The SELECT and FLOW trials investigate semaglutide's cardiovascular benefits in obese people without diabetes and renal outcomes in diabetic kidney disease, potentially expanding GLP-1 therapy beyond diabetes.
2 landmark trialsSELECT (cardiovascular in obesity) and FLOW (renal in T2D) testing semaglutide beyond diabetes
What the researchers found
The SELECT trial is the first pharmacotherapy study in obesity powered for cardiovascular superiority in people without T2D, while FLOW is the first dedicated study of GLP-1 receptor analog effects on renal outcomes in diabetic kidney disease.
Why it matters
If semaglutide reduces cardiovascular events in obese people without diabetes and protects kidneys in diabetic kidney disease, it could transform treatment paradigms for two of the world's most common and deadly conditions.
The numbers in context
SUSTAIN-6: 26% reduction in MACE; PIONEER 6: confirmed CV safety of oral semaglutide.
How the study worked
Review of prior GLP-1 analog cardiovascular outcome trials and detailed discussion of the design and potential impact of the ongoing SELECT and FLOW semaglutide studies.
Who was studied
Adults with type 2 diabetes and cardiovascular risk
What this study cannot tell us
Written before trial results were available, so conclusions are speculative. Focused on semaglutide specifically and may not generalize to all GLP-1 analogs. Long-term safety of GLP-1 agonists in non-diabetic populations was still being established.
How to read the evidence
Review of trial designs with reference to prior CVOT data. Prospective trial results were not yet available when published.
When this study was published
Published in 2020, before SELECT and FLOW trial results. SELECT has since reported positive cardiovascular outcomes; FLOW showed kidney benefits. This review correctly anticipated the significance of both.
The bigger picture
This 2020 review anticipated what has since become reality: GLP-1 agonists like semaglutide have demonstrated cardiovascular and renal benefits beyond their metabolic effects. The SELECT trial later showed a 20% reduction in major cardiovascular events, validating the hypothesis discussed in this paper.
Questions still open
- Will cardiovascular benefits of semaglutide in obese non-diabetic populations lead to broader prescribing guidelines?
- How do semaglutide's renal protective effects compare to established nephroprotective drugs like SGLT2 inhibitors?
- What mechanisms beyond weight loss explain semaglutide's cardiovascular and renal benefits?
Common questions
What is the SELECT trial?
Why study semaglutide for kidney disease?
Read the original research
Semaglutide: Charting New Horizons in GLP-1 Analogue Outcome Studies.
Diabetes therapy : research, treatment and education of diabetes and related disorders, 11(10), 2221-2235
Citation
Williams, David M; Evans, Marc. (2020). Semaglutide: Charting New Horizons in GLP-1 Analogue Outcome Studies.. Diabetes therapy : research, treatment and education of diabetes and related disorders, 11(10), 2221-2235. https://doi.org/10.1007/s13300-020-00917-8