Therapeutic Guidelines Diabetes

The way we label things and the language we use really does matter, and I think it really sets the tone to how we think about the management of diabetes.

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Hi, and welcome to this Australian Prescriber podcast. I'm Dr Justin Coleman, a GP in Inala [Brisbane], and also have a few other diabetes hats to my name, not least having edited the Diabetes Management Journal for some years. But with me, I have a real expert in diabetes, and that's Dr Tilenka Thynne, who's an endocrinologist and clinical pharmacologist at Flinders Medical Centre in Adelaide. Welcome to our humble podcast, Tilenka.

Thanks, Justin.

Great to have you. We're talking today about the new update of the Therapeutic Guidelines Diabetes. And interestingly, this is the first guidelines where it's officially a living document. So rather than waiting, whatever it is, a year, 18 months for a working group to get together and update the entire thing, I gather we're updating this one bit by bit as new evidence comes to light.

That's right. The diabetes space, like many of the areas of medicine, it's quite a fast-evolving space. And when we did go back and looked at what has happened in that short time from when we last did the Therapeutic Guidelines Diabetes, there were quite a few changes just in that time. So I think as changes evolve, it's nice to be able to update those and keep it all relevant.

Great to be part of a living guideline. Let's start where people expect us to start, which is, what drugs do we use for diabetes? Metformin remains front and centre. It's been around almost 100 years. It's effective, it's safe. We still start with it.

We do. We still start with metformin. It's old, it's trusted, it's cheap, it's safe. It does have a long history of safety. There is evidence that it may reduce cardiovascular events and cardiovascular death. We also know the importance of getting tight control really early on, right from diagnosis, and being able to then maintain that tight control. In those original trials back in the '90s, the UKPDS [UK Prospective Diabetes Study], they really showed that importance of tight control early, and that legacy effect of then ending up better years down the track still, with a reduction in complications.

So we don't want people to think if they need to go on to metformin or other treatment, that they're failing. We want them to start with diet, exercise, metformin straight away, and do well and get that really tight control right from the beginning.

Yeah, so that positive approach. And I guess any pharmacist or general practitioner who hasn't had their head under a rock in the last 5, 10 years would be well aware that there's an emerging number of drug classes, and the evidence for that is increasing all the time. And some of the older ones, besides metformin, the use of them is fading a bit in light of the new medications. So of these new classes, there's a lot of information in Therapeutic Guidelines about which ones to choose. Can you take us through some of those?

We used to have it quite clear that we had a first-line drug, a second-line drug, a third line. Whereas now, we've still got metformin as our first line. But then often, you're sort of thinking, "Right. Well, what's second?" And it really comes down to that individual patient, as to what best drug is going to be next. And there's a number of things we consider in that. If you've got somebody who's got an HbA1c and glycaemic levels that are way above their target, you might want to think that even just starting one drug's not going to be enough, and you might want to go straight to two [drugs] to aim to really get that good control. So you want to think about how bad or how high is somebody's blood glucose. Because we know that the new drugs, a DPP-4 inhibitor does not have as much glycaemic control or glycaemic benefit properties as, say, a GLP-1 [receptor] agonist.

So we need to think about how high are their blood glucose [concentrations], but we also want to think about all those other patient factors. What’s the patient’s cardiovascular risk? Do they have heart failure? Do they have chronic kidney disease? Is there going to be a clear indication for starting an SGLT2 inhibitor in a patient who’s at high cardiovascular risk, or has heart failure, or chronic kidney disease? Or in a patient, again, who’s at high cardiovascular risk, there’d be a benefit of starting a GLP-1 [receptor] agonist in that setting as well.

We also consider what their risk of harm from medication is. So an example of that would be somebody’s hypoglycaemic risk. So we know that a sulfonylurea or insulin is going to be at higher risk of causing hypos, and they’re patients who we might want to avoid that in.

Is it true to say that, really, those are the only two hypoglycaemics that have a genuine risk in normal circumstances for hypoglycaemia?

That’s right. They’re really the two drug classes that can cause hypoglycaemia. You might find, in combination, others will add to the risk. So if you’ve got somebody who’s already on insulin and you’re adding in a GLP-1 [receptor] agonist, they might require reduction in their insulin to avoid hypoglycaemia, but the GLP-1 [receptor] agonist itself isn't causing that hypo risk.

