Diabetes in Primary Care

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:

·      Colour version:https://1drv.ms/b/s!AiVFJ_Uoigq0l3MBwm5sUpEybW8r?e=xio6pz

·      Printer friendly version:https://1drv.ms/b/s!AiVFJ_Uoigq0l3RhABLRM2_pQQOz?e=jzuMxb

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

·      The NICE GP YouTube Channel:NICE GP - YouTube

Prescribing information links:

·      Website:https://cks.nice.org.uk/topics/diabetes-type-2/prescribing-information/dpp-4-inhibitors/

·      Download PDF:https://1drv.ms/b/s!AiVFJ_Uoigq0liBvuQq8_0Cd-GSz?e=NnL56J

·      Website:https://cks.nice.org.uk/topics/diabetes-type-2/prescribing-information/glp-1-receptor-agonists/

·      Download PDF:https://1drv.ms/b/s!AiVFJ_Uoigq0liFRycIZPaVfj-lC?e=a2QTNY

Intro / outro music:Track: Halfway Through — Broke In Summer [Audio Library Release]

Music provided by Audio Library Plus

Watch:https://youtu.be/aBGk6aJM3IU

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Transcript

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: 

·      The path lab has not calculated LDL because triglycerides >4.5 

·      Liver and Renal function tests are normal with an eGFR of 97  

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: 

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: 

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: 

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 

"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: 

ChatGPT prompt to create a patient:  

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.

·      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: 

The full NICE Guideline on hypertension (NG136) can be found here:  

The full NICE Guideline on Type 2 diabetes (NG28) can be found here:  

·      Overview | Type 2 diabetes in adults: management | Guidance | NICE 

The full NICE guidance on osteoarthritis (NG226) can be found here: 

·      Overview | Osteoarthritis in over 16s: diagnosis and management | Guidance | NICE 

The full NICE guidance on cardiovascular disease risk reduction (CG181) can be found here: 

·      Overview | Cardiovascular disease: risk assessment and reduction, including lipid modification | Guidance | NICE

The full NICE guidance on asthma (NG80) can be found here: 

·      Overview | Asthma: diagnosis, monitoring and chronic asthma management | Guidance | NICE 

The full NICE guidance on depression in adults (NG222) can be found here: 

·      Overview | Depression in adults: treatment and management | Guidance | NICE 

Intro / outro music: Track: Halfway Through — Broke In Summer [Audio Library Release]   

Transcript  

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 

Her regular Medications are:

Fortunately, she tolerates all medications well without any side effects.

We also have her blood test results, which show the following:

·      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  

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 | NICEor

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

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

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

Intro / outro music: Track: Halfway Through — Broke In Summer [Audio Library Release]

Music provided by Audio Library Plus

Watch:https://youtu.be/aBGk6aJM3IU

Free Download / Stream:https://alplus.io/halfway-through

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 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.

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:

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

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

This episode also appears in the Primary Care guidelines podcast: 

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

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

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

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

·      The NICE GP YouTube Channel: NICE GP - YouTube 

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Transcript

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Right, time to decide. What would I do?

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

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

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

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

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

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

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

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

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

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

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

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

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:

https://www.youtube.com/channel/UClrwFDI15W5uH3uRGuzoovw 

The online course can be found on the EASD learning website:

https://easd-elearning.org/courses/cardiovascular-health-and-diabetes/

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Transcript

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.

 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.

Episode: EASD ADA consensus guidelines on the overall approach in glucose lowering medication in type 2 diabetes

This podcast is intended for healthcare professionals. My name is Fernando Florido and I am a GP in the United Kingdom. In this episode I go through the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) consensus guidelines on the overall approach in glucose lowering medication in type 2 diabetes. I will firstly give you a list of the changes to the previous consensus recommendations followed by a description of the consensus recommendations flowchart on the subject. The original article was published on 19 December 2019 with a subsequent correction published on 15 May 2020.

