Jeremy
So hello, I'm Jeremy Levy, consultant nephrologist at Imperial NHS Trust.
Andrew
And I'm Andrew Frankel, a colleague of Jeremy's also working at Imperial College Healthcare NHS Trust. And welcome to another episode in our series of podcasts For Kidneys Sake. Today we're going to focus on a subject that may not immediately seem to be related to chronic kidney disease. And that is the updated guidelines from NICE on the management of type 2 diabetes.
Jeremy, perhaps you can start us off by considering why are we discussing this today?
Jeremy
Well, apart from Andrew, your total obsession with diabetes and expertise in diabetes and kidney disease, I think you'd like every episode to be about this topic, but no, that was very unfair of me. So our audience will really, really understand that diabetes and chronic kidney disease are linked. I think we don't need to say that at the beginning. But the proportions and the numbers of people with a kidney problem who've got diabetes is really rising fast. And it's reaching massive proportions.
So that in some places, both in the UK and round the world, over 50% of people with chronic kidney disease are living with diabetes. So anybody managing chronic kidney disease does need to know something about diabetes as well. And Andrew, you've previously pointed out that in some bits of the world, such as the Gulf, those figures are 70 and 80% of people with diabetes causing chronic kidney disease. This is a huge issue.
Andrew
Yep, it's a growing and
really serious one.
Jeremy
It is. And then the other two things which I think these new NICE guidance really emphasise for the first time is firstly, as kidney function declines, the choice of therapy to actually manage blood sugar also alters and changes, and that's sort of been ignored in the past and yet is really, really important. And then finally is we've sort of talked about in many of these podcasts the presence of diabetes and chronic kidney disease.
Increase your risk of cardiovascular disease; hence this term cardiorenal or cardio-kidney metabolic medicine and disease. These three are really intertwined and once again that these new nice guidance aren't just you know banging on about glycemic control and HB1Cs, but talking about sugar management in the context of these three issues. So for me, just looking at these sort of even just cursorily, this is a fundamental change and thinking about the treatment of diabetes is about Diabetes in the context of chronic kidney disease, obesity, heart failure, cardiovascular disease, and glycemic control is sort of not the front end of these guidelines. That be my sort of initial look at the guidance.
Andrew
Yeah, I completely agree, Jeremy, and as you can imagine, I'm both personally and professionally delighted with these new guidelines. And I'm gonna sort of emphasise something you've already said, but I think is a really important takeaway. It seems to me really that NICE has effectively repositioned type two diabetes as a cardiorenal metabolic disease rather than simply a disorder of glucose.
I would also add as an aside that there has recently been published the NHS Modern Service Framework for Cardiovascular Disease, and that now has within its title a cardiovascular kidney metabolic approach. So this is very much becoming part of the kidney landscape and is very, very relevant to primary care where most of these patients sit. And I think we should ensure that we cover cardiovenal metabolic disease as a conglomerate rather than dealing with them in silos.
Jeremy
Andrew, let's stop waffling it's not me, of course it's you. Let's stop waffling about the the principles. Give us some details. What do these new guidelines say about actually how to manage diabetes?
Andrew
Okay, so one of the first messages, although this doesn't only relate to people who already have kidney disease, but from a kidney perspective is a really important change, is the guideline has now placed SGLT2 inhibitors, which we think of as kidney medicines, as a first-line or foundational treatment across multiple patient groups because of their cardiovascular and renal protection.
And not simply for their glucose lowering effect. They are started with metformin and less contraindicated. Furthermore, NICE recommends continuing SGLT2 inhibitors for their cardiac and kidney benefits even when glycemic targets are not reached. In other words, they should still be continued even if the drug does not lower blood sugar enough.
Jeremy
That's a really big change, Andrew. Actually it's come through really fast on the back of trials of these new drugs. so that you know that SGLT2 inhibitors with metformin as foundational treatment, really, really big change. so I think one of the key questions therefore clinicians need to ask is whether a patient does have chronic kidney disease and then what about the sort of GFR number, the the extent of their chronic kidney disease.
Because we've now got to think about that in the context of these new drugs. And for people with existing or established or diagnosed chronic kidney disease, the treatment of their diabetes then becomes dependent on their kidney function, not just their blood sugar control, their HB1C That's my reading bit, isn't it? So people who've got well preserved kidney function, so that's GFRs actually above thirty, so they may have chronic kidney disease, but they've got still preserved GFRs to a significant degree. What you've just said is is unchanged, isn't it? It's gonna be an SGLT two inhibitor, first line, and ideally with metformin. That's when your GFR's above thirty. I'm reading that right Andrew aren't I?
Andrew
Correct.