And then of course, you alluded to it, the cardiovascular and renal benefits, and I guess they also guide drug choice.

Very much so. So if you've got somebody who has heart failure, we're now using SGLT2 inhibitors outside of the setting of diabetes for their heart failure management alone, and benefits. So any patient with diabetes who has heart failure, we'd be thinking about starting an SGLT2 inhibitor in there. Same with chronic kidney disease, there's really good evidence now for the SGLT2 inhibitors in that area as well.

And we're also then thinking about their atherosclerotic cardiovascular risk, where both the GLP-1 [receptor] agonists and the SGLT2 inhibitors have great data for secondary prevention of atherosclerotic cardiovascular disease. So if somebody already had established cardiovascular disease or were at high risk, then I'd certainly want them to be on an agent that reduced their risk of a further event or even reduce their risk of death. And that's really independent of their glycaemic control. So we really think about it in two ways. We think, what's this drug going to do from a glycaemic point of view? But we're also thinking about what independent positive effects is this drug potentially going to have for this patient?

In the last year or so, the talk of the town has been about weight loss. Tell me about the weight loss associated with a couple of these newer classes of medication.

It is really quite exciting. We've always talked about weight loss as being something that we try and get our patients to strive to achieve, and it's not easy. So in the past, medications like sulfonylureas , insulin actually cause weight gain, which is kind of the opposite to what we're often trying to achieve. So the SGLT2 inhibitors, by actually causing calorie loss from glycosuria, are associated with some weight loss. It's quite modest. It tends to be only a few kilograms. But the GLP-1 [receptor] agonists are being quite well established now as weight loss [drugs]. So the weight loss can vary, but for some people, it’s up to 10% body weight or more, and it can be quite variable for individuals.

Some of the GLP-1 [receptor] agonists, such as semaglutide, which everyone's hearing about with the brand name Ozempic, can be associated with quite significant weight loss. There aren't great studies directly comparing the various GLP-1 [receptor] agonists, but the new guidelines go into some detail as to comparisons as well.

Thank you. Moving on now to prediabetes, which I must say is a diagnosis which has never truly excited me as much as some other people, in the sense that I seem to spend so much of my life talking about weight and cardiovascular risk and improving lifestyle, regardless of whether someone is defined as having prediabetes or not. But the latest guideline does give that specific definition now, of 6.0 to 6.4% HbA1c being the threshold for prediabetes.

We've long thought about impaired glucose tolerance, and we've had guidelines as to fasting hyperglycaemia that's prediabetes, and classified it based on an oral glucose tolerance test. But in these guidelines, we actually move towards an HbA1c diagnosis of prediabetes. And as you say, it's not a disease itself, but it really helps define a group of people who are at much higher risk of going on to develop type 2 diabetes.

And what we also know is that these patients are at higher cardiovascular risk even before they tip over and actually have that diagnosis of diabetes. It's a really important group of patients to recognise, and to try and institute lifestyle changes to reduce the risk of tipping over and developing type 2 diabetes. But also, really think about managing their cardiovascular risk as a whole.

Yes. And I do note for the punters that the range is actually extended in Aboriginal and Torres Strait Islander people, and Māori and Pacific children and adolescents. And it's down 5.7 to 6.4%, so the prediabetes starts at a lower level than the 6.0 for the rest of the population.

Well, Justin, you've been heavily involved in this area, as a lead author on the diabetes chapter of the national guide. Can you tell us about those guidelines and the implications in the Aboriginal and Torres Strait Islander population?

Thanks, Tilenka. I do author the chapter in the Preventative Health National Guide for Aboriginal and Torres Strait Islander people. And in fact, I've authored the last couple of editions, and there's a new one coming out hopefully later this year. The big changes there are that earlier screening, so we used to recommend from the age of 25 years, which is the current screening age for Aboriginal and Torres Strait Islander people. And we're lowering that now to the age of 18 years, suggesting an annual screen, usually in practice using HbA1c although there are multiple ways of screening. And the other change is that for those at higher risk, in fact, we start from the age of 10, and that's where the population risk is markedly increased, and there's a number of factors you can look up in the guidelines as to who is at higher risk. So that's in recognition that the prevalence is about three times higher, age adjusted, in that population.