There is a YouTube version of this episode in the NICE GP YouTube Channel that you can access here:

·      https://www.youtube.com/channel/UClrwFDI15W5uH3uRGuzoovw

This episode also appears in the

Primary Care guidelines podcast:

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

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

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

Diabetes in Primary Care podcast:

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

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

·      Apple podcasts: https://podcasts.apple.com/us/podcast/diabetes-in-primary-care/id1562910252

The ADA-EASD consensus guidelines can be found here:

·      Website:

o  https://link.springer.com/article/10.1007/s00125-019-05039-w

·      Or download here:

o  https://1drv.ms/b/s!AiVFJ_Uoigq0lW-4rilnP_mruV41?e=FjPLGo

The Summary of the changes to the previous consensus recommendations can be

·      Viewed on website above:

o  https://link.springer.com/article/10.1007/s00125-019-05039-w

·      Or downloaded here:

o  https://1drv.ms/b/s!AiVFJ_Uoigq0lW72FZuzZZiv8bPr?e=7Fib8M

The Visual summary “glucose lowering medication in type 2 diabetes- overall approach” can be found here:

·      Website:

o  Figure 1 | 2019 update to: Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) | SpringerLink

·      Or download here:

o  https://1drv.ms/u/s!AiVFJ_Uoigq0lXCNFscGYei60BiV?e=3n0Ern

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This podcast is intended for healthcare professionals. Thank you for listening and welcome to a new episode, bringing you medical information and clinical guidance from a primary care perspective. My name is Fernando Florido and I am a GP in the United Kingdom.

In today’s episode I am going to go through the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) consensus guidelines on the overall approach in glucose lowering medication in type 2 diabetes.

I will firstly give you a list of the changes to the previous recommendations followed by a description of the consensus recommendations flow chart.

If you have been following previous episodes, you may be familiar with the updated NICE guidelines on the management of type 2 diabetes. However, the NICE recommendations, primarily followed in the UK, have some substantial differences when compared to other international recommendations and this is why I have decided to do this episode today. You will notice that the main difference with NICE refers to the use of GLP1 mimetics which NICE considers to be less cost effective. However, from a clinical perspective, there is now ample evidence in their favour, which justifies a wider use as described in the consensus guidelines.

I will put in the description below a link to download the full article as well as the summary of the changes and the flow chart. There is a YouTube version of this episode and other NICE guidance on the NICE GP YouTube Channel and a link to access it can be found in the podcast description. Because of the visual nature of the flow chart, I would highly recommend watching the YouTube video if you can.

Although describing visual aids as audio files can be challenging, I hope that you find the content clear and informative.

Right, let’s go right in. So, we are going to start looking at the European Association for the Study of Diabetes and the American Diabetes Association consensus guidelines on managing hyperglycemia in type 2 diabetes, published in December 2019, corrected in May 2020 and I have put links in to it in the episode description.

Now, before starting the treatment flow chart, we are going to go through the changes to the consensus recommendations and this is just a brief summary of what the changes are.

As a general consideration we will say that, in high-risk patients, the decision to treat with a GLP 1 receptor agonist or an SGLT 2 inhibitor should be considered independently of the HbA1c. This is because these agents have been proven to reduce major adverse cardiovascular events, hospitalisation for heart failure, cardiovascular deaths and CKD progression.

We will say that in patients with established atherosclerotic cardiovascular disease, the level of evidence for cardiovascular benefit is greatest for GLP 1 receptor agonist and this is in terms of reducing major adverse cardiovascular events.

And because of this, to reduce the risk of cardiovascular disease, the GLP 1 receptor agonists can also be considered in patients who have no cardiovascular disease but who are at high risk of cardiovascular disease.

For patients with heart failure, especially if their heart failure has a reduced ejection fraction, that is, an ejection fraction less than 45%, or if they have CKD with an eGFR between 30 and 60 and microalbuminuria, with urine albumin creatinine ratio greater than 30 particularly if it is greater than 300, the level of evidence is greatest for SGLT 2 inhibitors. So, SGLT 2 inhibitors are recommended with patients with heart failure and equally the SGLT 2 inhibitors are recommended for patients we CKD to prevent progression of CKD as well as the cardiovascular outcomes.

Obviously, because there is a link between SGLT 2 inhibitors and an increased risk of amputation, patients with foot ulcers or at high risk of amputation, should only be treated with SGLT 2 inhibitors after careful shared decision making around the risks and benefits and with comprehensive education and foot care and amputation prevention.

Well, that was the summary of the changes. Now we are going to dive in straight into the flow chart, which is titled: “glucose lowering medication in type 2 diabetes: overall approach”. And in the right top corner there is a note that tells us that, to avoid clinical inertia, we need to review the patients regularly, ideally every three or six months.

