From AI to Reality: Navigating Multimorbidity in diabetes with NICE Guidelines
Tuesday, October 17, 2023 • Duration 11:59
This episode makes reference to guidelines produced by the "National Institute for Health and Clinical Excellence" in the UK, also referred to as "NICE". Please note that the content on this channel reflects my professional interpretation/summary of the guidance and that I am in no way affiliated with, employed by or funded/sponsored by NICE.
My name is Fernando Florido and I am a GP in the United Kingdom. In today’s episode I look at a fictitious clinical case of a patient created by Chat GPT to see how the NICE guidelines could apply to it.
I am not giving medical advice; this video is intended for health care professionals, it is only my interpretation of the guidelines and you must use your clinical judgement.
There is a YouTube version of this and other videos that you can access here:
There is a YouTube version of this and other videos that you can access here:
The patient was created using the following Chat GPT prompt:
A) Provide a fictitious patient. Details that you should include are:
1) patient's medical information including:
· name
· age
· sex
· ethnicity
· BMI
· blood pressure
2) medical history- you must include:
· either one or two of the following poorly controlled conditions:
· type 2 diabetes
· hypertension
· dyslipidaemia,
· Asthma or COPD
· Any number of other medical conditions of your choice, along with whether they are well controlled or not – the medication for these conditions should appear in the next section “medications”
Medications given:
· indicate whether the patient is currently taking medication for each medical condition or not.
· If medication is prescribed for a condition, indicate the specific drug(s) and their dosages. You may choose to prescribe one, two, or three drugs for each condition as appropriate.
3) State whether the patient tolerates the medication well or not, and if not, describe the side effect(s) and their severity.
4) blood test results (give a bulleted list but do not number them):
· HbA1c expressed in % and mmol/mol
· renal function tests to include creatinine (expressed first in µmol/L and then in mg/dL), eGFR, urea, sodium, and potassium (expressed in UK units first and then USA units)
· lipid profile expressed both in mmol/L first and then in mg/dL.
· If the patient has asthma, give the peak flow reading expressed as a percentage of their best or expected reading.
· If the patient has COPD, give the FEV1 reading expressed as a percentage of the predicted reading
· include any other relevant test results for the patient, expressing them in both UK and USA units. If the patient has hypothyroidism or takes levothyroxine medication, provide the results of their thyroid function tests, including both T4 and TSH levels, in both UK and USA units. Also, include the normal range for these investigations.
B) Provide the patient's cardiovascular risk using the QRISK2 tool, calculated as a percentage of the likelihood of experiencing a cardiovascular event over the next 10 years.
C) At the end of the patient information, ask: 'What treatment recommendations would you make?' – do not make recommendations yourself
D) Do not include a disclaimer that the patient is fictitious.
The NICE hypertension flowcharts can be found here:
· Image by Freepik: Image by a href="https://www.freepik.com/free-photo/excited-young-friends-running-beach_9057871.htm#page=2&query=45%20year%20old%20obese%20woman&position=10&from_view=search&track=ais"Freepik/a
Intro / outro music: Track: Halfway Through — Broke In Summer [Audio Library Release]
Hello everyone. My name is Fernando and I am a GP in the United Kingdom. Today we are looking at a fictitious patient generated by Chat GPT with a view to looking at the NICE guidelines from a practical perspective.
If you would like to know the Chat GPT prompt that I have used, you can find it in the episode description.
Right, so let’s jump into it.
Patient Information:
· Name: Sarah Davis
· Age: 45
· Sex: Female
· Ethnicity: Caucasian
Examination:
· BMI: 32 (Obese)
· Blood Pressure: 153/91 mm Hg
Medical History:
· Type 2 Diabetes
· Hypertension
· Dyslipidemia
· Asthma
· Obesity
· Depression
Medications:
· Metformin 1000 mg twice daily
· Gliclazide 80 mg once daily
· Amlodipine 10 mg once daily
· Indapamide MR 1.5 mg once daily
· Atorvastatin 20 mg once daily
· Salbutamol inhaler as needed
· Sertraline 50 mg once daily
Medication Tolerance:
· Sarah tolerates her medications well. She has not reported any significant side effects.
Blood Test Results:
· HbA1c: 8.5% (69 mmol/mol)
· Renal Function:
o Creatinine: 90 µmol/L (1.02 mg/dL)
o eGFR: 91 mL/min/1.73m²
· Lipid Profile:
o Total Cholesterol: 5.2 mmol/L (200 mg/dL)
o LDL Cholesterol: 3.0 mmol/L (116 mg/dL)
o HDL Cholesterol: 1.2 mmol/L (46 mg/dL)
o Triglycerides: 2.5 mmol/L (220 mg/dL)
Cardiovascular Risk (QRISK3):
· Sarah's 10-year cardiovascular risk is estimated at 18%.
So, what treatment recommendations would we make?
Although there is a lot that we can do from a lifestyle perspective, we will focus on the drug treatment only.
Right, let’s start with her diabetes, which is poorly controlled with an hba1c of 8.9% or 74 mmol/mol. Sarah is on metformin 1gr BD and gliclazide 80 mg OD and we know she is at high risk of cardiovascular disease with a QRISK3 of 18%.
NICE says that for step 2 treatment after metformin, if a patient is at high risk of CVD, we should choose an SGLT2 inhibitor. But this patient has been given gliclazide instead. We would like to see if there is a reason for this and whether an SGLT2 inhibitor was tried before but not tolerated.
So, assuming that there have been no issues, I would recommend starting an SGLT2 inhibitor.
SGLT2 inhibitors are also associated with a degree of weight loss, and given that Sarah is obese, this will be good for her.
Gliclazide on the other hand is associated with weight gain, which is the last thing that Sarah needs. The question now is whether we should stop gliclazide and, if so, when.
In my opinion, gliclazide should be definitely stopped and substituted by another diabetic agent which is weight neutral, for example, a DPP4 inhibitor.
A more difficult question would be when to make this switch. Doing it straightaway has got the disadvantage that, if a side effect develops, we may not know which drug is the culprit. Also, we do not know how much the HbA1c will drop with the SGLT2 inhibitor so there could be a risk of overtreatment.
Right, a balanced decision that you can make depending on your clinical judgement.
I think that I would start the SGLT2 inhibitor first, so, I would start her on something like dapagliflozin 5 mg OD initially and, if tolerated, I may increase it to 10 mg daily fairly quickly, possibly within 3 or 4 weeks to get the maximum effect as soon as possible.
Research studies have shown that the introduction of an SGLT2 inhibitor can lead to a drop in Hba1c of around 1%. Although this could vary depending on the individual patient, Sarah’s HbA1c is poor at 8.9% so even after the SGLT2 inhibitor, she is likely to require a third diabetic agent.
NICE says that if dual therapy with metformin and another oral drug is not enough, we should consider either triple therapy by adding a DPP‑4 inhibitor, pioglitazone or a sulfonylurea or starting insulin. Because of the risk of weight gain, I would try to avoid gliclazide and insulin.
