A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives

Type 2 diabetes (T2D), which has currently become a global pandemic, is ametabolic disease largely characterised by impaired insulin secretion and action. Significantprogress has been made in understanding T2D aetiology and pathogenesis, which is discussedin this review. Extrapancreatic pathology is also summarised, which demonstrates the highlymultifactorial nature of T2D. Glucagon-like peptide (GLP)-1 is an incretin hormone responsiblefor augmenting insulin secretion from pancreatic beta-cells during the postprandialperiod. Given that native GLP-1 has a very short half-life, GLP-1 mimetics with a muchlonger half-life have been developed, which are currently an effective treatment option for T2Dby enhancing insulin secretion in patients. Interestingly, there is continual emerging evidencethat these therapies alleviate some of the post-diagnosis complications of T2D. Additionally,these therapies have been shown to induce weight loss in patients, suggesting they could be analternative to bariatric surgery, a procedure associated with numerous complications. CurrentGLP-1-based therapies all act as orthosteric agonists for the GLP-1 receptor (GLP-1R).Interestingly, it has emerged that GLP-1R also has allosteric binding sites and agonists havebeen developed for these sites to test their therapeutic potential. Recent studies have alsodemonstrated the potential of bi- and tri-agonists, which target multiple hormonal receptorsincluding GLP-1R, to more effectively treat T2D. Improved understanding of T2D aetiology/pathogenesis, coupled with the further elucidation of both GLP-1 activity/targets and GLP-1Rmechanisms of activation via different agonists, will likely provide better insight into thetherapeutic potential of GLP-1-based therapies to treat T2D