Finerenone and Semaglutide now on team kidney

The For Kidneys Sake podcast series is brought to you by Imperial College Healthcare NHS Trust and North West London Integrated Care Board (NWL NHS)

For years, diabetic kidney disease felt frustratingly static: ACE inhibitors, ARBs… and then very little else. 

In this episode, Porf Jeremy Levy and Dr Andrew Frankel unpack why that era is finally over. With SGLT2 inhibitors already changing practice, attention now turns to two newer players finerenone and semaglutide and how they meaningfully reduce kidney failure, cardiovascular events, and even mortality. The hosts explore why finerenone is not just “spironolactone with a new name,” and why nephrologists (and primary care clinicians) suddenly find themselves spoiled for choice.

But with progress comes complexity. How do we sequence these drugs? Who benefits most? How do we explain to patients why another tablet matters when they “feel fine”? 

From potassium monitoring and GFR thresholds to lifetime risk conversations and real-world prescribing barriers, this episode is a practical, optimistic guide to modern diabetic kidney disease care and a rallying call to help patients avoid dialysis, heart attacks, and strokes in the decades ahead. 

Top 5 Takeaways

1. Diabetic kidney disease has entered a new treatment era - After decades of stagnation, we now have multiple therapies that genuinely slow progression and reduce hard outcomes.

2. Finerenone is different from spironolactone - It’s kidney-protective in type 2 diabetes, with fewer endocrine side effects and strong trial evidence.

3. Hyperkalaemia risk is real but manageable - Baseline potassium, GFR, NSAIDs, constipation, and follow-up labs matter more than fear.

4. Semaglutide is now a kidney drug too - Beyond glucose and weight, it delivers major renal, cardiovascular, and mortality benefits.

5. The biggest challenge is communication, not pharmacology - Helping patients understand long-term risk and benefit is central to success.

Resource Links:
NICE GUIDELINES [NG203] chronic kidney disease: assessment and management Overview | Chronic kidney disease: assessment and management | Guidance | NICE

Northwest London CKD guidelines for primary care Chronic kidney disease (nwlondonicb.nhs.uk)

The purpose of this podcast is to inform and educate health care professionals working in the primary care and community setting. The content is evidence based and consistent with NICE guidelines and North West Guidelines available at the time of publication.

The content of this podcast does not constitute medical advice and it is not intended to function as a substitute for a healthcare practitioner’s judgement.

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Transcript

Joana Teles 

For Kidney's Sake makes kidney disease management easy. For Kidneys Sake is for primary care clinicians. For Kidney's Sake is nice, consistent, short and sweet. Welcome to For Kidneys Sake brought to you by Northwest London NHS Kidney Care Team.

Jeremy 
So, hello, I'm Jeremy Levy, Consultant Nephrologist at Imperial Healthcare NHS Trust.

Andrew 
And I'm Andrew Frankel, a colleague of Jeremy's at Imperial College Healthcare NHS Trust. And this is another episode of For Kidneys Sake.

Jeremy 
So today it's going to be all about sort of diabetic kidney disease. We've talked a bit about this before and Andrew and I have been talking quite a lot about advances in the last five years in relation to diabetic kidney disease and having had absolutely no new treatments really since the introduction of ACE inhibitors and angiotensin blockers which is way over 15 years ago. We now have really quite a large range of new treatments introduced which are benefiting people both with diabetes and diabetic kidney disease. And these include not just the SGLT2 inhibitors, which you'll all know about, and we did a previous episode all about them, the glyphosins. But what we're going to focus on today is now we've got the new Mineralocorticoid receptor antagonist, finerenone. And also joining the party with finerenone is semaglutide. And I know from my own personal experience, nephrologists are feeling really fairly overwhelmed by all of this, how to use these drugs and new information. And so we imagine this must be challenging across the spectrum and especially into primary care.

