Diabetes guidelines in Practice-clinical case 2

My name is Fernando Florido and I am a GP in the United Kingdom. In today’s episode I look at a new random case to see how the guidelines could apply to it. By way of disclaimer, I am not giving medical advice; this video is intended for health care professionals and 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.

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

·      The NICE GP YouTube Channel: NICE GP - YouTube

This podcast also appears in:

 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

Prescribing information links:

·      Website: DPP-4 inhibitors | Prescribing information | Diabetes - type 2 | CKS | NICE or

·      Download PDF: DPP-4 inhibitors- Prescribing information- Diabetes- type 2- NICE.pdf

·      Website: GLP-1 receptor agonists | Prescribing information | Diabetes - type 2 | CKS | NICE or

·      Download PDF: GLP-1 receptor agonists- Prescribing information- Diabetes- type 2- NICE.pdf

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Transcript

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

In today’s episode I look at a new random diabetic case to see how the guidelines could apply to it. By way of disclaimer, I am not giving medical advice; see the description for full information about this:

·     NOT medical advice

·     Intended for health care professionals

·     Only my interpretation of the guideline

·     Use your clinical judgement

And as you know, we are focusing only on the pharmacological treatment.

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 generate our random patient. So, we have 45-year-old woman with poorly controlled T2DM with an HbA1c of 60 mmols/mol/7.6%, who has CKD stage 3a with an eGFR of 45 and who is also at high risk of CVD. She is also on triple therapy with Metformin 500 mg BD, Dapagliflozin 10 mg OD and Saxagliptin 2.5mg OD. And finally, she is severely obese with a BMI of 43

So, let’s have a look at the guidelines. As usual I will focus on the NICE guidelines but at the end I will tell you what my interpretation would have been following the EASD / ADA consensus guideline.

Firstly NICE says that we need to consider if rescue therapy is necessary for symptomatic hyperglycaemia with insulin or a sulfonylurea.

And for the clinical presentation we will say that she has no symptoms of diabetes, her obesity is long-standing and being managed with diet, lifestyle advice and bariatric referral. We have excluded other causes of Obesity e.g. hypothyroidism or Cushing’s disease and, because of her age, other causes of CKD such as glomerulonephritis or obstructive nephropathy have also been excluded and she has the diagnosis of diabetic nephropathy.

Right, so what are my thoughts? Firstly, that she is relatively young and she already has a degree of diabetic nephropathy. So we should manage her fairly aggressively to try and improve her diabetic control and improve long term outcomes.

Secondly, it seems quite clear that her main problem is her weight. She is severely obese and already being managed for that. I am very pleased to see that she is not on any medication that promotes weight gain. Both metformin and SGLT2 inhibitors promote weight loss and DPP4 inhibitors are weight neutral. So Dr Spinning Wheel has done very well indeed.

The first step is always metformin which would be helpful for her weight too. So I would be interested to see why she is only on 500mg BD instead of the full dose, double that, 1000mg BD.

I would first look if it has been kept at that dose because of safety reasons, for example because of her renal function. You can prescribe metformin 1000 mg BD to anyone with an eGFR of 45 or above. Her eGFR is exactly that, 45. Because of being right on the limit, I would want to be sure and I would look back and see what her previous renal function tests have been. If previously the eGFR has been bumping along the high 40s or 50s that I would definitely increase the dose because the drop to 45 could be just a temporary “blip”, although, of course, we would watch her renal function closely. If on the other hand her previous eGFR readings have been in the high 30s or low 40s, then I would not increase the dose because I would want to see a stable eGFR above 45 before increasing it. 

If she is suitable for a dose increase, I would also like to look at previous records and see if she has not tolerated higher doses. And if that is the case, I would also want to make sure that she has been managed appropriately. NICE says that metformin should be increased gradually over several weeks to minimise the risk of gastrointestinal side effects. So, if the previous increase in dose was abrupt, I would want to revisit it. Also I would make sure that the patient is counselled and advised that for many patients the side effects are temporary and get better over a number of weeks. So, I would advise her that, if the side effects are not severe, to try and work through them to see if the short term inconvenience of the side effects can translate into a long term therapeutic benefit. And finally, if she has not been able to tolerate it despite these efforts. NICE says that we should consider a trial of modified‑release metformin, so I would offer this to her too. So I am really emphasizing that we should leave no stone unturned before giving up of the benefits of a full dose of metformin, especially in a person with such an obesity problem.

