Recent updates on GLP-1 agonists: Current advancements & challenges

Glucagon-like peptide (GLP)-1 is an incretin hormone exhibiting several pharmacological actions such as neuroprotection, increased cognitive function, cardio-protection, decreased hypertension, suppression of acid secretion, increase in lyposis, and protection from inflammation. The most potent actions are glucose-dependent insulinotropic and glucagonostatic actions, stimulation of β-cell proliferation, enhanced insulin secretion and reduced weight gain in patients with type-2 diabetes pertaining to blood glucose control. Despite all these actions, its short half-life (around 2∼min) and degradation by a dipeptidyl peptidase-4 enzyme (DPP-4) limits the therapeutic utility of GLP1. In this review, we have discussed DPP IV-resistant analogs of GLP-1 currently present in clinical trials such as Exenatide, Liraglutide, Semaglutide, Efpeglenatide, Exenatide ER, Ittca 650 (Intarcia), Dulaglutide, Albiglutide, and Lixisenatide. Moreover, we have also discussed in detail the pharmacology, signaling mechanisms, and pharmacokinetic properties (Cmax, Tmax, T1/2, Vd, and Bioavailability) of DPP IV-resistant analogs of (GLP-1). Interestingly, GLP-1 agonist drugs have shown better potential to treat type-2 diabetes mellitus (T2DM) as compared to currently used drugs in clinics without causing the side effects of hypoglycemia and weight gain.