Given that she is on gliclazide 80 mg daily, that is, a quarter of the maximum daily dose of gliclazide, I would probably switch Sarah to a DPP4 inhibitor as soon as she is tolerating the full dose of dapagliflozin. So, we could stop gliclazide and start her on, for example, sitagliptin 25mg daily, which is also a quarter of the maximum daily dose of 100mg.
But I do not think that there is a right or wrong approach in terms of the gliclazide switch. The decision about the timing is very dependent on the individual patient and your clinical judgement. Switching early has some more uncertainty about treatment response whereas switching later may mean that the patient remains on a potentially unsuitable drug for longer.
We have to make sure that we inform the patient that SGLT2 inhibitors have been associated with an increased risk of DKA, toe and lower limb amputations and Fournier’s gangrene.
So, on starting the SGLT2 inhibitor:
1. We will educate her about DKA symptoms and when to seek advice.
2. We will also advise against ketogenic diets to lose weight while on an SGLT2 inhibitor, as this also increases the risk of DKA.
3. We will improve foot care and
4. We will advise patients to seek urgent medical advice if they experience pain, erythema or swelling in the genital or perineal area, as this may precede Fournier’s gangrene or necrotising fasciitis.
If we were managing her diabetes according to the European or American guidelines, we would be talking a lot more about GLP 1 receptor agonists, given that they are also recommended for patients with high CVD risk and they are much better in terms of weight loss. We are following the NICE guidelines, which are more restrictive with GLP1 receptor agonists, but we can always use our clinical judgement to deviate from the guideline if we think that it is appropriate for a particular patient.
Now that we have dealt with her diabetes, let’s look at her hypertension.
Unless we have specific concerns, we do not need to arrange an ABPM or HBPM because NICE says that we can use clinic blood pressure measurements to monitor drug treatment for people already diagnosed with hypertension. However, NICE also say that in diabetes, we should check both the sitting and standing BP because of their higher risk of postural hypotension, especially if there is autonomic neuropathy.
Sarah’s BP is 153/91 and NICE says that the target BP for people under the age of 80 is below 140/90. So, her BP is high.
She is on amlodipine and indapamide, which is not in keeping with NICE guidance. NICE says that, for people with diabetes of any age and any ethnicity background, an ACEI or ARB should be used as first line treatment.
So, I would have a look to see if an ACE inhibitor or ARB has been tried before and then stopped because of side effects like a cough or angioedema. Both of these side effects can happen with ACEIs and they are normally managed by switching to an ARB. But, although much rarer, these symptoms can also be a side effect of ARBs
Assuming that there is no previous problem, I would start her on an ACE inhibitor, for example lisinopril 2.5 mg daily monitoring her renal function and titrating up according to response.
If the target BP is achieved at a lower dose than the maximal dose of the ACE inhibitor, then I would recommend stopping indapamide and continue titrating up the ACE inhibitor dose to compensate. Thiazide like diuretics can worsen diabetes so stopping indapamide and replacing it with a higher dose of lisinopril would be the right thing to do.
Once indapamide has been stopped, if the target BP is achieved before the ACE inhibitor is at the maximal dose, we could consider reducing the dose of amlodipine while we increase the ACE inhibitor further, because of the benefits that ACE inhibitors have particularly in diabetes.
Now, let’s look at her hyperlipidaemia. Sarah has no history of cardiovascular disease so she is on atorvastatin 20 mg daily for primary prevention.
NICE says that we should offer atorvastatin 20 mg for the primary prevention of CVD if they have a QRISK score of 10% or more.
After atorvastatin 20mg has been started, and unlike secondary prevention, there are no specific lipid targets in primary prevention but, if we judge the person to be at higher cardiovascular risk, we will consider increasing the dose of atorvastatin in order to achieve a greater than 40% reduction in non‑HDL cholesterol.
In Sarah’s case, both her cholesterol and QRISK3 score are still high on atorvastatin 20 mg, so we could consider her to be at higher risk and, if the 40% drop in non HDL cholesterol has not happened, we could increase atorvastatin to 40 mg and monitor her blood tests.
Let’s now move on to her asthma. Sarah is on step 1 treatment, that is, on-demand Salbutamol inhaler as needed. If Sarah has infrequent symptoms, this is fine, but we should check that she has no symptoms that could indicate the need for maintenance therapy, for example, asthma-related symptoms 3 times a week or more, or symptoms causing waking at night. In that case, we should offer a low dose of an ICS, for example standard beclomethasone 100mcg, one or two inhalations twice daily.
The next issue is Sarah’s depression, for which she takes sertraline 50 mg daily. We don’t know how long she has been taking them for but NICE recommends that SSRIs are taken for at least 6 months (and for some time after symptoms remit). So we should assess how long she has been on it and if she wishes to continue treatment or whether the time has come to consider stopping after a gradual reduction of the dose.
It is worthwhile mentioning that the BNF says that SSRIs should be prescribed with caution in diabetes because SSRIs can affect diabetic control. We are advised to monitor blood glucose when starting or stopping an SSRIs.
Finally, let’s have a look at her obesity. Her BMI is 32. Apart from the obvious dietary and lifestyle changes, NICE recommends a number of pharmacological treatments for obesity such as orlistat, liraglutide and semaglutide. They all have different BMI thresholds and I would advise you to look at the different criteria before prescribing.
Except orlistat, liraglutide and semaglutide can only be given for obesity by a secondary care service. However, as discussed earlier and based on our clinical judgement, we could deviate from the NICE guideline and give a GLP1 receptor agonist for her diabetes instead of an SGLT2 inhibitor.
We have come to the end of this episode. Remember that this is not medical advice and it is only my summary and my interpretation of the guidelines. You must always use your clinical judgement.
Thank you for listening and goodbye.
Real life complex patient: NICE on diabetes, hypertension, hypertriglyceridemia and hypothyroidism
Sunday, July 30, 2023 • Duration 12:57
My name is Fernando Florido and I am a GP in the United Kingdom. In today’s episode I look at a real-life case to demonstrate 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 you must use your clinical judgement.
The PDF version of this episode can be found here:
Intro / outro music: Track: Halfway Through — Broke In Summer [Audio Library Release]
Diabetes in Primary Care UK- Full NICE guideline- Episode 3 of 3
Thursday, May 13, 2021 • Duration 19:15
My name is Fernando Florido and I am a GP in the United Kingdom. In this podcast I go through the NICE Guideline: Type 2 diabetes in adults: management (NG28 guideline). The podcast covers the full NICE guideline, adding additional information from other clinical guidelines when a reference has been made to them.
Links:
NICE Guideline NG28 (Type 2 diabetes in adults) can be found here:
Diabetes in Primary Care UK- Full NICE guideline- Episode 2 of 3
Thursday, May 13, 2021 • Duration 16:51
My name is Fernando Florido and I am a GP in the United Kingdom. In this podcast I go through the NICE Guideline: Type 2 diabetes in adults: management (NG28 guideline). The podcast covers the full NICE guideline, adding additional information from other clinical guidelines when a reference has been made to them.