Jeremy
And then once the chronic kidney disease has become more advanced, that's when we start to get a little bit more complex. And I suggest that once the GFR's between 20 and 30, and that's really very significant chronic kidney disease, then you offer one of these drugs, these DPP4 inhibitors. Those are the gliptins. So that's together with the SGLT2 inhibitor. So this is a gliptin. With dapoglyflosine or empoglyflasine when your GFR's between twenty and thirty. And in this context, any of the gliptins work, don't they? That's linoglyptin, cytoglyptin, vidiglyptin, saxoglyptin, there's whole range of gliptins, and most of these are once a day drugs. So GFRs 20 to 30, you're using an SGLT2 inhibitor together with a gliptin. We'll come back to metformin in a moment.
Andrew
Yeah, absolutely right. I perhaps should just emphasize that we keep saying together with an SGLT two inhibitor, but of course NICE recognise that a GFR thirty the SGLT two inhibitor is not providing any glycemic benefit, but they recognise you still need the drug because you're trying to prevent the complications of diabetes. But yes, absolutely right about the gliptins.
Jeremy
Okay, and then we get down to a GFR's less than twenty. Of course this is very significant chronic kidney disease. And my understanding, Andrew, is that when your GFR's below twenty, and they've sort of written some slightly woolly wording, one should consider a gliptin, a DPP four inhibitor, at first, but then also think hard about pyoglitosone or insulin if your blood sugar control is not being controlled at that level of a GFR less than twenty.
Andrew
Yeah, that's absolutely right. And I think what NICE are trying to cover is the fact that people who've got a more advanced kidney disease, the range of drugs we have available to us is significantly reduced. and my experience is that if glycemic control is poor with the DPP four inhibitors, they often quite can't hit the mark. You you do need to reach for pyoglitosone or in even Insulin in this situation.
Jeremy
That's right. And and the other really important thing you mentioned before is that issue that in this context, GFS less than thirty and certainly less than twenty, the SGL two inhibitors are no longer offering glycemic control, but they're offering that cardiovascular and renal benefit out with and that's why they shouldn't be stopped. You said that before, but I was gonna repeat it because it's such an important point, isn't it?
Andrew (08:58)
Absolutely. I I should add some physiology here. managing glycemia in people as their kidney function declines is difficult because of two opposing issues. Firstly, the kidneys are actually responsible for metabolising insulin. So as your kidney function declines, any insulin in your body, whether that is endogenous, because you still have that in type 2 diabetes or exogenous lasts much longer.
It hangs around. And that means you need less insulin, as any insulin given is going to last much longer in people with advanced CKD. But the other side of the coin is that as GFR declines, insulin resistance increases. And the balance of these two issues varies individually between different patients. And that's what makes it so difficult.
I would highlight though that once a patient has got a GFR of below twenty, it's more likely they're going to be followed up in secondary care. So you might say as a primary care clinician, Whew, thank good this is a problem for secondary care. Although I would just say many nephrologists who are seeing these patients think the patients have glycemia is being managed by their GP. And that's one of the confusing issues that we have.
Jeremy
So Andrew, practically what does this mean? You've already told us beautifully that bad kidney function is insulin hangs around more but more insulin sensitivity essentially. So what do people do when the GFL drops below twenty in terms of dosing of insulin?
Andrew
Again, there's no one rule for everyone, but broadly you need to tweak that insulin down. Most patients need a reduction of dose of around thirty percent as their GFR drops below twenty, but you have to tweak it over several months to get it right.
Jeremy
That was a really important point. So GFR falling less than twenty for people on insulin often need a dose reduction of twenty to thirty percent, maybe not in one go, because of all the things we've talked about. Really helpful, Andrew. So we're gonna come back to Metformin. as you know, Andrew, I really love metformin and we we need to talk about what the guidelines say and the practicalities because metformin's a old drug, it's been around for way, way over sixty years.
And it still has very good evidence for cardiovascular benefits and for managing HbA1c when managing blood sugars in diabetes. And the first thing I want to say is is to remind everybody metformin is not in itself nephrotoxic. The message out there is that it sort of harms kidneys, especially when we start to say to patients, you need to stop this drug. And they sort of think it's doing any harm. It is not nephrotoxic. The problem is.
That when your GFR declines about less than 30, metformin tends to hang around more because it's renally excreted. And this has been associated with an increased risk of lactic acidosis. But almost certainly it's not metformin itself driving it, it's metformin in the context of very low GFRs in acutely unwell patients who are volume depleted and often septic. And in that setting.
There's a small increased risk of lactic acidosis when you've got metformin on board. And so NICE in this new guidance have been clear that even though we're using metformin at the outset, and we still should be, that once the GFR drops below 30, then you should be stopping or withdrawing metformin, and patients should have good sick day guidance to make sure that they hold it for a couple of days if acutely unwell.
