFLD) affects an estimated 30% of Americans, is the most common cause of chronic liver disease in the US, and a leading cause of liver-related morbidity/mortality worldwide1. Currently, there are no FDA-approved drugs specifically tailored to NAFLD or its big brother, non-alcoholic steatohepatitis (NASH). Glucagon-like peptide 1 (GLP-1) is an incretin peptide hormone, secreted in the distal ileum and proximal colon by L cells. Besides stimulating the pancreas to cause beta cell proliferation and enhance insulin biosynthesis, GLP-1 interacts with receptors in other parts of the GI tract, lung, kidney and CNS. Thus, GLP-1’s metabolic functions include delayed gastric emptying, appetite suppression, enhanced liver glucose uptake, peripheral insulin sensitivity, as well as glucose-dependent insulin secretion while inhibiting the release of glucagon from α-cells. While GLP-1 receptor agonists such as exenatide and liraglutide have been approved for type 2 diabetes, a meta-analysis of several studies has shown promise in patients with NASH. Effects including decreased serum ALT levels, improvement in hepatic fat content and fibrosis, and weight loss making GLP-1 therapeutics potentially attractive for use in patients with NASH and metabolic syndrome2-5. While subcutaneous injection is an avenue for administration, continuous infusion offers many benefits for native GLP-1 and GLP-1 analogues. We investigated the pharmacokinetics (PK) of a GLP-1 analogue (liraglutide) delivered over a single 24h period using the wearable h-Patch™ subcutaneous infusion device in dogs. Liraglutide (1800ug) was infused at a static rate over 24h delivered with PK evaluated at time points to 72h from the start of infusion. Liraglutide levels were detectable in blood detected within 30m of the beginning of infusion, peaked above the upper level of quantitation of the LC/MS/MS analysis (316ng/ml upper level of quantitation), and gradually decreased with quantifiable levels still detected 48h after completion of h-Patch™ infusion. The h-Patch™ provides a simple all-in-one delivery device with no exposed needle, no programming or infusion set required, additionally it can be configured to deliver two payload in separate reservoirs offering the potential option of an insulin/GLP-1 infusion combination. These preliminary encouraging results of liraglutide infusion via the h-Patch warrant further investigation in a variety of indications including diabetes, NASH, and obesity as a monotherapy and in combination with other complementary therapeutics. 1. Liver Int. 2017; 37(S1):97-103. 2. Lancet. 2016; 387(10019):679-690. 3. J Gastroenterol Hepatol. 2016; 31(1):23-31. 4. Clin Ther. 2007; 29(1):139-153. 5. Aliment Pharmacol Ther. 2013; 37(2):234-242.