Diabetes guidelines in Practice-case 1

My name is Fernando Florido and I am a GP in the United Kingdom. With this episode I am starting a new series on Diabetes Guidelines in Practice, looking at how the guidelines could apply to randomly selected clinical cases. By way of disclaimer, remember that guidelines are there to be interpreted and applied using your clinical judgement. What I am doing here is sharing with you what my interpretation would be in this case. It does not mean that it is the only way, or indeed the best way to treat any individual patient. 

This episode also appears in the Primary Care guidelines podcast: 

·      Redcircle: https://redcircle.com/shows/primary-care-guidelines

·      Spotify: https://open.spotify.com/show/5BmqS0Ol16oQ7Kr1WYzupK

·      Apple podcasts: https://podcasts.apple.com/gb/podcast/primary-care-guidelines/id1608821148

 There is a YouTube version of this and other videos that you can access here: 

·      The NICE GP YouTube Channel: NICE GP - YouTube 

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Transcript

Hello everyone and welcome. My name is Fernando Florido and I am a GP in the United Kingdom.

With today’s episode I am starting a new series on Diabetes Guidelines in Practice, looking at how the guidelines could apply to randomly selected clinical cases. By way of disclaimer, remember that guidelines are there to be interpreted and applied using your clinical judgement. I am not giving medical advice here and what I am only doing is sharing with you what my interpretation of the guideline would be in this case. It does not mean that it is the only way, or indeed the best way to treat any individual patient. So, you must always apply your clinical judgement at all times.

 I will also say that I will only focus on the pharmacological treatment of type 2 diabetes. By all means, we will need to advise about diet, exercise, lifestyle etc, but this will not be addressed in these episodes.

Remember that there is also a podcast version of these videos so have a look in the description below.

Remember that there is also a Youtube version of these episodes so have a look in the episode description.

Right, so let’s get started and let’s generate our random patient. For that we are going to spin a random wheel: 

Right, so we have an 85-year-old man, newly diagnosed with type 2 diabetes who is poorly controlled with an HbA1c of 65 mmols or 8.1%, who also has heart failure and CKD stage 3b with an eGFR of 32. In addition, he is underweight, even possibly malnourished to some degree. 

Right, we are going to look at the guidelines and how to apply them. Although I will focus on the NICE guideline, in this case my interpretation and the outcome would be exactly the same if you follow the EASD recommendations or the ADA guideline.

So, what does NICE say that we should do? Firstly, we need to consider if rescue therapy is necessary because, for symptomatic hyperglycaemia, we will need to consider insulin or a sulfonylurea and review when blood glucose control has been achieved. 

So, we are going to assume that he is well and that he has no symptoms of diabetes. He is underweight, but this has been like this for a few years. There hasn’t been rapid weight loss indicating an urgent need for insulin and his urinary ketones are negative. Other causes of unintentional weight loss such as cancer have also been excluded.

So, we are just focusing on the diabetes. His HbA1c is high and has not improved with diet and lifestyle advice, so we should do something. However, given his age, we are not going to manage him too aggressively because, at 85, we are probably more concerned about harmful hypoglycaemia. But he does need treatment and certain diabetic agents could also help his co-morbidities. 

So, next, we must look at his medical history. He has both CKD and heart failure and we know that SGLT2 inhibitors can be beneficial for both these conditions.

However, because of the benefits of metformin, NICE says that first, we should consider starting metformin alone to assess tolerability and once this has been confirmed, we could add an SGLT2 inhibitor.

Arguments against using metformin at all in this patient are that his eGFR is fairly low and at 32 he is quite close to CKD stage 4.

Also, because he is underweight with possible low muscle mass, we need to remember how the estimated GFR is calculated and consider that, as a result of the low muscle mass, his eGFR may be overestimated and that his actual GFR could be below 30. We know that we can use metformin quite normally if the eGFR is above 45, we need to review the dose and prescribe it cautiously if the eGFR is between 30 and 45 and then stop it completely when the eGFR falls below 30.

The manufacturer of metformin also advises caution in chronic stable heart failure with the advice to monitor cardiac function closely.

We also know that metformin can have potential gastrointestinal side effects and promote weight loss, which we would not want in this patient.

And finally, the mode of action of metformin is primarily by reducing insulin resistance. But in an 85-year-old underweight patient, it is more likely that his diabetes is due to insufficient insulin secretion by the ageing pancreas.

On the other hand, we also know that metformin has proved to have cardiovascular benefits.

So, a controversial decision. You could justify both giving and not giving metformin based on this patient’s individual circumstances.

Right, time to decide. What would I do?

I would probably err on the side of caution and not give metformin. It can always be introduced later if his weight goes up and his renal and heart failure are stable or improve with other medication.

If you really wanted to prescribe metformin, it would be best to start a very cautious introduction, maybe at 500 mg OD and then monitoring this patient very closely. Generally, the maximum accepted dose of metformin for patients with an eGFR between 30 and 45 is 500 mg twice daily but I would be quite nervous about it and I would not increase the dose above 500mg OD for this patient unless the circumstances really changed.

So, we are not giving metformin but we still need to prescribe something for this patient. And NICE says that if there is a history of heart failure, we should give an SGLT2 inhibitor with proven cardiovascular benefit. NICE says that the benefits in reduction of hospitalisations for heart failure and cardiovascular mortality can be attributed to SGLT2 inhibitors as a drug class, although at present ertuglifozin has not consistently shown these cardiovascular benefits in clinical trials. So, we are likely to choose either dapaglifozin, canaglifozin or empaglifozin for this patient.

Remember that SGLT2 inhibitors are also associated with possible weight loss, so along with this prescription there should be appropriate nutritional advice.

We also know that there may be an increased risk of DKA associated with SGLT2 inhibitors so NICE advises us that before prescribing, we should check the patient’s individual risk of DKA, for example if, they have had a previous episode of DKA, they are unwell with intercurrent illness or they are following a very low carbohydrate or ketogenic diet. In particular, I would be very keen to make sure that this patient does not continue to lose weight as this is also likely to put him at greater risk of DKA once the SGLT2 inhibitor is started.

Also remember that we will need to check our formulary or BNF if you are in the UK because each drug has its own recommendations and eGFR thresholds for dose reduction, caution or avoid. Acceptable options would be:

·     dapaglifozin maybe starting cautiously at 5 mg OD possibly increasing to 10 mg OD if no issues develop.

·     canaglifozin starting at 100mg OD, which is the starting dose and also the maximum daily dose for anyone with eGFR <60 or

·     empaglifozin starting at 10 mg OD, which is also the starting dose and the maximum daily dose for anyone with eGFR <60

So that would probably be my first pharmacological action for this patient, but by no means is necessarily the only or best one.

Remember that we need to keep monitoring the patient and consider other treatments as and when the situation changes. 

We have come to the end of this episode. I hope that you have found it useful. Thank you for listening and good-bye