Now, the first thing that the flow chart tells us is that the first line therapy is always metformin and comprehensive lifestyle including weight management and physical activity. So, metformin first of all, and then, we are going to see if there are indicators of high risk or established atherosclerotic cardiovascular disease, CKD or heart failure. If the patient has any of these, then we will consider independently of the HbA1c the treatment.

This side of the flow chart then divides in two, one if cardiovascular disease predominates or, two, if heart failure or CKD predominate.

So, if atherosclerotic cardiovascular disease predominates, either because there is established cardiovascular disease or there are indicators of high risk for getting cardiovascular disease, then we will preferably give a GLP 1 receptor agonist with proven cardiovascular disease benefit and the chart tells us at the bottom in the notes that proven cardiovascular benefit means that it has a label indication for reducing cardiovascular events.

If you cannot give or do not want to give a GLP 1 receptor agonist then we will give an SGLT 2 inhibitor with proving cardiovascular benefit, as long as the eGFR is adequate. And again, it reminds us at the bottom of the chart that we have to be aware that SGLT 2 inhibitor labelling varies by region and individual agents with regard to the indicated level of eGFR for initiation and continued use.

Right, so we repeat again, independently of the HbA1c and if cardiovascular disease predominates, we will give either GLP 1 receptor agonist or an SGLT 2 inhibitor.

And then, we will look at the HbA1c and if the HbA1c remains above the target then we will consider further intensification of the treatment.

For patients who are on GLP 1 receptor agonists we will give an SGLT 2 inhibitor and, likewise, if they had initiated an SGLT 2 inhibitor then we will give them a GLP 1 receptor agonist. As an alternative, we can give a DPP 4 inhibitor if the patient is not on a GLP 1 receptor agonist, and this is because of their mode of action or we can also give basal insulin, pioglitazone or a sulphonylurea. So, we are just going to mix and match those agents, always preferably starting with GLP 1 receptor agonist, then SGLT 2 inhibitors and then we can give a DPP 4 inhibitor if the patient is not on a GLP 1 receptor agonist, or basal insulin, pioglitazone or a sulphonylurea.

And, also in the notes at the bottom, it tells us that degludec and U 100 glargine have demonstrated cardiovascular disease safety. It also tells us that a low dose of pioglitazone may be better tolerated though less well studied for cardiovascular effects and, in terms of sulphonylureas, it reminds us that we should choose later generations of sulphonylureas to lower the risk of hypoglycaemia and glimepiride has shown similar cardiovascular safety to the DPP 4 inhibitors.

So, that concludes the section where cardiovascular disease predominates. Now if heart failure or CKD predominate, particularly if it is reduced ejection fraction heart failure or if CKD has an eGFR between 30 and 60 and microalbuminuria at least 30mg per gram or more, we will use preferably an SGLT 2 inhibitor with evidence of reducing heart failure and / or CKD progression in cardiovascular outcome trials, as long as the EGFR is adequate.

So, it tells us in the notes at the bottom that both empaglifozin and canaglifozin have shown reduction in heart failure and also reduced CKD progression in cardiovascular outcome trials. Canaglifozin has primary renal outcome data from CREDENCE and dapaglifozin has primary heart failure outcome from the DAPA HF trial. But all these details may be becoming less and less relevant because it is now increasingly thought that the SGLT 2 inhibitors have a class effect.

Now if an SGLT 2 inhibitor is not tolerated or contraindicated or if the eGFR is less than adequate, we will give a GLP 1 receptor agonist with proven cardiovascular benefit.

So, it is more or the other way round from the cardiovascular disease branch. There we gave a GLP 1 receptor agonist first and then an SGLT 2 inhibitor. Here, in heart failure of CKD we are going to give an SGLT 2 inhibitor first and then GLP 1 receptor agonist second.

And, again, we need to remember that if a patient has heart failure or CKD, we will consider this treatment with an SGLT2 inhibitor or a GLP 1 receptor agonist independently of the HbA1c.

And then, we will look at the HbA1c, and if the HbA1c is above the target, we will consider further treatment.