Links:
NICE Guideline NG28 (Type 2 diabetes in adults) can be found here:
Diabetes in Primary Care UK- Full NICE guideline- Episode 1 of 3
Wednesday, May 12, 2021 • Duration 18:04
Type 2 diabetes in adults NICE guideline -full guideline- Episode 1 of 3
My name is Fernando Florido and I am a GP in the United Kingdom. In this podcast I go through the NICE Guideline: Type 2 diabetes in adults: management (NG28 guideline). The podcast covers the full NICE guideline, adding additional information from other clinical guidelines when a reference has been made to them.
Links:
NICE Guideline NG28 (Type 2 diabetes in adults) can be found here:
Diabetes in Primary Care UK- Type 2 diabetes NICE guideline: Non-insulin drug management of glycaemia
Season 1 · Episode 1
Wednesday, March 24, 2021 • Duration 15:47
My name is Fernando Florido and I am a GP in the United Kingdom. In this podcast I go through the NICE Guideline: Type 2 diabetes in adults: management (NG28 guideline). The podcast focuses in the non-insulin drug treatment recommendations in blood glucose management in adults with Type 2 Diabetes.
The algorithm for blood glucose lowering therapy in adults with type 2 diabetes can be found here: https://www.nice.org.uk/guidance/ng28/resources/algorithm-for-blood-glucose-lowering-therapy-in-adults-with-type-2-diabetes-pdf-2185604173
Intro / outro music by Karveas, provided by YouTube Audio Library.
Chat GPT patient meets NICE: This is what happened!
Friday, April 28, 2023 • Duration 18:32
"Chat GPT Patient Meets NICE - Here's What Happened!"
My name is Fernando Florido and I am a GP in the United Kingdom. In today’s episode I look at a complex random clinical case of a patient created by Chat GPT to see how the NICE guidelines could apply to it. By way of disclaimer, I am not giving medical advice; this podcast is intended for health care professionals, it is only my interpretation of the guidelines and you must use your clinical judgement.
There is a YouTube version of this and other videos that you can access here:
A) Provide a fictitious patient. Details that you should include are:
1) patient's medical information including:
· name
· age
· sex
· ethnicity
· BMI
· blood pressure
2) medical history- you must include:
· either one, two or three of the following poorly controlled conditions:
· type 2 diabetes
· hypertension
· dyslipidaemia,
· Any number of other medical conditions of your choice, along with whether they are well controlled or not – the medication for these conditions should appear in the next section “medications”
Medications given:
· indicate whether the patient is currently taking medication for each medical condition or not.
Diabetes guidelines in Practice-clinical case 2
Saturday, March 18, 2023 • Duration 10:59
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:
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:
My name is Fernando Florido and I am a GP in the United Kingdom. In this podcast I I give my summary of the online course by the EASD learning website “Cardiovascular health and diabetes”.
This podcast will be saved on a website.
There is also a YouTube video on this subject and other NICE guidance. You can access the channel here:
Hello everyone and welcome to the channel. My name is Fernando Florido and I am a GP in the United Kingdom. Today we are going to talk about the link between cardiovascular health and diabetes. The information that I am going to give is based on an online course that is available on the EASD learning website. I highly recommend it and I will put the link to access this course in the episode description. It has seven modules and it is likely to take you between 5 and 7 hours to complete it, depending on how quickly you can process the information. Today’s episode is a summary of the course, which I hope that you will find useful.
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Hello everyone and welcome. My name is Fernando and I am a GP in the United Kingdom.
We have looked at fictitious patients in previous episodes but, in today’s episode, I am going to look at a real diabetic case to see how the guidelines could apply to it. And as you know, we are focusing only on the pharmacological treatment. If you want to download a PDF version of this episode, the link is in the episode description.
Please note that I am not giving medical advice; this is only my interpretation of the guidelines and you must use your clinical judgement
Remember that there is also a Youtube version of these episodes so have a look in the episode description.
Right, so let’s get straight into it. The details, which have been anonymised, belong to a real patient, so we have 46-year-old man of Asian descent with T2DM who presents with the following:
HbA1c is 68 mmols/mol/8.4% (therefore poorly controlled)
Cholesterol 5.9
Triglycerides 5.72
HDL 0.97
· The path lab has not calculated LDL because triglycerides >4.5
· Liver and Renal function tests are normal with an eGFR of 97
Thyroid function tests show a borderline low T4 of 9 (NR 9-19.1) and a raised TSH of 9.88 (NR 0.35-4.94
ACR normal
FBC and other routine blood tests were normal.
His BMI is 32, so he is obese
His BP is 147/89
His PMH includes:
Hypothyroidism
T2DM
His regular treatment is with:
Levothyroxine 200mcg daily
Metformin 500 mg TDS
He comes to discuss his test results, feeling well in himself. His obesity is long-standing and being managed with diet and lifestyle advice. He has had hypothyroidism for 15 years and, on prompting, he says that he is feeling a little tired
So, let’s have a look at the guidelines. As usual I will focus on the NICE guidelines and we will have to looks at the guidelines on type 2 diabetes, hypertension, prevention of cardiovascular disease, and hypothyroidism
Let’s look at his diabetes first.
Firstly, NICE says that we need to consider if rescue therapy is necessary for symptomatic hyperglycaemia with insulin or a sulfonylurea. However, he is well and asymptomatic so we do not have to do this.
We see that his current dose of metformin 500 mg 3 times a day is not enough to control his diabetes. So, given that his renal function is completely normal. we should increase the dose to the maximum of 2000mg daily, that is, 1000mg twice a day. However, this is unlikely to be enough to bring his HbA1c of 68 or 8.4% to target. And let’s remember that according to NICE we should strive for the following targets:
· Lifestyle management only— 48 mmol/mol (6.5%).
· A single drug not associated with hypoglycaemia (such as metformin) — 48 mmol/mol (6.5%).
· Drug treatment associated with hypoglycaemia (such as a sulfonylurea): 53 mmol/mol (7.0%).
· Always adjust for people who are frail, elderly or with other co-morbidities
This patient is young and otherwise well so we should aim to treat him aggressively.
NICE says that for people not controlled on metformin alone, we should consider dual therapy but which?
We need to assess the person's cardiovascular status and risk to determine whether they have chronic heart failure, established atherosclerotic cardiovascular disease, or are at high risk of developing cardiovascular disease.
This patient does not have heart failure or cardiovascular disease but using an online calculator, his 10-year QRISK3 score is 12%. So, being over 10%, we will consider him at high risk of developing CVD.
And NICE says that if the patient is at high risk of developing cardiovascular disease, we will consider an SGLT-2 inhibitor with proven cardiovascular benefit in addition to metformin.
This is good because it seems quite clear that his obesity is a problem and both metformin and SGLT2 inhibitors promote weight loss.
Because we would want to manage him aggressively, I would advise him to increase metformin straightaway and as soon as we know that it is tolerated, which could be a matter of days, we could start the SGLT2 inhibitor.
