A review of GLP-1 receptor agonists in type 2 diabetes: A focus on the mechanism of action of once-weekly agents

Abstract

What is known and objective: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are one of the preferred approved treatment options for people with type 2 diabetes (T2D) and inadequate glycaemic control. The objective of this review is to provide a general clinical overview of the similarities and differences in the mechanisms of action (MoA) of the once-weekly GLP-1 RA class of medications, highlighting the role of pharmacists in providing optimal medication management, education and care for people with diabetes.

Methods: This is a narrative review of the published literature regarding the MoA of the currently available once-weekly GLP-1 RAs in T2D.

Results and discussion: GLP-1 RAs have an established efficacy and safety profile. Their benefits derive from their blood glucose-lowering effects, which include pancreatic beta-cell-mediated glucose-dependent insulin secretion and suppressed glucagon release, and their ability to slow gastric emptying and promote satiety. GLP-1 RAs may also exert beneficial effects on multiple organ systems in which GLP-1 receptors are present, including the cardiovascular and renal systems. Differences between individual GLP-1 RAs with regard to their molecular size, structure and duration of action (short or longer acting) have led to differing pharmacodynamics and clinical effects such as degree of glycaemic control, weight loss abilities, cardiovascular effects and tolerability profiles.

What is new and conclusion: From the literature, this appears to be the first review of the evidence base supporting the MoA of once-weekly GLP-1 RAs in T2D aimed at pharmacists, with a particular emphasis on the expanding role of pharmacists in team-based diabetes management. As a class, GLP-1 RAs are an effective treatment option for people with T2D, shown to achieve multi-factorial clinical benefits. The results suggest that when selecting or advising about treatments, pharmacists should consider how the different once-weekly GLP-1 RAs and their MoA affect clinical outcomes in order to ensure optimal treatment for individuals.

Keywords: Type 2 diabetes; cardiovascular diseases; diabetes mellitus; dulaglutide; exenatide; glucagon-like peptide-1 receptor agonist; glycaemic control; mechanism of action; semaglutide.