Andrew 
I completely agree, Jeremy, it's wonderful to have all these new treatments to delay progression of kidney disease in the context of diabetes. And indeed, there are now murmurings in some of the really major journals of nephrology that there is a potential with all of these tools to move from delaying progression of diabetic kidney disease to actually preventing the need to dialyse in the context of diabetic kidney disease. So it's really exciting, but it's also challenging for a variety of reasons. First of all, there is a challenge of understanding how and when these drugs should be started and then the challenge of trying to explain to a patient with diabetic kidney disease how they might benefit from receiving so many medications.

Jeremy 
That's exactly the point, I enjoy both of those I think. The latter are actually really important in our discussions. And I suspect that we can help primary care a bit can't we in this conversation, in this podcast, and that's what we're going to try and do. So let's start with finereone the drug that's been on the market now for a few years and it's been fully approved for use in many countries around the world including the UK for diabetic kidney disease. So that's finereone.

Go on, tell me a bit about what it is and why is it different from the older mineralocorticoid receptor antagonists that actually particularly spironolactone that primary care and us have been familiar with for years and years and of course the other older drug is epileronone. Why is pheneronone different? Why should we be using it? Tell me something about that.

Andrew 
So Jeremy, finerenone is fundamentally different from those other types of mineralocorticoid receptor antagonists, such as ⁓ Spironolactone and indeed eplerenone. It is very specific for the mineralocorticoid receptor with absolutely no cross-reactivity to any of the other steroid receptors. And this is important, especially for the side effect profile.

There are also some other pharmacological differences, including shorter half-life, lack of active metabolites. From the clinical perspective, what is crucial is whereas there has never been any data or evidence that either spironolactone or a pleuronone protect against progression of kidney disease by reduction in the rate of progression of decline in GFR, there is now robust evidence for finerenone for people with type 2 diabetes and progressive kidney disease. The evidence is good enough for the drug to have been given a positive, nice technical appraisal in relation to this indication.

Jeremy 
So, even though I believe you all the time, Andrew, I did some reading and have found this randomised control trial, which was spironolactone versus placebo in patients with progressive chronic kidney disease, in fact showing no benefit at all of spironolactone in progression and only side effects. So, you have convinced me the data is out there. Finerenone is not the same as spironolactone in terms of diabetic kidney disease and progression and kidney protection. So...

How should we be using finerenone

Andrew 
So Jeremy, you are always quite rightly my sort of note of caution when I get over enthusiastic about some of these trials, but I'm pleased I've convinced you on this one. So we should, we can and we should be adding this drug, phenyloinone, to significantly reduce the risk of progression of diabetic kidney disease in people with type 2 diabetes, who are already on an ACE or an ARB together with an SGLT2 inhibitor. Caveat here, you can use it if they are unable to tolerate one of those two classes of drugs and who despite being on those agents have ongoing renal risk in the form of persistent albuminuria. And in the UK, you use it between a GFR of 25 to 60.

Patients don't get the endocrine side effects we commonly see with spironolactone such as gynecomastia and they get the benefit. 

Jeremy 
That's really helpful Andrew and I agree I've been using it quite a lot I'm not seeing any of those endocrine side effects that we used to see with spironolactone either in real use But it isn't a wholly innocent drug is Andrew. This is a mineralocorticoid receptor antagonist So like spiro adding it to an ace or not must surely cause the potassium to rise. We're not seeing problems with hyperkalemia

Andrew
Yes, Jeremy, you're quite right to call me out here. That is a significant issue that needs to be addressed.

Like all MRAs, fineranone will result in an increase in potassium. And there are some simple ways to reduce that risk of that problem occurring. You shouldn't think of starting fineranone if the baseline potassium is already 5, without seriously thinking about actions to manage this first. But it's also noted that in people with more preserved kidney function, particularly in the studies GFR is above 45, there is actually very little risk of hyperkalemia with fineronone. Advice really is to monitor kidney function of potassium two weeks after starting fineronone at a dose of 10 milligrams and then if the kidney function is well preserved GFR is above 45 and potassium less than 4.5, you can increase the dose to 20 milligrams.

