A review of GLP-1 receptor agonists: Evolution and advancement, through the lens of randomised controlled trials

Aims: To review the evolution and advancement of GLP-1 receptor agonist (GLP-1RA) therapy, through the lens of randomised controlled trials, from differentiating characteristics, efficacy, safety, tolerability, and cardiovascular outcomes, to evidence gaps and next steps. Methods: Clinical review of published phase 3 or later RCT data studying efficacy, safety, and outcomes of approved GLP-1 RA therapies. Results: Through a wealth of studies, including both placebo-controlled and active-controlled studies, GLP-1 RAs have demonstrated high glycemic efficacy and ability to facilitate weight loss, with minimal risk of hypoglycemia, potential to restore beta cell function, and evidence for improved cardiovascular outcomes in those at risk. Conclusions: Over a decade of clinical studies have established the unique contributions of GLP-1 RAs in the treatment of diabetes. Individual differences between the different GLP-1 RAs, in delivery, pharmacokinetic and clinical effects, exist, allowing for tailored approaches to clinical care. The strength of evidence generated through RCTs, both short-term and long-term studies, will continue to evolve and inform our current paradigms in diabetes care.