The first thing that we have to consider is that we need to avoid pioglitazone in the setting of heart failure because it tends to worsen it because of fluid retention. We will try to stick to agents with cardiovascular safety. So, for patients on an SGLT 2 inhibitor, we will consider a GLP 1 receptor agonist. Or we can give a DPP 4 inhibitor but not saxagliptin in the setting of heart failure, as long as the patient is not on a GLP 1 receptor agonist. Alternatively, we can give basal insulin or a sulphonylurea.

So, in summary, after an SGLT 2 inhibitor and a GLP 1 receptor agonist, if we need to give anymore drugs, we will avoid pioglitazone and saxagliptin in in the setting of heart failure. We can consider a DPP 4 inhibitor, if not on a GLP 1 receptor agonist, or basal insulin or a sulphonylurea.

Right, this ends the branch of heart failure or CKD patients.  So, we have now covered both if a patient has got atherosclerotic cardiovascular disease, heart failure or CKD. However, if a patient has not got those conditions and they are not at high risk of those conditions, then we will give metformin and then will be guided by the HbA1c in order to decide whether to give more treatment.

And we will divide this treatment in three, depending on whether, one, we want to minimise hypoglycaemia, two, we want to minimise weight gain or promote weight loss and, three, when cost of treatment is a major issue. So again, we divide the treatment on whether we focus on hypoglycaemia, on weight or on cost.

Firstly, we will look at the branch where minimising hypoglycaemia is our priority. And for those patients, we will use any of the agents that are not associated with hypoglycaemia. That is, a DPP 4 inhibitor, a GLP 1 receptor agonist, an SGLT 2 inhibitor or pioglitazone. So, we give dual therapy with metformin and one of those drugs. If the HbA1c remains above target then we will give triple therapy with metformin and any combination of the drugs already mentioned, a DPP 4 inhibitor, a GLP 1 receptor agonist, an SGLT 2 inhibitor or pioglitazone bearing in mind that we must not combine a GLP 1 receptor agonist and a DPP 4 inhibitor. But all other combinations are allowed.

And then, if the HbA1c remains above target on triple therapy, we will continue with additions of other agents so we can go to quadruple therapy.

Finally, if the HbA1c remains above target. Then we will consider the addition of a sulphonylurea or basal insulin. And with sulphonylureas we will choose the later generations with lower risk of hypoglycaemia such as glimepiride or we will consider a basal insulin with lower risk of hypoglycaemia. And there is a small note at the bottom of the chart that tells us that the insulin with lowest risk of hypoglycaemia is degludec and glargine U300, followed by glargine U100 and detemir, followed by finally NPH insulin.

Now, the second branch is when we are going to focus on the weight because we need to minimise weight gain or promote weight loss. In these cases, we will give either at GLP 1 receptor agonist or an SGLT 2 inhibitor because both these agents are associated with weight loss. And a small note at the bottom of the chart tells us the GLP 1 receptor agonists with good efficacy for weight loss. The best one is semaglutide, followed by liraglutide, then dulaglutide, then exenatide and finally lixisenatide. So, if we can, we will give them always either semaglutide or liraglutide.

And then if the HbA1c remains above target then we will give the second of those two agents, so, if the patient is had a GLP 1 receptor agonist, we will give an SGLT 2 inhibitor and if they have had an SGLT 2 inhibitor then we will give in GLP 1 receptor agonist.

And if the HbA1c remains above target, then we will start quadruple therapy because the patient would already be on metformin, a GLP 1 receptor agonist and an SGLT 2 inhibitor. But if this combination is not tolerated or contraindicated, then the lowest risk of weight gain is with a DPP 4 inhibitor and this is because the DPP 4 inhibitors have got weight neutrality, but that can only be given if the patient is not already on a GLP 1 receptor agonist.

If the DPP 4 inhibitor is not tolerated or contraindicated or if the patient is already on a GLP 1 receptor agonist, we should use cautiously a sulphonylurea, pioglitazone or basal insulin, and this is because all these agents are associated with weight gain.

Finally, the last branch of the flowchart is when we are going to focus on the cost, because cost is a major issue. And there is a note at the bottom of the page that is going to tell us when we should consider cost to be a major issue. Therefore, cost should be our focus if there are no specific comorbidities, that is, no established cardiovascular disease, there is a low risk of hypoglycaemia and weight is not a real concern.

Also, there is a warning in terms of cost, saying that we need to consider country and region-specific cost of drugs because, in some countries for example, pioglitazone can be relatively more expensive and a DPP 4 inhibitor relatively cheaper.