SGLT2 inhibitors with proven cardiovascular benefit includes dapagliflozin, empagliflozin and canagliflozin
Remember that SGLT2 inhibitors are associated with an increased risk of DKA and lower limb amputation. Therefore, before starting an SGLT2 inhibitor, we need to check whether the person may be at increased risk of diabetic ketoacidosis (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, and if so, not to start the SGLT2 inhibitor until they have changed their diet. We will also advise them not to start this type of diet while they are on this medication.
The increased risk of lower-limb amputation has been shown with Canagliflozin but there is some concern that the risk may be a class effect. We will need to ensure that foot care is optimised before starting the SGLT2 inhibitor.
So, this would be my pharmacological action from a diabetic perspective. Increase metformin to 1000mg BD and start an SLGT2 inhibitor, for example, dapagliflozin 10 mg OD.
Now let’s have a look at his BP, which is elevated at 147/89.
NICE says that people under the age of 80 should have a BP below 140/90.
To confirm the diagnosis, we should arrange ambulatory or home blood pressure monitoring and if the average is greater than 135/85 we will start him on antihypertensive treatment. We have more or less established that he does not have end-organ damage because of his normal renal function, normal urinary albumin / creatinine ratio and, looking at his records, normal fundoscopy, as he attends for his annual diabetic retinal screening programme. To be strict, we should also arrange an ECG to ensure that there are no signs of left ventricular hypertrophy.
Let’s assume that his BP is indeed above the target. What treatment should we start?
NICE says that for someone with diabetes of any ethnicity and any age, we should start and ACEI or ARB. We know that ACEI confer significant renal protection in diabetes, so we will start him on an ACEI, something like lisinopril 2.5 mg daily, monitoring his renal function and increasing the dose gradually according to our clinical judgement. This patient is of Asian family background but remember that if the patient is of Afro-Caribbean family origin, we should opt for an ARB in preference to an ACEI. This is because Afro-Caribbean patients are considered “low renin responders” and therefore ACEI are less effective in this group.
Now let’s look at his lipids and what we would do based on the NICE guideline on prevention of cardiovascular disease.
Firstly, we will calculate his CV risk.Using the online QRISK3 calculator we find that his 10-year risk is 12% Further details are:
Your 10-year QRISK®3 score 12%
The score of a healthy person with the same age, sex, and ethnicity 2.6%
Relative risk** 4.6
Your QRISK®3 Healthy Heart Age 66
But remember that NICE also says that the CVD risk may be underestimated by risk assessment tools if the triglyceride levels are raised, which is this patient’s case.
Could this be treated with lifestyle alone? Because we need to treat him aggressively, I would say no. Furthermore, his cholesterol has been elevated well over 5 mmol/l (200 mg/dL) for the last 3 years so it is clear that diet and exercise alone are not doing the job.
NICE says that for Primary prevention:
If lifestyle modification is ineffective or inappropriate, we will offer a statin, generally atorvastatin 20 mg, for the primary prevention of CVD to people who have a 10% or greater 10‑year CVD risk using the QRISK assessment tool.
For people 85 years or older we will still consider atorvastatin 20 mg as statins may be of benefit in reducing the risk of non‑fatal MI.
Should we do anything different from the point of view of his triglycerides?
Well, first of all, we will look to see if they have been this high for long. Previous entries show levels moderately elevated but not to this degree.
Triglycerides are also affected by diabetes control and it may very well be that once his hyperglycaemia improves, and his HbA1c goes down, his triglycerides will too.
Triglycerides may be also elevated in situations where excess alcohol is consumed. So, we should enquire about this.
And hypothyroidism can also influence lipids in general and triglycerides in particular. Improving his hypothyroidism treatment is also likely to improve the lipid situation.
Also, atorvastatin will have some effect on the triglycerides, although this effect may not be very pronounced.
Other drugs like fibrates, such as fenofibrate, are potent agents in reducing triglyceride levels. However, NICE do not recommend their use. In fact, NICE says that:
For the prevention of CVD, we should not offer Fibrates, Nicotinic acid, Bile acid sequestrants or Omega‑3 fatty acid compounds, either alone or in combination therapy.
In summary, I would start him on atorvastatin 20 mg daily and recheck his liver tests and lipids 3 months later, perhaps on a fasting sample, to see if the triglycerides have improved too. Remember that we aim for a greater than 40% reduction in non‑HDL cholesterol and, if this target is not achieved, we will consider increasing the dose.
And finally, what about his hypothyroidism? He has had it for some time and is on a dose of 200 mcg daily of levothyroxine but his T4 is still on the low side and his TSH is elevated. And he also complains of being tired at times.
In terms of management of hypothyroidism, NICE says that we should adjust the dose according to symptoms and TFT results, aiming to maintain TSH and T4 levels to within or close to the normal reference range. We should also review the person and recheck TSH levels every 3 months after every dose change.
The BNF says that for adults under 50 the dose adjustments would be in steps of 25–50 micrograms every 3–4 weeks, according to response. However, a little fly in the ointment is that the BNF recommends the maintenance dose to be up to 200 micrograms once daily. And this is precisely this patient’s dose.
Sometimes patients do need higher doses but, perhaps we should discuss compliance with him given that it may very well be that he is not taking it regularly and this is why his tests results are not in the normal range.
Right, so this would be my initial management of this real-life patient: more metformin, dapagliflozin, lisinopril, Atorvastatin and discuss if increasing Levothyroxine is necessary. Remember that this is only my interpretation of the guidelines.
We have come to the end of this episode. I hope that you have found it useful. Thank you for listening and good-bye
Intro / outro music by Karveas, provided by YouTube Audio Library.
· If medication is prescribed for a condition, indicate the specific drug(s) and their dosages. You may choose to prescribe one, two, or three drugs for each condition as appropriate.
3) State whether the patient tolerates the medication well or not, and if not, describe the side effect(s) and their severity.
4) blood test results (give a bulleted list but do not number them):
· HbA1c expressed in % and mmol/mol
· renal function tests to include creatinine (expressed first in µmol/L and then in mg/dL), eGFR, urea, sodium, and potassium (expressed in UK units first and then USA units)
· lipid profile expressed both in mmol/L first and then in mg/dL.
· include any other relevant test results for the patient, expressing them in both UK and USA units. If the patient has hypothyroidism or takes levothyroxine medication, provide the results of their thyroid function tests, including both T4 and TSH levels, in both UK and USA units. Also, include the normal range for these investigations.
B) Provide the patient's cardiovascular risk using the QRISK2 tool, calculated as a percentage of the likelihood of experiencing a cardiovascular event over the next 10 years.
C) At the end of the patient information, ask: 'What treatment recommendations would you make?' – do not make recommendations yourself
D) Do not include a disclaimer that the patient is fictitious.
The NICE hypertension flowcharts can be found here:
Today we'll be exploring the world of NICE guidelines and how they apply to a complex patient. But this isn't just any patient - this one was randomly created by the latest buzz in town, ChatGPT. Our focus will be on the pharmacological treatment.
Hello and welcome, I'm Fernando Florido, a GP in the United Kingdom.
Before we dive in, I'd like to make it clear that I'm not here to provide medical advice. Rather, I'll be sharing my interpretation of the guidelines with fellow healthcare professionals. Please always use your clinical judgement when treating your patients.