Moving on from something I know a lot about, there's something you know a lot about, Tilenka, and that is pregnancy. So we've got women with pre-existing diabetes and gestational diabetes. Of interest to me, and many listeners will probably know this already, but I didn't, it's now routinely recommended that women with pre-existing diabetes who become pregnant take aspirin and calcium supplementation.

That's right. We know that women with type 1 and type 2 diabetes coming into pregnancy are at higher risk of elevated blood pressure, and that includes pre-eclampsia. As pre-eclampsia prophylaxis, we're now recommending both aspirin and calcium supplementation from 12 weeks gestation.

In addition to that, these latest guidelines have updated their blood glucose targets and their HbA1c targets for before conception and also during pregnancy. And that's to make sure that we're in line with the ADIPS [Australasian Diabetes in Pregnancy Society] recommendations as well.

And gestational diabetes, there's discussion of that in the Therapeutic Guidelines

Yes, there is. It's very well covered in the guidelines. Traditionally, there've been changing diagnostic criteria and changing targets. And that's all very clearly laid out in the latest guide as well.

Right from the start of the SGLT2 [inhibitors], there were some warning signs about diabetic ketoacidosis, and the evidence evolves for those every year. And what’s this latest living guideline addition have to say about the SGLT2 [inhibitors] and their safety?

We know that these are really good drugs with a lot of positive benefits and outcomes, but the risk of diabetic ketoacidosis associated with the SGLT2 inhibitors is much better established now. We know about those common factors in terms of concurrent illness, dehydration, low carbohydrate intake, that increases the risk of somebody developing diabetic ketoacidosis.

So these latest guidelines have updated the range of scenarios where you might think about stopping it. These guidelines discuss the importance of counselling your patients about sick day management, and also what they should do before a procedure. So a key point is that, if a patient's acutely unwell, we should be [with]holding the SGLT2 inhibitor, and the patient themselves should know to do that. But also, if a patient’s undergoing a procedure such as surgery, or requiring bowel prep prior to a colonoscopy, then they need to be stopping the SGLT2 inhibitor. The guidelines suggest stopping at 3 days before a procedure, which is usually 2 days before the bowel prep and the day of the procedure itself. And we shouldn't be restarting these until a patient is eating and drinking well, and back to their normal state of health.

Thank you, Tilenka Thynne. Just to finish on something a bit more quirky, but of interest to you and I, because we write a fair bit about diabetes. Looking at the language of diabetes, it does occur to me that perhaps you and I on this very podcast have not been entirely correct with all our language. But in particular, we're trying to move away from terms such as glucose control and replace those with glycaemic management, which people would hardly notice when they read these guidelines. But you've just been to the national conference, and they were talking about this sort of thing as well.

I think language is important. And it might seem like a small thing, but Diabetes Australia was really ahead of the game when it started talking about this with a position statement on the use of language around diabetes way back in 2011, and that has been really widely adopted worldwide. I think it's important when we think about using terms such as glycaemic control, or a diabetic, and poor control, there's a lot of labelling that goes into that. And we lose sight of an individual patient, and what their own goals and desires and abilities, and what their wants are.

I've just been to the Australian Diabetes Congress here in Adelaide at the end of August, and there was a fantastic session which addressed the issue of diabetes stigma. On upcoming World Diabetes Day, there's a launch of an international consensus and pledge to eliminate diabetes stigma, which I think is a really exciting concept, and one that's going to be multifactorial in terms of how we approach it. The way we label things and the language we use really does matter, and I think it really sets the tone to how we think about the management of diabetes.

I think that's a wonderfully positive and futuristic note to end on. Thanks very much, Tilenka Thynne, for lending us your wisdom on this Australian Prescriber podcast.

Thanks, Justin.

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My guests' views are their own, and don't represent Australian Prescriber, and my views are certainly all mine. [Dr Tilenka Thynne is a member of the Australian Prescriber Editorial Executive Committee]