Post-pancreatitis diabetes mellitus: investigational drugs in preclinical and clinical development and therapeutic implications

Abstract

Introduction The need for new drugs for diabetes is obvious. Albeit type 2 diabetes is the most common type of diabetes, it is fundamentally a disease of exclusion. Post-pancreatitis diabetes mellitus is one of the most common types of secondary diabetes. The pharmaceutical armamentarium in the field of diabetology can be broadened if the design of novel drugs is informed by pathogenetic insights from studies on post-pancreatitis diabetes mellitus. Areas covered The article provides an overview of preclinical and clinical studies of compounds selectively antagonising the gastric inhibitory peptide receptor, simultaneously stimulating both the glucagon-like peptide-1 and glucagon receptors, and activating ketogenesis. Expert opinion The current pharmacotherapy for post-pancreatitis diabetes mellitus is relatively ineffective. This type of diabetes represents a unique platform for rigorous, efficient, and practical search for glucose-lowering therapeutic candidates. Various methods of gastric inhibitory peptide receptor (expressed in the pancreas) antagonism have undergone extensive preclinical testing in diabetes, with promising compounds being trialled in man. Molecular mimicry with oxyntomodulin ─ an extra-pancreatic hormone homologous with pancreatic hormone glucagon and involved in the regulation of exocrine pancreatic function ─ could be harnessed. The emerging findings of a salutary effect of ketosis mimetics in people with prediabetes or obesity set the stage for a novel approach to preventing diabetes.