The applicability of stable gut
hormones for the treatment of
obesity-related diabetes is now undisputable. This is based predominantly on prominent and sustained
glucose-lowering actions, plus evidence that these
peptides can augment insulin secretion and pancreatic islet function over time. This review highlights the therapeutic potential of
glucagon-like peptide-1 (GLP-1),
glucose-dependent insulinotropic
polypeptide (GIP),
oxyntomodulin (OXM) and
cholecystokinin (CCK) for
obesity-related diabetes. Stable
GLP-1 mimetics have already been successfully adopted into the diabetic clinic, whereas GIP, CCK and OXM molecules offer promise as potential new classes of
antidiabetic drugs. Moreover, recent studies have shown improved
therapeutic effects following simultaneous modulation of multiple receptor signalling pathways by combination
therapy or use of dual/triple agonist
peptides. However, timing and composition of
injections may be important to permit interludes of beta-cell rest. The review also addresses the possible perils of
incretin based drugs for treatment of
prediabetes. Finally, the unanticipated utility of stable gut
peptides as effective treatments for complications of diabetes, bone
disorders, cognitive impairment and cardiovascular dysfunction is considered.