Over a relatively short period,
obesity and
type 2 diabetes have come to represent a large medical and economic burden to global societies. The epidemic rise in the prevalence of
obesity has metabolic consequences and is paralleled by an increased occurrence of other diseases, such as diabetes,
cancer and cardiovascular complications. Together,
obesity and
type 2 diabetes constitute one of the more preventable causes of premature death and the identification of novel, safe and effective
anti-obesity drugs is of utmost importance. Pharmacological attempts to treat
obesity have had limited success, with notable adverse effects, rendering
bariatric surgery as the only current
therapy for substantially improving
body weight. Novel unimolecular, multifunctional
peptides have emerged as one of the most promising medicinal approaches to enhance metabolic efficacy and restore normal body weight. In this review, we will mainly focus on the discovery and translational relevance of dual agonists that pharmacologically function at the receptors for
glucagon and
glucagon-like peptide-1. Such
peptides have advanced to clinical evaluation and inspired the pursuit of multiple related approaches to achieving
polypharmacy within single molecules.