Glycaemic and non-glycaemic efficacy of once-weekly GLP-1 receptor agonists in people with type 2 diabetes

Abstract

What is known and objective: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may confer a range of benefits for people with type 2 diabetes (T2D), which is reflected through their position within diabetes treatment guidelines. The objective of this narrative review is to explore the efficacy data of once-weekly (QW) GLP-1 RAs in terms of glycaemic control, body weight reduction, cardiovascular (CV) outcomes and potential renal protective effects to assist pharmacists and other healthcare professionals (HCPs) in treatment discussions with patients.

Methods: This a narrative review focused on 31 clinical trials involving the Phase 3 clinical programmes of the QW GLP-1 RAs dulaglutide, exenatide extended-release (ER) and semaglutide subcutaneous (s.c.).

Results and discussion: The clinical trials were divided by their comparator arms and examined for trends. All QW GLP-1 RAs were superior to placebo for reductions in glycated haemoglobin (HbA_1c ) and body weight. Data regarding QW GLP-1 RAs versus metformin were limited, likely due to metformin's use as the first-line pharmacologic for T2D. In the robust head-to-head trials of QW versus QW GLP-1 RAs, semaglutide s.c. was superior to both dulaglutide and exenatide ER regarding HbA_1c and body weight; however, QW versus once-daily GLP-1 RA trials had mixed results depending on the comparators. Finally, in QW GLP-1 RA versus insulin trials, all QW GLP-1 RAs were as effective as insulin, particularly when hypoglycaemia and body weight were also considered. CV outcome trials demonstrated benefits in major adverse CV events and renal outcomes for semaglutide and dulaglutide.

What is new and conclusion: This review collates recently published data and previously published Phase 3 results to allow pharmacists and other HCPs to understand all of the efficacy data available and the corresponding impact on treatment guidelines. QW GLP-1 RAs are emerging as important therapeutic options for people with T2D as they offer a spectrum of benefits extending beyond glycaemic control, but it is important to be aware of their efficacy differences when prescribing and discussing them with patients.

Keywords: efficacy; glucagon-like peptide-1 receptor agonist; glycaemic control; type 2 diabetes; weight loss.