If you prefer a video format, we've also got a YouTube version of these episodes. The link is in the episode description.
Alright, let's generate our patient using ChatGPT. It was created using a specific prompt, which is available in the episode description. Let's get started!
Right, so our fictitious patient is Sarah Johnson, a 52-year-old African American woman. Sarah is currently obese with a BMI of 31, and her Blood Pressure is above the target at 142/88 mmHg.
She has a Medical History of
Type 2 diabetes and Hypertension, which are both poorly controlled as well as
Osteoarthritis (which is well-controlled with ibuprofen)
Asthma (which is well-controlled with salbutamol inhaler) and
Depression (which is well-controlled with fluoxetine)
Her regular Medications are:
Metformin 1000 mg twice a day for diabetes
Lisinopril 20 mg once a day for hypertension
Atorvastatin 40 mg once a day for dyslipidaemia
Ibuprofen 400 mg twice a day for osteoarthritis
Salbutamol inhaler 2 puffs as needed for asthma
Fluoxetine 20 mg once a day for depression
Fortunately, she tolerates all medications well without any side effects.
We also have her blood test results, which show the following:
An HbA1c: 8.5% (69 mmol/mol)
A Creatinine: 94 µmol/L (1.06 mg/dL)
· An eGFR: 72 mL/min/1.73m2
(Urea: 5.2 mmol/L (14.67 mg/dL)
Sodium: 139 mmol/L (139 mEq/L)
Potassium: 4.2 mmol/L (4.2 mEq/L))
· A Total Cholesterol: 6.1 mmol/L (236.39 mg/dL)
(HDL Cholesterol: 1.3 mmol/L (50.1 mg/dL))
· And an LDL Cholesterol: 4.1 mmol/L (158.57 mg/dL)
(Triglycerides: 1.8 mmol/L (159.27 mg/dL)
TSH: 2.5 mIU/L , 2.5 µIU/mL
Free T4: 15 pmol/L, 1.2 ng/dL
Normal TSH range: 0.4-4.0 mIU/L , 0.4-4.0 µIU/mL
Normal Free T4 range: 9-25 pmol/L , 0.8-2.0 ng/dL )
Finally, Sarah's QRISK2 score is 20%, indicating a high risk of developing cardiovascular disease over the next 10 years.
Based on Sarah's medical history, blood test results, and QRISK2 score, I would recommend the following treatment options.
Upon initial examination, this 52-year-old woman presents with a significant amount of multimorbidity, including diabetes, hypertension, dyslipidaemia, osteoarthritis, asthma, and depression. Her obesity is likely exacerbating her conditions, particularly her diabetes, hypertension, and osteoarthritis, and may also be contributing to her depression. Given this, tackling her obesity could potentially have a positive impact on her overall health. However, for the purpose of this case, we will focus on the pharmacological treatment rather than lifestyle interventions.
It is worth noting that the patient's eGFR of 72 indicates stage 2 CKD, which will factor into our treatment decisions. We will assume that there is no significant microalbuminuria since ACR results are not available. Additionally, the patient has a high risk of CVD, so managing her conditions aggressively will also help mitigate this risk.
Moving on to her poorly controlled diabetes, which is currently being treated with metformin 1gr BD and has an HbA1c of 8.5% or 69 mmol/mol, NICE guidelines recommend an SGLT2 inhibitor as step 2 treatment after metformin for patients at high risk of CVD. SGLT2 inhibitors are also beneficial for those with CKD and can promote weight loss, so a good option for this patient. In this case, starting the patient on dapagliflozin 5mg OD initially, and potentially increasing to 10mg daily within four weeks if well-tolerated, would be a suitable option.
It is important to note that SGLT2 inhibitors have been associated with an increased risk of DKA, toe and lower limb amputations, and Fournier's gangrene.
Fournier’s gangrene is a rare but life-threatening type of necrotizing fasciitis, which specifically affects the genital and perineal area. The condition develops rapidly, and symptoms may include fever, severe pain, redness, swelling, and foul-smelling discharge in the affected area. The infection can spread quickly and cause significant tissue damage, leading to sepsis, shock, and organ failure if not treated promptly.
Therefore, it is crucial to educate the patient on DKA symptoms, advise against starting a ketogenic diet while taking an SGLT2 inhibitor, as this increases the risk of DKA, and promote excellent foot care. Additionally, we should advise the patient to seek urgent medical advice if they experience severe pain, erythema, or swelling in the genital or perineal area, especially if there is fever or malaise, as urogenital infection or perineal abscess may precede necrotising fasciitis.
While GLP-1 receptor agonists would be recommended for patients with high CVD risk following the European and American guidelines, the NICE guidelines are more restrictive in this respect. However, an SGLT2 inhibitor is still an effective and straightforward option for this patient.
Now that we have addressed her diabetes, let's move on to her hypertension.
We'll be treating our patient's clinic BP as accurate, in accordance with NICE guidelines. If a patient has hypertension, we don't need to use ABPM or HBPM unless there are concerns, but for patients with diabetes, both sitting and standing BP should be checked due to the risk of postural hypotension, especially if affected by autonomic neuropathy.
Our patient is being treated with an ACEI, lisinopril 20 mg OD, which aligns with NICE guidance. For people with diabetes of any age and ethnicity background, an ACEI or ARB is recommended as first-line treatment, given their protective effect on the kidneys. This is especially important for patients with early stages of CKD like our patient.
I'd like to mention that our patient takes ibuprofen regularly for osteoarthritis. However, this is concerning for two reasons: it can increase blood pressure, and it's a nephrotoxic drug that can worsen CKD. We'll discuss this more when reviewing her osteoarthritis treatment.
Our patient’s BP is 142/88. NICE says that the target BP for people under the age of 80 is below 140/90, making her reading borderline. OK, what would I do?
Our patient's BP is 142/88, with a target BP below 140/90 for people under 80, making her borderline. We are starting her on dapagliflozin for her diabetes so we could see what happens to her BP. SGLT2 inhibitors, due to their diuretic effect, can sometimes have a BP lowering effect, especially when given in combination with antihypertensive agents such as ACEIs. We are probably going to advise this patient to stop or drastically reduce the use of ibuprofen, so that may also have a positive effect on her BP. Because her current BP is not desperately high, we could afford to wait for a few weeks to see if her BP drops spontaneously.
What would I do if the BP remained above target? We know that the dose of lisinopril can be increased to 40 mg and up to a maximum to 80 mg daily. However, we also know that ACEIs and ARBs are generally less effective as monotherapy in patients of African or African-Caribbean family background because these patients have a tendency towards a low renin state and a lower cardiac output, together with increased peripheral resistance.
So, should we increase her dose of lisinopril or should we start her on a combination with, for example, a CCB? We know that CCBs are the preferred choice for patients of African and African-Caribbean family background if they do not have diabetes.
You can obviously assess her individual circumstances but, in general terms, it would be better to optimise the dose of lisinopril to the maximum tolerated dose and increase it further if possible. ACEIs and ARBs are important in the treatment of chronic kidney disease, and, avoiding these drugs in African-Caribbean patients may inadvertently contribute to worse outcomes for chronic kidney disease in these patients.