Otherwise, if you are concerned, you can maintain the 10mg dose.

Jeremy 
That's again really straightforward and helpful Andrew. So a small risk of hyperkalemia, very little if the baseline potassium is less than five millimoles per litre and also importantly very little risk if your GFR is relatively preserved above about 45 and those are often the younger people with proteinuria who are really keen to protect thinking forwards 20, 30 years over their lifetime.

And we should add shouldn't we our usual comments. It is possible to sometimes predict and mitigate patients in whom this may be a problem. So make sure they're not using non-steroidal anti-inflammatory painkillers. Shouldn't be if they've got kidney disease nor on any other drugs that might raise potassium. Trimethoprim comes to mind. I learned from you the other day constipation of course tends to drive hyperkalemia to a degree. So thinking about that for patients as well. And

We know that diet isn't the most important thing, but actually just some advice that patients shouldn't be consuming lots and lots of potassium rich foods. But diet's important to keep on that balance of lots of plant-based foods and a range of stuff. So lots we can think about.

Andrew 
Yes, and that's definitely now a drug that should be being added to our armatarium in relation to managing diabetic kidney disease. And I think you sort of hinted this, but a key question for primary care is why are we adding this additional drug? What are we trying to do?

Jeremy 
Sure, and of course, from a patient perspective, it's another tablet, and it'd be nice to have combination drugs, and I'm sure we will in the future. But this is about reducing patients' risk of heart attacks, strokes, as well as dialysis. These are bad outcomes and we can explain this to patients quite well can't we? It's not just that this is going to make them feel better because they won't feel different but it is going to stop them hitting dialysis or getting serious and significant, cardiovascular disease in the near future, in over the next 10 or 15 years and the trials were even shorter. So I think it is going to be really important to think about it and then think about the patient in front of us because again this is going to be most important for the younger patients with proteinuric kidney disease. If you're 80 years old and your GFR is 45 the benefits going to be minimal but a 45 year old with a GFR of 45 got a huge amount to gain and of course this is the nuance of primary care and us looking after patients and not just following a guideline thinking about the patient in front of us and being aware that the protein-eric kidney disease gives you a significant risk over lifetime especially for younger people.

Andrew 
Jeremy, absolutely. It is of course a pity that there's a bit of a postcode lottery around the country in how this drug is being initiated. Some sectors have it as a green drug and primary care can start this with the appropriate guideline that we've just described. And other places require secondary care, not just initiation, but sometimes outpatient attendances for six months. So it's really variable.

And I think as we get more confident about using this drug and we actually realise it's easier to use than sparing a lactone, I'm hoping that primary care will grasp this and use this to help prevent progression of diabetic kidney disease.

Jeremy 
Fantastic! So, finerenone. We should very strongly consider adding finerenone in people with diabetes, chronic kidney disease and ongoing proteinuria despite ACEs, ARBS and STLT2 inhibitors. But while we're all trying to get our head around finerenone, Andrew, you now tell me there's another kid on the block. Semi-glutide has now been shown to have significant cardio-renal protective effects on top of other things and on top of its treatment for diabetes and obesity.

And I gather this is now pretty clear evidence. Tell me about that.

Andrew 
Yes, you're right. Of course, one the most controversial areas of this is whether you pronounce it as semaglutide or semaglutide, but let's not go down that rabbit hole, okay? You're absolutely right here. The major trial called the FLOW trial was a study that looked specifically at semaglutide in people with type 2 diabetes and evidence of underlying kidney disease, reduced GFR and albuminuria.

They were randomised to either receive semaglutide at the standard dose and up to 1mg or placebo on the background of ACE and ARBs with a significant number also on SGLT2 inhibitors. In this study, the patients treated with semaglutide had a significant reduction, that's 24%, so greater than was seen in the ACE and ARB trials in the early 2000s, in progression of hard renal endpoints and also a significant reduction in cardiovascular events and a 20 % reduction in overall mortality in the time of the study.

