Combinations of antibodies with peptide hormones are also offering promising effects. These include dual agonists at GLP-1 and gastric inhibitory polypeptide (GIP) receptors, dual agonists at GLP-1 and glucagon receptors, and triple agonists at GLP-1, GIP and glucagon receptors. Chimeric molecules with agonistic effects at two or more receptors are also advancing in clinical studies. Other mixtures and hybrids of two or more complementary peptides are receiving investigation as potential therapies for the treatment of type 2 diabetes, mostly based on analogues of gastro-intestinal and adipose-derived hormones.
Examples of stable mixtures of peptides with different physicochemical properties are the fixed-ratio combinations of insulin with a glucagon-like peptide-1 receptor agonist (GLP-1RA), which improve glucose-lowering efficacy while reducing insulin dose, avoiding weight gain and lowering risk of hypoglycaemia compared with insulin alone. Advances in protein therapeutics to simultaneously target more than one cell surface receptor using mixtures of peptides, hybrid peptides or chimeric peptides in a single administration offer new opportunities to address a diversity of medication needs.
The management of diabetes involves attention to multiple pathogenic factors that affect the control of glycaemia, weight, cardio-renal risk and associated morbidities. New avenues in protein drugs for diabetes: targeting more than one receptor
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