Moving on to her osteoarthritis, we don't know which joints are affected, but we do know her symptoms are well controlled on regular ibuprofen 400mg BD.
It's important to keep in mind that NICE recommends the following:
A non-pharmacological approach should be attempted first. This involves ensuring that the patient has engaged with physiotherapy and weight loss strategies. If the patient has not received support for this, they should be referred accordingly.
If non-pharmacological management has not been effective, a topical non-steroidal anti-inflammatory drug should be offered for knee osteoarthritis, and it should be considered for other osteoarthritis-affected joints as well. If this treatment has not been tried before, we should recommend it.
If topical treatment is not effective, NICE suggests using oral NSAIDs only at the lowest effective dose and for the shortest possible time. We should review whether to continue treatment regularly. For instance, if the patient is taking ibuprofen regularly, we should assess whether they could cope with intermittent use or a lower dose of, say, 200mg twice daily.
Finally, if the patient requires regular NSAIDs, it should be given with gastroprotection to minimise the risk of upper gastrointestinal bleeding. Therefore, we should be prescribing a proton pump inhibitor, such as omeprazole 20 mg daily, as long as they are taking ibuprofen.
Additionally, NICE advises against the use of paracetamol or weak opioids in osteoarthritis unless they are used infrequently for short-term pain relief and all other treatments have been ineffective or unsuitable.
Now, let’s look at her hyperlipidaemia and her QRISK2 score of 20%. We know that she has no history of cardiovascular disease so we are assessing her for primary prevention.
We should normally assess patients’ QRISK2 score before starting a statin. After starting a statin, we should focus on the decrease of non-HDL cholesterol with statin therapy instead of the actual QRISK2 score since, by starting a statin, we already know that the patient is at high risk.
Let's take a closer look at the NICE guidelines on this subject:
NICE recommends using the QRISK2 tool to assess cardiovascular risk for primary prevention in individuals up to age 84, including those with type 2 diabetes. However, it's not suitable for people already at high risk due to other medical conditions such as pre-existing CVD, type 1 diabetes, CKD with an eGFR less than 60 and / or albuminuria, familial hypercholesterolemia, or other genetic causes.
For patients like this one with a QRISK2 score of 10% or higher, NICE recommends offering atorvastatin 20 mg for primary prevention of CVD in addition to lifestyle advice.
After starting atorvastatin 20 mg, we'll recheck the patient's lipids after three months and assess non-HDL cholesterol reduction. If non-HDL cholesterol hasn't decreased by more than 40%, we'll reinforce lifestyle advice and adherence and consider increasing the atorvastatin dose to 40 mg, and later on up to 80 mg, if the patient is at higher risk due to comorbidities.
Regarding this particular patient, we assume that the score is pre-treatment, and even though she is taking 40 mg of atorvastatin, her lipids are still high. We'll need to check her pre-treatment non-HDL cholesterol to see if the 40% drop has been achieved. If not, we may consider increasing the dose to 80 mg daily.
Before we move on, let's quickly summarize what NICE recommends for patients already on statins:
We'll measure liver transaminase enzymes before starting a statin, within three months of starting or increasing the dose, and again at 12 months, unless clinically indicated.
Consider annual non-fasting blood tests for non-HDL cholesterol to inform discussions or annual reviews with the patient.
Do not offer a statin in combination with fibrate, nicotinic acid, or a bile acid sequestrant. However, combining with ezetimibe may be appropriate for patients with primary hypercholesterolemia.
Now, let's turn our attention to the patient's asthma. The history says that her asthma is well controlled with on-demand reliever therapy as needed, in this case, Salbutamol inhaler 2 puffs when required.
According to NICE guidelines, patients with infrequent, short-lived wheezing and normal lung function can be treated with SABA reliever therapy alone. However, if symptoms indicate the need for maintenance therapy, for example, asthma-related symptoms occurring three or more times a week or symptoms causing waking at night, a low dose of an ICS such as standard beclomethasone 100mcg, one or two inhalations twice daily should be offered.
Moving on to depression, NICE recommends SSRIs such as fluoxetine as the first choice for most people, due to their good safety profile and tolerability. Tricyclic antidepressants, on the other hand, have a higher risk of danger in overdose. Lofepramine is indicated as the TCA with the best safety profile. Antidepressants are usually taken for at least 6 months, and for some time after symptoms remit.
We would need to investigate whether the patient is ready to reduce or stop the medication. NICE advises that withdrawal symptoms can occur with a wide range of antidepressant medication, including tricyclics, SSRIs, and SNRIs. It's also important to note that some commonly used antidepressants, such as paroxetine and venlafaxine, are more likely to be associated with withdrawal symptoms, so particular care is needed with them. However, fluoxetine's prolonged duration of action means that it can sometimes be safely stopped by taking 20mg alternate days for a period of time. For people taking higher doses, such as 40mg to 60mg fluoxetine a day, a more gradual withdrawal schedule should be used.
If a person experiences withdrawal symptoms when they stop taking antidepressant medication or reduce their dose, NICE recommends reassuring them that they are not having a relapse of their depression. It's important to explain that these symptoms are common, and that relapse does not usually happen as soon as medication is stopped or the dose is lowered. Additionally, it's important to note that even if the medication is restarted or the dose is increased, withdrawal symptoms may take a few days to disappear.
In summary, here are the steps we will be taking:
We will start with dapagliflozin at 5mg and increase to 10mg daily if the patient tolerates it.
We will monitor the patient's blood pressure while on dapagliflozin and consider increasing the dose of lisinopril to 40mg once daily if necessary.
We will encourage the patient to attend physiotherapy and weight management support sessions, while also starting topical NSAIDs and reducing oral ibuprofen as much as possible. Any future doses of ibuprofen will come with gastroprotection, such as omeprazole, and the patient will be warned about the nephrotoxic effects of ibuprofen.
We will check the patient's non-HDL cholesterol levels and consider increasing atorvastatin to 80mg once daily if the current statin therapy has not resulted in a 40% reduction in non-HDL cholesterol.
We will evaluate the patient's asthma control and, if needed, offer low-dose inhaled corticosteroids, such as beclomethasone 100mcg, one or two inhalations twice daily, if the patient experiences asthma-related symptoms three or more times a week or wakes up at night due to asthma symptoms.
Finally, we will discuss the patient's depression and assess whether she is ready to gradually discontinue fluoxetine.
It is important to note that these steps will likely require multiple appointments to complete.
Please keep in mind that this is only my interpretation of the patient's case, and there may be alternative treatment options available.
We have come to the end of this episode. I hope that you have found it useful. Thank you for listening and good-bye
Intro / outro music: Track: Halfway Through — Broke In Summer [Audio Library Release]
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 graduallyover 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‑releasemetformin, 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.
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.
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
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
As ever, remember that there is a YouTube version of this episode and the link to the YouTube channel is also in the episode description.
