SGLT2i in the spectrum of CKD: A call for action

Welcome, everyone. I'll be speaking to you about SGLT2 inhibitors in the spectrum of CKD and what we need to do about bringing these therapies to patients. Firstly, my disclosures.

Just to sum up what you've already heard today, there's a broad benefit for SGLT2 inhibitors across a range of eGFR that you're looking at here, as well as across a range of albuminuria and of different clinical scenarios. The question for us is how we bring these agents to the broad population who are going to benefit.

We know that we need to consciously think about this. With RAS blockade, we still in the US, only had one in five patients receiving an ACE inhibitor or an angiotensin receptor blocker well after these agents were implemented. We want to do better than that.

Implementation science is about the science of how we implement research findings into practice. We've already proven that things work. How do we scientifically work out how to bring them to the people who benefit? Broadly speaking, there are three main components here. There's diffusion, which is passive dissemination of evidence. There's active dissemination to target audiences, and then there's implementation. For us to do better as a community than we did with RAS blockade, I think we really need to be thinking about actively implementing into clinical practice. We have the guidelines. We've covered the passive dissemination that KDIGO guidelines now say that first-line glucose-lowering therapy for people with diabetes and CKD is metformin and SGLT2 inhibitor. We know that there's going to be an update in the chronic kidney disease guidelines from KDIGO and I think we're all looking forward to seeing what the new findings are there.

In the meantime, we have seen an increase in SGLT2 inhibitors in people with diabetes without CKD. In the UK, we're up to around 30% of patients are receiving an SGLT2 inhibitor. That uptake has been really marked in the last five and so years. However, things aren't looking so good for people with CKD. With people with CKD, you can see we're well short of achieving that 30% level. These are patients who stand to benefit more than the population without CKD. We also know in high-risk patients, that's patients with heart failure, patients who clearly stand to benefit from an SGLT2 inhibitor uptake again lags. It's lagging behind the older therapies, RAS blockade and ARNIs, and so forth. We know from the strong results in the trials that these agents have a profound risk reduction and so we need to turn this around and make sure that they're being delivered to patients at high risk.

Why isn't this happening? Well, there are many reasons. You can read systematic reviews of barriers to implementation, but it helps to broadly think in terms of characteristics of the participant, the patient, characteristics of the provider, and characteristics of the health service system, and lastly, of course, the broad socio-economic context. If we fail to contemplate all the roles of all these factors in, we're likely to come short when we're implementing. Firstly, it's worth thinking about the providers. We've talked about patient characteristics like risk. Let's think about providers. Most people in the US will receive an SGLT2 inhibitor in primary care. Our focus on implementation should be in primary care. We also know that endocrinologists are prescribing most SGLT2 inhibitors by prescriber. They will prescribe 270 prescriptions of an SGLT2 inhibitor per year. That compares with nephrology where we're managing about six per year. That's something that we really need to improve, we are. There's been a 300% increase over five years to 2020 but we need to do a lot better. We know the patients who are treated are largely the lower-risk patients. Patients with chronic kidney disease or a history of heart disease, or with heart failure or recent hospitalizations are all less likely to be prescribed an SGLT2 inhibitor. There maybe that's a little bit of hesitancy and concern about risk, but I take it back to my opening comments. It's the people at the highest risk who get the greatest absolute benefit.We know that from the randomized studies.

Once we've prescribed our SGLT2 inhibitor, the next question is keeping patients on it while they're still appropriate to receive these agents. By and large, in the trials, we saw very small numbers of patients who dropped out of treatment. In the real world though, we're seeing much bigger numbers. Adherence and persistence at one year around 35% to 60% depending on the setting. That's, again, much better than we had with RAS blockade as I told you at the beginning of this talk. We still have a long way to go to match the benefit even that we saw in the trials. Let's think about individual nephrologist barriers now. There's been a survey that looked at problems that the nephrologist reported, both people who'd been practicing for many years and people new to practice, and the results showed what we'd expect. Some of the barriers are just simply lack of time and personnel to manage the side effects. Equipping practitioners with tools to help them there and practice support will be a benefit. There's a straightforward lack of experience and comfort levels. Lastly, there's financial barriers in some settings with high cost of copays. Now, what helps things that we are already doing, participation in conferences, tools like those that come from social media, and lastly, professional guidelines.

There are some tools, KDIGO has given a short succinct summary of things that you need to think about and educate the patient about when you're prescribing an SGLT2 inhibitor. This guide is in the guideline, and I'd refer you to that. Then individual societies are producing tools that help. This is one from the Agency for Clinical Innovation in Australia, and that is a guide for acute inpatient care. It'll tell you how you manage a patient on SGLT2 inhibitors, particularly how you manage to the fasting state when you're going to suspend use, and then importantly when the participation's going home, when you restart, or when you refer to the primary care practitioner to restart.

We know from the evidence in the trials you've heard earlier, SGLT2 inhibitors are safe and provide kidney and cardiac protection for people with diabetes and/or with CKD. We know that we are doing better at the moment than we did for RAS blockade, but uptake is patchy and there is a lot of unmet benefit there to be gained. What we really need is ways to safely keep patients on proven treatments, and that will require a better understanding, and we might gain that understanding through active implementation trials and other quality assurance activities.

Thank you.