So, looking at the flowchart, if cost is a concern, after metformin we will start with either a sulphonylurea or pioglitazone, which are generally the cheapest agents and if the HbA1c is above target, we will go into triple therapy with metformin, a sulphonylurea and pioglitazone. And if the HbA1c remains above target, then we will consider either insulin therapy, giving basal insulin with the lowest acquisition cost or we can consider a DPP 4 inhibitors or an SGLT 2 inhibitors with the lowest acquisition cost. Or, in other words, we go into quadruple therapy according to whatever is the most cost-effective combination.

Right, this is it, we have completed the review of the EASD ADA consensus guidelines flow chart. So, this is the end of this video and the summary of the consensus recommendations. There is also a YouTube version of this episode in the NICE GP YouTube Channel and I will leave a link in the episode description. Thank you for listening and I hope that you will join me in the next one.

My name is Fernando Florido and I am a GP in the United Kingdom. In this video I go through the Visual summary “choosing medicines for first-line and further treatment” corresponding to the 2022 updated NICE Guideline: Type 2 diabetes in adults: management (NG28 guideline), updated on 29^th June 2022. The video focuses on the drug treatment recommendations in blood glucose management in adults with Type 2 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:

https://www.youtube.com/channel/UClrwFDI15W5uH3uRGuzoovw

This podcast also appears in the Primary Care Guidelines podcast which can be found here:

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

·      Spotify: https://feeds.redcircle.com/2587ad78-7730-48f6-894e-f1f4178e37c3

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

NICE Guideline NG28 can be found here:

https://www.nice.org.uk/guidance/ng28

The full NG28 full guideline PDF document can be found here:

·      Website:

https://www.nice.org.uk/guidance/ng28/resources/type-2-diabetes-in-adults-management-pdf-1837338615493

·      If outside the UK, you can download it here: https://1drv.ms/b/s!AiVFJ_Uoigq0lWqK_tYk1rnOolRO

The visual summary “choosing medicines for first-line and further treatment” can be found here:

·      Website:

https://www.nice.org.uk/guidance/ng28/resources/visual-summary-full-version-choosing-medicines-for-firstline-and-further-treatment-pdf-10956472093

·      If outside the UK, you can download it here: https://1drv.ms/b/s!AiVFJ_Uoigq0lWugUmhgaYv1PHyf

Intro / outro music: Track: Halfway Through — Broke In Summer [Audio Library Release]

Music provided by Audio Library Plus

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Transcript

Thank you for listening and welcome to a new episode of this podcast bringing medical information and NICE guidance from a primary care perspective. My name is Fernando Florido and I am a GP in the United Kingdom.

Now, imagine that we have Mr. Johnson, who is 78 and has type 2 diabetes. His diabetes control is reasonable or metformin, 500mg BD. With an HbA1c of 7.1% or 54 mmol/mol, but he has just developed stable angina. How should his diabetic treatment change? We have covered the 2022 NICE diabetes management update in previous episodes, but perhaps we need a quick reminder?

And this is what we’re going to do today because in this video I am going to go through the flow charts produced by NICE in respect of the blood glucose management in type 2 diabetes. The full guideline has 59 pages in a PDF format and NICE has produced a 5-page summary on the blood glucose management. This video is going to focus on the two flow charts that will advise how to choose first line medicines and how to choose medicines for further treatment.

I will put in the description below a link to download the full NICE guideline as well as the five-page summary. There is a YouTube version of this episode and other NICE guidance on the NICE GP YouTube Channel and a link to access it can be found in the podcast description. Because of the visual nature of the flow chart, I would highly recommend watching the YouTube video if you can.

Although describing visual aids as audio files can be challenging, I hope that you find the content clear and informative.

Now the first flow chart that we are going to look at is the one about how to choose first line medicines. It is only one page and there is a combination of arrows that will guide us through the treatment pathways and a number of boxes with further information and clarification on the treatments described.

Right at the top of the chart, we find a box that tells us about rescue therapy and it reminds us that for patients with symptomatic hyperglycaemia, we will consider insulin or a sulphonylurea and then review the treatment when their blood glucose control has been achieved.

Then the next step is to assess the HbA1c, the cardiovascular risk and kidney function. Obviously, as you know, to calculate the cardio vascular risk with, for example, the QRISK2 tool, we will need to know the patient’s age, sex, smoking status, blood pressure and the total cholesterol/HDL ratio.