People with type 2 diabetes have twice as many coronary heart disease and strokes as those without it. At first glance, you could think it was too much, but in reality, this is a significant improvement. Previous data indicated that the risk of cardiovascular disease increased by around four to six times. Thus, doubling the risk indicates a significant improvement. Blood pressure control and strict cholesterol treatment are now standard management. And as a result, there are far fewer atherosclerotic events that affect persons with type 2 diabetes. However, as a result, heart failure is now becoming more common.
According to research, people with type 1 diabetes have steadily experienced a decline in CVD, CV mortality, and CV hospitalisation. However, there is still a significant gap between those who have type 1 diabetes and those who do not.
The same research, however, revealed that those with type 2 diabetes had experienced a far bigger improvement, resulting in, at worst, a doubling of the risk of cardiovascular disease (CVD), hospitalisation for CVD, and cardiovascular mortality. And once more, this has been associated with intensive blood pressure and cholesterol management; perhaps this is something that might be applied to patients with type 1 diabetes, where the focus is still often on glycaemia-related issues.
According to other studies, people with type 2 diabetes have an increased chance of developing heart failure. This increased risk is most noticeable in the middle-aged group, perhaps those up to the age of 55, and it appears to be less of an issue as people get older. Therefore, heart failure is now one of the most significant CVD symptoms in persons with type 2 diabetes.
Atherosclerotic disease, coronary heart disease, or strokes are still the earliest signs of vascular illness in the non-diabetic population. However, peripheral vascular disease or heart failure are the most typical early presentations of vascular disease in persons with type 2 diabetes.
Heart failure in diabetics is caused by a number of different ways. First, excess atherosclerotic disease. Also, the heart's ability to operate can then be impacted by hypertension itself. Additionally, a lot of our patients are now recovering from myocardial infarctions, and as time passes, the ventricle develops scarring that exacerbates heart failure. Furthermore, apart from atherosclerosis and hypertension, there is a heart condition known as "diabetic cardiomyopathy" that damages the myocardium. The ventricle becomes extremely stiff due to a combination of metabolic and pathological causes, making it difficult for the ventricle to relax and fill. And finally, diabetic autonomic neuropathy also plays a role in the development of heart disease in patients with diabetes.
Variations in glycaemic control and chronic hyperglycaemia are recognised epidemiologically as risk factors for cardiovascular disease in people with diabetes.
There are now numerous things we can do for our patients with diabetes to lower cardiovascular risk, just as there are numerous risk factors for heart disease in those with diabetes. One factor we take into account is lifestyle, but studies have shown that this is a pretty unsatisfactory intervention when we focus on heart disease, frequently failing to show any benefit on lowering cardiovascular disease rates. However, we continue to believe that lifestyle intervention is crucial for some people.
After bariatric surgery, cardiovascular morbidity and death have been demonstrated to decrease in people with type 2 diabetes.
Controlling glycaemia, blood pressure, and cholesterol are crucial for patients with diabetes.
Numerous trials have examined glycaemic control in persons with type 1 and type 2 diabetes. The effects of intensive glycaemic control on microvascular and macrovascular complications were investigated in these trials.
In the DCCT study which looked at type 1 diabetes patients, strict glycaemic management resulted in a highly significant decrease in retinopathy and nephropathy. Although the initial decline in cardiovascular events was modest, subsequent studies revealed that, up to 30 years after the initial intense management, the persons who received intensive management saw a decline in cardiovascular disease, as well as total mortality. As a result, a relatively short time of intense control has long-lasting repercussions on the cardiovascular system. This phenomenon is known as the "legacy effect" or "metabolic memory."
The UKPDS trial showed that strict glycaemic control in the first 10 years from diagnosis resulted in significant decreases in retinopathy, nephropathy, and neuropathy in individuals with newly diagnosed type 2 diabetes. There was, however, a rise in serious hypoglycaemia as well. Following UKPDS for a further 10 years, that is, for a total of 20 years of follow-up, there was a highly significant reduction in myocardial infarctions and mortality even if the initial reduction in myocardial infarction was not statistically significant. Again, the initial 10-year period of strict management following diagnosis has been shown to have long-lasting effects in lowering cardiovascular disease.
In contrast, other studies that examined the intensive management of glycaemia in individuals with type 2 diabetes who had this condition for a while revealed either no benefit in terms of cardiovascular disease or an increase in mortality in the intensive treatment group as a result of individuals receiving large amounts of insulin, massive weight gain, and very frequent hypoglycaemia.
A meta-analysis of all type 2 diabetes research findings revealed a decline in coronary heart disease but no impact on overall mortality. In light of this, we can say that glycaemic control does not have a very potent effect when compared, for instance, to blood pressure or cholesterol.
In conclusion, it is best if rigorous glycaemic intervention occurs as soon as possible following diagnosis if we are to receive cardiovascular benefits from it. And once someone has had diabetes for ten years or longer, it is doubtful that treating their glycemia will result in any significant cardiovascular benefits. At least this is supported by the evidence from older anti-diabetic medications. Research results may vary with newer medications because more advanced diabetic treatments now show improved cardiovascular risk in addition to lowering blood pressure and producing weight loss.
We will now look at individual treatments and their effect on cardiovascular disease.
The data for metformin comes from the UKPDS, where a very small subset experienced further benefits in terms of lower rates of myocardial infarction, cardiovascular disease, and overall mortality.
Secondary outcome data for pioglitazone showed significant decreases in cardiovascular death, myocardial infarction, and stroke. However, there were also adverse effects such weight gain, fluid retention, and a rise in fractures. As a result, pioglitazone is not that frequently used.
DPP4Inhibitors have been the subject of numerous studies. Major adverse cardiovascular events, or MACE, which were the focus of all these investigations, were unaffected. These medications have a modest glycaemic impact and are not extremely powerful. Therefore, it is not that surprising that MACE have not been affected.
A surprise side effect of saxagliptin and a subgroup of individuals using alogliptin was a large rise in heart failure hospitalizations. In conclusion, we can state that DPP-4 inhibitors do not affect MACE and that some of them have increased hospitalisation for heart failure, even if this has not always been confirmed in the other trials.
SGLT-2 inhibitors have been investigated in numerous cardiovascular outcome trials.
Empagliflozin, canagliflozin, and dapagliflozin have all demonstrated a highly significant decrease in heart failure hospitalisation and a significant decrease in severe adverse cardiovascular events (MACE).
A meta-analysis of SGLT2 inhibitor studies was able to show that the SGLT-2 inhibitors significantly decreased subsequent MACE events for patients with atherosclerotic disease. A very substantial decrease in heart failure hospitalisation followed for patients with heart failure or had a high cardiovascular risk.
Although it has been noted that SGLT-2 inhibitors have a fairly early onset of benefit, the mechanism of benefit is yet unknown.
A number of cardiovascular outcome trials using GLP 1 agonists have demonstrated significant decreases in major adverse cardiovascular events, cardiovascular mortality, and overall mortality. However, there was no impact on heart failure hospitalisation.
