Semaglutide: Charting New Horizons in GLP-1 Analogue Outcome Studies

The growing epidemic of obesity and diabetes represents a growing health emergency, exemplified by a marked increase in cardiovascular and renal disease. As such, healthcare systems are increasingly focussing on therapeutic approaches to address these challenges. Cardiovascular outcome trials (CVOTs) evaluating glucagon-like peptide-1 (GLP-1) analogues have previously observed significant improvements in major adverse cardiac events in people with type 2 diabetes (T2D). However, their impact in obese people without T2D is unknown. The SELECT study is the first pharmacotherapy study in obesity powered for cardiovascular superiority and investigates the impact of semaglutide on cardiovascular disease outcomes in overweight and obese people without T2D. The results of this study will potentially redefine obesity management, especially as secondary outcomes of the study will include evaluation of health-related quality of life and incident diabetes rates. In another potentially evolutionary therapeutic step for the incretin class of therapeutic agents, the FLOW study is the first dedicated study to investigate the effects of GLP-1 receptor analogues on renal and cardiovascular outcomes in people with renal impairment and T2D. Post-hoc analyses of GLP-1 analogue CVOTs have demonstrated reduced adverse renal outcomes associated with their use. In this review we discuss the known impact of GLP-1 analogues on cardiovascular, weight and renal outcomes in previous CVOTs. We further discuss the importance of the ongoing SELECT and FLOW studies on shifting the paradigm of obesity pharmacotherapy and in adding to our understanding of renal disease management in people with T2D.