Now, having checked the renal function, before starting to follow the pathway, there is a little box on the left telling us that for information on using SGLT 2 inhibitors for people with type 2 diabetes and CKD, there is specific guidance that is not on this flow chart and we will have to refer to CKD section of the diabetic guideline.

So, after we have done our initial assessment with the HbA1c, cardiovascular risk and kidney function, the flow chart divides into three categories. One, it could be that the patient is not at high cardiovascular risk. Two, that the patient has chronic heart failure or established atherosclerotic cardio vascular disease. Or three, that the patient has a high risk of cardiovascular disease, which is defined as a QRISK 2 of 10% or higher over ten years, or an elevated lifetime risk.

Now, the first pathway would be when the patient is not at high risk of cardio vascular disease and for these patients, we will offer metformin, or, if there are gastrointestinal side effects, we will give Metformin slow release. Now if metformin is contraindicated, we will consider one of the other antidiabetic agents, either a DPP-4 inhibitor, pioglitazone or a sulphonylurea, although it does also tell us that SGLT 2 inhibitors can also be given as monotherapy for some patients. Basically, NICE recommends an SGLT 2 inhibitor as monotherapy in people who can’t take metformin and for whom the diabetic control is poor, and only if a DPP-4 inhibitor would otherwise be prescribed and a sulphonylurea or pioglitazone is not appropriate. So, it is fairly restrictive.

We also see a small note saying that using your ertugliflozin to reduce cardiovascular risk when the blood glucose is well controlled was an off-label use.

So, if no cardiovascular risk, we give metformin first and if contraindicated one of the other agents, sulphonylurea, pioglitazone, DPPG4 inhibitors of an SGLT2 inhibitor, although the latter with a few restrictions.

Now the second pathway would be when the patient has got chronic heart failure or established atherosclerotic cardiovascular disease. And the flow chart tells us in a box what they actually mean by established atherosclerotic cardiovascular disease, and this is fairly intuitive. It includes CHD, acute coronary syndrome, previous MI, stable angina, prior coronary or other revascularisation, cerebrovascular disease, which includes both ischemic stroke and TIAs and finally, peripheral arterial disease. So, for those patients, we will do very similar. We will start with metformin or if there are gastrointestinal side effects, we will give Metformin slow release and then, as soon as metformin tolerability is confirmed, we will offer an SGLT 2 inhibitor with proven cardiovascular benefit. And this is because SGLT 2 inhibitors have now been found to reduce cardio vascular events. However, if metformin is contraindicated, then we will give an SGLT 2 inhibitor alone. So, this is fairly straight forward.

Finally, the third option after the initial assessment is that the patient has not got cardiovascular disease but is at high risk of it. In this case, the flow chart is basically fairly similar. We will give metformin or, if there are side effects, metformin slow release and then as soon as metformin tolerability is confirmed we will consider an SGLT 2 inhibitor with proven cardiovascular benefit. And also, if metformin is contraindicated, we will consider an SGLT 2 inhibitor alone.

So, you may ask what is the difference between those two, having cardiovascular disease and being at high risk of CVD? And the difference is basically that, if the patient has got cardiovascular disease or heart failure, we will definitely offer an SGLT 2 inhibitor, whereas if a patient is only at high risk of cardiovascular disease, we will consider it. But in practice you will probably find that pathways are exactly the same, because you’re going to consider it seriously and you're going to give it unless a contraindication or other major consideration.

In the middle of the flow chart there’s a little box that reminds us that we always have to start metformin alone to assess tolerability before adding an SGLT 2 inhibitor. So, metformin is always the start.

So, this is really the flowchart on how to choose first line medicines. After this, if the person’s HbA1c is not controlled below the target or a person develops cardio vascular disease or a high risk of cardiovascular disease, then we will move to the second flow chart, which is the one about treatment options if further interventions are needed.

So, there we go. The second flow chart which is on how to choose medicines for further treatment.

Here, at the beginning, there’s another box telling us again about rescue therapy and using insulin, or a sulphonylurea for symptomatic hyperglycaemia until the levels are controlled.

Now, if further treatment options are needed, it will be because either at any point the HbA1c is not well controlled, or at any point, the cardio vascular risk or cardiovascular status change.

