Renal Outcomes and Cardiorenal Mechanisms in Type 2 Diabetes: Highlights from the FLOW and ACHIEVE-4 Trials - report from EASD 2026

First, we did a proteomic analysis from the FLOW trial.

And just to remind you, FLOW was the one and only dedicated kidney outcomes trial with a GLP-1 receptor agonist, semaglutide, that showed remarkable benefits.

Twenty-four percent reduction in major kidney outcomes, including loss of function, kidney failure, major adverse cardiovascular events, and even mortality.

So this really has been a landmark trial, but we need to understand more about how it works.

Especially for endocrinologists, we get asked, "Is it weight? Is it glycemia?" No.

We did mediation analyses, and less than ten percent of the benefit on the kidney could be attributed to metabolic benefits.

So we're now looking toward direct effects on the kidney.

So in this analysis, we took blood for the proteomic analysis to see what proteins in the blood changed, and were they related to conventional markers.

So the long and short of it is that we looked at the change in the marker between baseline and twelve weeks, and then we said, "Did the change in the marker predict the kidney outcome?" We found that independent of eGFR, which is our main measure of kidney function, or urinary albumin, uh, that there were independent effects of proteins in certain, uh, pathways, metabolic, hemodynamic, fibrotic, and inflammatory pathways that were regulated in response to semaglutide.

Now, what should that mean for clinicians? Well, what we've shown is that independent of the markers you use to measure kidney function and damage, we're now seeing a signal that we are affecting mediators that cause kidney damage that come from different pathways.

W-Where does this take us in the future? It takes us really to precision medicine, using these markers to predict response and even to develop more targeted responses.

And also for those of you showing that GLP-1 receptor agonists, while very beneficial in metabolic parameters, appear to have direct effects on target organs that modify major mechanisms of damage.

So we're excited about this and where it will take us next in terms of therapeutic development.

First, we did a proteomic analysis from the FLOW trial.

And just to remind you, FLOW was the one and only dedicated kidney outcomes trial with a GLP-1 receptor agonist, semaglutide, that showed remarkable benefits.

Twenty-four percent reduction in major kidney outcomes, including loss of function, kidney failure, major adverse cardiovascular events, and even mortality.

So this really has been a landmark trial, but we need to understand more about how it works.

Especially for endocrinologists, we get asked, "Is it weight? Is it glycemia?" No.

We did mediation analyses, and less than ten percent of the benefit on the kidney could be attributed to metabolic benefits.

So we're now looking toward direct effects on the kidney.

So in this analysis, we took blood for the proteomic analysis to see what proteins in the blood changed, and were they related to conventional markers.

So the long and short of it is that we looked at the change in the marker between baseline and twelve weeks, and then we said, "Did the change in the marker predict the kidney outcome?" We found that independent of eGFR, which is our main measure of kidney function, or urinary albumin, uh, that there were independent effects of proteins in certain, uh, pathways, metabolic, hemodynamic, fibrotic, and inflammatory pathways that were regulated in response to semaglutide.

Now, what should that mean for clinicians? Well, what we've shown is that independent of the markers you use to measure kidney function and damage, we're now seeing a signal that we are affecting mediators that cause kidney damage that come from different pathways.

W-Where does this take us in the future? It takes us really to precision medicine, using these markers to predict response and even to develop more targeted responses.

And also for those of you showing that GLP-1 receptor agonists, while very beneficial in metabolic parameters, appear to have direct effects on target organs that modify major mechanisms of damage.

So we're excited about this and where it will take us next in terms of therapeutic development.