"Hi, I'm Professor Will Herrington. I'm a nephrologist from the renal studies group at the University of Oxford. And in the ERA I'll be presenting an individual patient level data meta analysis on chronic kidneys outcomes using a drug called empagliflozin.

We've got several large trials of SGLT2 inhibitors, but we've still got some uncertainty among certain subgroups of patients that are progressing slowly, particularly those without diabetes and low levels of albuminuria. And we were also very interested to know whether or not the acute dip in eGFR, on initiation of such therapy might modify treatment effects.

Okay. Well, it's quite a complicated analysis because we have individual patient level data and that enables us to explore subgroups in much more detail than has been previously possible. And the first subgroups we were really interested in were people with diabetes and without diabetes and then with different levels of albinuria. And we found that using an outcome called chronic EGFR decline, we reduced the rate across all four large empagliflozin trials. That's the EMPA KIDNEY, the two EMPEROR trials, and the EMPA REG outcome trial. We reduced it by about 2/3.

We found the effect was slightly larger in people with diabetes than those without diabetes. In people with diabetes, the rate of decline was reduced by 75%, 3/4 reduced to about 2/5. In people without diabetes, we found a very interesting, and reverse trend where we saw larger effects in people with low levels of albuminuria, but that perhaps looks to be explained entirely by different proportions of people with diabetes. So in actual fact, if you don't have diabetes, irrespective of your level of albuminuria, you still slow progression by about 40%. And if you do have diabetes, irrespective of the level of albuminuria, you still have a benefit. And in fact it might be slightly larger in people with the lowest level of the A1 levels of albuminuria.

Okay, well, the key take home message here really is that neither diabetes nor levels of albuminuria should really be the main deciding factor for whether or not you treat someone with an SGLT2 inhibitor. The guidelines can be simplified based on these findings because it seems to be that people with CKD benefit and irrespective of those characteristics, not necessarily specific patient populations, because the trials, we're very lucky. Have studied very wide ranges of people, people with heart failure, people with cardiovascular disease, people with a broad range of type 3 kidney disease.

But I'd really like to see these analyses redone with different SGLT2 inhibitors and incorporating different outcomes. We really want to see whether or not these benefits we see on kidney disease progression are also seen in, hospitalisation, benefits in acute kidney injury benefits. And, the other benefits we see in terms of cardiovascular risk in this patient population. This study was just in people taking empagliflozin or placebo. I'd love to see it tested in other trial populations.

Yeah, Well, I think we can keep these guidelines simple going forwards. I think we need to reduce stratification in guidelines. And the key now, really, is for guidelines to find methods to enable us to implement SGLT2 inhibitors at scale globally. Amongst the large number of patients that I benefit currently, we see only about 40 to 60% of patients who really have an indication of use on them, and we need to improve that number.”