So, let’s assume that she is keen and able to increase the dose, so we do that. Would I try to add or increase other medication in this consultation too?

Because I want to manage her aggressively and all her medication has a very low risk of hypoglycaemia, I would say yes. True, we may advise her to delay the addition or the increase of other drugs for a few days or weeks to make sure that if side effects develop, we know which medication is the culprit. But as soon as that patient is sure that the increased dose of metformin is not causing any issues, I would add or increase the other medication. I would not want to leave her for, say, 3 months before further action is taken.

So as a next step, NICE says that, for patients at high risk of CVD, we need to consider an SGLT2 inhibitor with proven cardiovascular benefit. And she is on the full dose of dapagliflozin, which is one of them. The cardiovascular benefit of SGLT2 inhibitors is a drug class effect so there isn’t necessarily any need to consider other types if there is no concern with the use of dapagliflozin. Dapagliflozin can be initiated as long as the eGFR is above 15 so her eGFR of 45 is not a problem.

So, we now look at the third drug, which is a DPP4 inhibitor, saxagliptin 25mg OD. NICE says that for patients who are not controlled with dual therapy with metformin and an SGLT2 inhibitor, we should consider either:

u triple therapy, including combinations with either a sulphonylurea or a DPP‑4 inhibitor or,

u going directly from dual therapy to starting insulin

I am definitely going to exclude insulin and a sulphonylurea at this stage because they can be associated with weight gain, which is the last thing that we want for this patient. As we have seen, DPP4 inhibitors are acceptable and saxagliptin is already prescribed. NICE says that the recommended dose of saxagliptin is 5 mg OD and the patient is only on 2.5mg OD. However, the dose of saxaglitpin has to be reduced to 2.5 mg OD if the eGFR is below 45. So, we are in the same situation as the metformin earlier. If her eGFR has consistently been above 45 you can increase the dose but not otherwise.

There are many other considerations when choosing which DPPG4 inhibitor you are going to use and they all have different thresholds for renal impairment, and also other conditions like hepatic impairment, heart failure and for the elderly. So I would encourage you to look at your formulary carefully before making the decision. I will put in the episode description the link for the NICE guidance on DPP4 inhibitor prescribing in case that you are interested.

DPP-4 inhibitors | Prescribing information | Diabetes - type 2 | CKS | NICE

It is worth saying that linagliptin is the only DPP4 inhibitor that does not require dose adjustment for renal or hepatic impairment so if there is any doubt, you can always give linagliptin at the full recommended dose of 5 mg OD.

So this is my interpretation for this patient following the NICE guidelines:

1- increase metformin if at all possible,

2- continue dapagliflozin at the full dose and

3- increase the dose of saxagliptin to 5 mg OD if renal function allows or switch it to linagliptin 5mg OD if there are concerns

What would I do if I were following the EASD / ADA consensus guideline?

Well, I would still try to increase metformin if at all possible and then, because this patient has a high CVD risk, she would be started on a GLP1 receptor agonist for their cardiovascular benefit, independently of the HbA1c level. This would also have the benefit of their added weight loss so that would be great for this patient too.

The difference is that NICE is more restrictive when it comes to GLP1 receptor agonists and they would only be considered if the initial suggestion that I said earlier failed to control the patient.

You can prescribe all of the GLP1 receptor agonists, as long as the eGFR is above 30, so not a real issue for this patient. I will put in the episode description a link to the guidance for the prescribing of GLP1 agonist so have a look if you are interested.

GLP-1 receptor agonists | Prescribing information | Diabetes - type 2 | CKS | NICE

Acceptable options would be:

• exenatide
• liraglutide
• lixisenatide
• dulaglutide or
• semaglutide

The next step after Metformin and GLP1 receptor agonist according to EASD and ADA is an SGLT2 inhibitor.

So my interpretation for this patient following the EASD /ADA guidelines is:

1- increase metformin, if at all possible,

2- stop saxagliptin and start a daily preparation of a GLP1 receptor agonist and

3- continue dapagliflozin at the full dose

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