Jeremy 
There's mortality benefits we're seeing in these new trials Andrea really amazing aren't they because these are short term studies essentially two or three years and yet there's benefit on death rates so these are just amazingly important effects and that reduction you talked about is sort of exactly the same as we saw with the earlier trials for the glyphosins in kidney disease and it's a pity the studies you talked about the patients weren't all on those drugs as well and of course I'm getting none wrong Finnerone at the same time.

Andrew 
You're right, absolutely, and this is another question we're going to have to grapple with over the next few years. It's an important study. It's given us a strong reason to get patients with diabetic kidney disease treated, particularly perhaps those who are more overweight, to provide long-term kidney protection. And now with all these treatments, what we are going to need to think about is how we sequence the addition of these drugs.

And from this I think we're going to learn a lot from our colleagues who manage heart failure, who also have four sets of treatment for heart failure with reduced ejection fraction. And I note that they've now moved over a short period of time to get patients onto maximal therapy, all four pillars, as speedily as possible.

Jeremy 
I'm sure you're right, Andrew, this is going to change quite quickly in kidney disease as well. The moment we have got the more sequential approach, haven't we? Starting with atrial ARBs, rapidly followed by SGLT2s and then considering fineridone with or without semaglutide. But you're absolutely right. I'm sure we're going to learn much more if we can do this quicker. It's easier for patients, it's easier for primary care and health care systems. And that whole sequence may be much easier to do in the future. So I think this is going to be very, very important.

The finereone and SGLT2 combination is really important, usefully isn't it? Because it minimises the risk of hyperkalemia. So that's a very helpful thing. But the really important thing is going to be here, it? Talking to patients, making patients understand why we're giving them lots more drugs. And some of the frightening outcomes, they...

They are much less likely to need dialysis in the future if we can treat them properly. They're much more likely to live longer and see their children and grandchildren. And it's a bit like the conversation we had decades ago, adding some statins to multiple blood pressure drugs. And it's about engaging patients, isn't it? And they are going to be on lots of medicines, but that have got important protective effects.

Andrew 
Indeed, and as a nephrologist and people have probably gathered this from the way I've delivered this podcast, I'm incredibly enthusiastic about all these new treatments. They really will have an impact on CKD progression and on reducing cardiovascular events. But I do need to be clear. I really do understand that for primary care, where most of these individuals are sitting, this is going to be very challenging and I know we're trying to do this locally and I hope other nephrologists around the country will take this up. We have got to really support primary care in understanding how to safely, effectively and efficiently add these new medications.

Jeremy 
I agree of course Andrew. So that's been really helpful. Gon, this has been your love of your life. Give me three takeaways that you want to convince me I should remember when I go and finish my breakfast.

Andrew 
So Jeremy, I don't want to interrupt your breakfast so I won't be long. Try to ensure that you have a clear understanding of the risks that an individual patient has in relation to their chronic kidney disease and declining kidney function, and their likely need to dialyse in their lifetime. Do they have an elevated urine ACR, proteinuria or losing GFR?

Then be able to share that with patients so they can understand why multiple therapies may be needed to help reduce their risks for future harm. Try and encourage patients to see these treatments as friends and don't hold back where you have... sorry, and encourage patients to see these medications as friends.

And don't hold back where you have the opportunity of improving someone's long-term health and avoiding the need to dialyse or to have a kidney transplant in the future.

Jeremy 
Andrew, thank you very much. Great discussion. I've learned lots this morning. ⁓ Hope our audience have as well.

Andrew 
Thank you, Jeremy.

Joana Teles
Thank for listening. We hope you enjoyed this episode. All information is fully consistent with NICE and Northwest London guidelines. You can find out more in the show notes and contact us with any suggestions or questions. Send us a text using the text function at the top of your show notes. Thank you for listening to For Kidneys' Sake podcast and we see you at the next episode.