But the message to patients shouldn't be that metformin is a problem. It's not the cause of their kidney decline. It's as their kidneys decline, metformin's hanging around and we need to think about stopping it. But it is a good drug prior to that.
Andrew
I also and I think you know that I have a s particular view on this, Jeremy, that I sometimes when I'm asked about this from referrals that come into our service, that you have to remember that when you stop metformin there are a group of patients who really are very reliant on metformin and we've already said it's not easy to identify treatments at GFRs of less than thirty. And so what I have sometimes recommended
Is that if the patient is significantly overweight with BMIs of say over 35, their real GFR is probably greater than their estimated one. And I advise that as long as the patient is stable, they haven't been admitted in the last year, is able to understand and adhere to good sick day guidance, then it's reasonable to discuss it with the patient and make a decision to continue the metformin down to a GFR of 20.
At which point it really must be stopped. Jeremy, what are your thoughts about the advice that I've always given?
Jeremy
So you and I really disagree, Andrew, but I am gonna disagree with you here. I think everything you've said is absolutely factually correct, but I think it's so nuanced it becomes a bit tricky. So personally, I just use thirty as a single cutoff, a GFR of thirty. And if the GFR drops below thirty, you need to stop metformin I mean it's not an emergency, don't phone the patient in the middle of the night.
But your discussion's absolutely correct, but I just think it becomes very tricky for the practice pharmacists for patients, for the world out there. So I just use thirty. GFR drops below thirty, think about the diabetes control, get them off metformin, whether they're overweight or not so overweight. But maybe Andrew it's just because you're such a good at explaining this that that I'm just failing miserably.
Andrew
Well, you know, Jeremy, sometimes you're very wise and sometimes the pragmatic has to trump the academic, and perhaps I should give that more thought in future. I just want to focus now on one other important aspect of the guidelines for people with kidney disease. The guidelines make important points about the use of GLP1 receptor agonists. Laraglitide, delagglitide.
Symagotide, as they are also called Victosia, Trilicity, and Ozempic. As one would expect, they recommend that these drugs are used earlier, introduced earlier for people with diabetes and obesity. But there is another really critical point in relation to cardiore renal metabolic disease. NICE are clear that if the person with diabetes also has established atherosclerotic cardiovascular disease that could be stroke, heart attack, acute coronary syndrome, peripheral vascular disease, they should receive some maglatide alongside metformin and an SGLT2 inhibitor
And given the frequent co-location of diabetic kidney disease, that is, people with diabetes and kidney disease, with established cardiovascular disease, this is something that all clinicians will need to be aware of, and we're going to need to consider how we introduce this rapidly and effectively, as nice or clear, and indeed the studies are clear, and we cover this in previous podcasts, that this will provide significant cardiore renal benefit. This is actually a huge change.
And it's in the small print, but it's actually very clear. and it's a pair area that I hope we're gonna move forward with very quickly. also, of course, we're gonna have rafts of new GLP1 receptor agonists in various forms coming along.
Jeremy
it is a big change, Andrew, isn't it? And for GPs that's gonna be a lot of extra work, it's gonna be a lot of extra money because these are not cheap drugs are they? But even though we've left it to end, that's a really important change.
Andrew
Absolutely. And Jeremy, I I was gonna give you and I still will give you, the chance for the final three takeaways.
Jeremy
Well yeah, it has to be me actually you wouldn't get it to three, Andrew. Right, my three takeaways from talking about diabetes and the new diabetes guidelines, which I hope has been useful. So so firstly, I think we sh we need to all change our view about diabetes as being just a disorder of blood glucose. This is a cardiorenal metabolic problem, and these new guidance absolutely think about diabetes in the context of chronic kidney disease, heart failure, cardiovascular disease, obesity when thinking about diabetes treatment. So it's not just people with diabetes, it's people with diabetes and their comorbidities. Secondly, SGLT2 inhibitors that we loved as kidney drugs are now foundational therapy for people with type 2 diabetes, often with metformin, if your GFR is over 30. So first line treatments shifted really very dramatically. And then thirdly, given I'm only allowed three points, that last point I think really remember
The GLP one receptor agonists are really strongly recommended for all people with type two diabetes and established cardiovascular disease because they reduced morbidity and mortality. They'd be my three points, Andrew.
Andrew
I completely agree and surprising I'm not gonna add anything to that, Jeremy. And so thank you, Jeremy, and thank you audience for listening.
Jeremy
It's been great, Andrew- a great discussion. we should remind everybody that all of our back catalogue, as we're meant to say, of podcasts are available wherever you get your podcasts. they're still all brilliant. We've updated a few of them recently. Go listen now, for Kidenys ' sake. an excellent range of of learning and revision for everybody out there.