The GLP-1 receptor agonists' mechanism of action is equally unknown. However, it has been noted that the improvement appears to be gradual rather than abrupt, as was the case with SGLT-2 inhibitors. And it has been widely assumed that the advantages relate to a slowing down of atherosclerosis progression. Theoretically, combining SGLT-2 inhibitors with GLP-1 receptor agonists may result in additional cardiovascular benefits and this is also a new area of research.
Several recommendations and consensus statements have recently taken into account the findings of the cardiovascular outcome trials using SGLT-2 inhibitors and GLP-1 receptor agonists. The joint ADA/EASD consensus statement is a good illustration of this. It advises that, after metformin, you thoroughly assess the patient's cardiovascular status and that, if the patient has heart failure, you should consider SGLT-2 inhibitors as the next therapy. Consider using either SGLT-2 inhibitors or a GLP-1 receptor agonist if the patient has atherosclerotic disease or is at high risk of it.
One of the most researched strategies to try and lower cardiovascular risk in patients with diabetes is lipid lowering, notably using statins. We can now confirm, thanks to a meta-analysis, that coronary disease, stroke, and coronary revascularization can all be reduced by up to 25% for every 1 mmol decrease in LDL cholesterol. The meta-analysis included participants with existing cardiovascular disease (or "secondary prevention") as well as those without known cardiovascular disease (or "primary prevention"). And both groups experienced a similar reduction of about 25%.
A second meta-analysis revealed that those with diabetes who took high-dose statins benefited even more.
Renal outcomes were the subject of a third meta-analysis. It was confirmed in this meta-analysis that patients with diabetes and chronic kidney disease, or CKD, also benefited from decreases in atherosclerotic events. Therefore, it appears that statins are a treatment that can lower cardiovascular events in diabetes at all stages, including CKD as well as primary and secondary prevention.
Other methods of lowering cholesterol have been less promising.
Only minimal improvements for patients with diabetes were seen in trials with ezetemibe and fibrates.
Trials using PCSK9-inhibitors, a different innovative family of lipid-lowering medications, have been more encouraging, showing a significant decrease in adverse cardiovascular events.
All of the individuals who participated in these lipid-lowering investigations were older than 40. Therefore, the data suggests that statins are beneficial for diabetic patients over the age of 40, regardless of the baseline risk. Therefore, recommendations state that, in diabetes, statins should be started as soon as you reach the age of 40, regardless of your baseline risk or cholesterol level. The extent to which this benefit is reduced for those who are younger remains unknown, and different guidelines take different approaches to this. In general, the guidelines try to identify younger subjects who have other cardiovascular risk markers, such as microalbuminuria, or perhaps other microvascular complications, such as retinopathy. According to some recommendations, statins should be started in the younger age group for those who have these comorbidities.
Patients with diabetes have been included in many blood pressure-lowering trials over the years because high pressure is a clear risk factor for the development of cardiovascular disease. The advantages of decreasing blood pressure in persons with diabetes have been highlighted by combining all of these research studies into one very thorough meta-analysis.
Lowering of blood pressure led to a decrease in total mortality, cardiovascular disease, coronary heart disease, and strokes. Lowering blood pressure also slowed the onset of heart failure. The meta-analysis also took a look at microvascular events and found that reducing blood pressure has definite advantages in the development of renal failure, retinopathy, and albuminuria. Therefore, there is no question that decreasing blood pressure is advantageous in diabetes in both large and small vessel disease.
Other meta-analyses have demonstrated that lowering blood pressure is more important than the antihypertensive medication used. Since ACE inhibitors and angiotensin receptor blockers appear to have a minor advantage over other blood pressure-lowering medications, most guidelines recommend using them as a first line of treatment in diabetes.
Although studies in the non-diabetic population have recommended lower BP targets, such as a systolic BP of 120 mmHg, different guidelines now come out with somewhat different targets due to a variation in the outcomes of the diabetic and non-diabetic research. The majority of guidelines advise starting blood pressure medication for those with diabetes if their readings are over 140/90, but after that, the objectives can range from 140/80 to 130/80 mmHg, with the lower target being set for those with higher cardiovascular risk.
Aspirin medication has been the subject of many meta-analyses looking at primary prevention in diabetes. There hasn't been any evidence of a clear benefit, and risks have been identified, including a rise in gastrointestinal bleeding and the risk of developing haemorrhagic stroke.
Again, trials and their subgroups have been interpreted slightly differently. And some guidelines now advise against using aspirin for primary prevention in anyone who has diabetes. However, other guidelines would suggest trying to identify group of subjects at a greater risk, maybe due to comorbidities like CKD, and use aspirin in those people. However, it should be highlighted that in those people, the risk of bleeding also tends to be higher.
Research studies on multiple risk factor interventions have also been conducted, examining the combined effects of lipid-lowering therapy, blood pressure-lowering therapy, and better glycaemic management.
Unsurprisingly, after four years of intervention, there was a 50% reduction in the risk for diabetic nephropathy, retinopathy, and neuropathy development. After eight years, there was a 50% relative risk decrease for coronary bypass procedures, myocardial infarction, strokes, amputations, and CVD death.
After a 13-year follow-up, there was a 50% relative risk decrease in the rate of mortality. And finally, a 21-year follow-up revealed that this early, multiple risk factor intervention in our patients increased their life expectancy by over eight years. As a result, we can conclude that using all of these treatments together has an even bigger impact.
The fact that all SGLT2 inhibitors regularly reduced the number of heart failure hospitalizations led researchers to wonder if they would also be able to treat heart failure in persons without diabetes. As a result, more studies investigating SGLT2 inhibitors in heart failure populations without diabetes were carried out.
The outcomes are remarkably reliable. There were significant decreases in total mortality as well as a decline in cardiovascular death and heart failure hospitalizations. So, it was shown that, whether you had diabetes or not, the benefit was proportionately the same.
Dapagliflozin currently has a licence in Europe for the treatment of heart failure in both diabetic and non-diabetic patients. As a result, we'll start to notice regular use of these medications in non-diabetic patients.
It's critical that the patient's primary care physician is aware of the rationale behind prescribing the SGLT2 inhibitor, including whether it is given for diabetes control, for the improvement of heart failure prognosis or, of course, the third indication, which is now giving it to patients with chronic kidney disease (CKD) to enhance their renal prognosis.
If we're going to begin treating people with heart failure with dapagliflozin, or any other SGLT2 inhibitor, it's crucial that we first fully characterise the patient. We must determine whether a patient has diabetes or not and, if so, what medications are being used to manage it. If a patient has low HbA1c levels, taking, for example, a sulphonylurea or insulin, and is then given an SGLT-2 inhibitor for heart failure prognosis, there is a risk that this will result in hypoglycaemia. In these patients, it would be necessary to lower the insulin dosage or perhaps even discontinue some forms of treatment. On the other end of the spectrum, introducing an SGLT-2 inhibitor to a patient with a very high HbA1c without lowering the HbA1c first, would potentially increase the risk of ketoacidosis. Therefore, communication between cardiologists and diabetologists will be crucial in this regard.
We have come to the end of this episode. I hope that you have enjoyed it and found it useful and I hope that you will join me in the next one. Thank you for listening and goodbye.