Right, we’re going to start with the cardiovascular risk of cardiovascular status change and we’ve got two options. The first one is that the person has or develops chronic heart failure or established atherosclerotic cardiovascular disease, and the second one is that the person develops a high risk of cardiovascular disease.

If the person has or develops chronic heart failure or established atherosclerotic cardiovascular disease, we will basically switch or add treatments to make sure that we offer an SGLT 2 inhibitor if this is not already prescribed. So, if the person develops the condition, we will either add an SGLT 2 inhibitor if the HbA1c could do with lowering further or, if the HBA 1C, is fairly low and we don’t want to lower it any more then we will switch one of the existing drugs for an SGLT 2 inhibitor.

On the other hand, if the person has or develops a high risk of cardio vascular disease, then we will consider an SGLT 2 inhibitor when switching or adding treatments. So, like before in the previous flow chart, giving an SGLT2 is slightly more imperative when the person has developed cardiovascular disease, whereas, if the person is just at a high risk, we will only consider it. But again, in practice it may not make much difference.

Now, if at any point the HbA1c is not well controlled, there is a box that tells us that we will switch or add treatments from different drug classes up to triple therapy or dual therapy if metformin is contraindicated. So basically, we will consider any combination to dual or triple therapy of the antidiabetic agents, that is, either a DPP 4 inhibitor, pioglitazone or a sulphonylurea, although it also tells us that SGLT 2 inhibitors may also be an option both in dual therapy or triple therapy.

Now you may ask when should we start insulin? Well at the bottom left corner we find a box that tells us that, when dual therapy is not enough to control the HbA1c, we can consider insulin-based therapy, with or without other drugs and there is additional guidance on how to use insulin with SGLT 2 inhibitors. So basically, if a patient goes up to dual therapy and is not well controlled, you may consider triple therapy if the patient is on metformin or just consider insulin as the next step.

And finally, what is happening to GLP 1 mimetics? Well, this is where NICE has been quite restrictive in their approach because it tells us that if triple therapy with metformin and two other oral drugs is not enough, we will consider triple therapy by switching one drug for a GLP 1 mimetic, but only for people:

·      who have a BMI of 35 or higher and specific psychological or other medical problems associated with obesity, although it does say that you can adjust the BMI to lower for people from Black, Asian and other minority ethnic groups, because these groups are at higher risk of cardiovascular disease and GLP mimetics have also been shown to reduce cardiovascular events, or

·      we can give it to patients who have a BMI lower than 35 and for whom:

o   insulin therapy would have a significant occupational implication or

o  weight loss would benefit other significant obesity related comorbidities.

Right, so this is it, we have finished our second flow chart and therefore we have come to the end of this episode, I hope that you have found it useful. There is also a YouTube version in the NICE GP YouTube Channel and I will leave a link in the podcast description. Thank you for listening and I hope that you will join me in the next one. Goodbye.

My name is Fernando Florido and I am a GP in the United Kingdom. In this podcast I go through the updated NICE Guideline: Type 2 diabetes in adults: management (NG28 guideline), updated on 31^st March 2022. The podcast focuses in the new drug treatment recommendations in blood glucose management in adults with Type 2 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:

https://www.youtube.com/channel/UClrwFDI15W5uH3uRGuzoovw 

This podcast also appears in the Primary Care Guidelines podcast which can be found here:

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

·      Spotify: https://feeds.redcircle.com/2587ad78-7730-48f6-894e-f1f4178e37c3

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

NICE Guideline NG28 can be found here:

https://www.nice.org.uk/guidance/ng28

Other links referred to in this episode:  

·      visual summary to provide an overview of the recommendations and additional information to support medicines choice

·      visual summary on first-line drug treatment

·      recommendations on using risk scores and QRISK2 to assess cardiovascular disease risk in adults with type 2 diabetes in NICE's guideline on cardiovascular disease: risk assessment and reduction, including lipid modification

·      NICE's technology appraisal guidance on dapagliflozin for treating chronic kidney disease

·      visual summary on treatment options if further interventions are needed

·      section on insulin delivery in the NICE guideline on type 1 diabetes 

Intro / outro music: Track: Halfway Through — Broke In Summer [Audio Library Release]

Music provided by Audio Library Plus

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Type 2 diabetes: prevention in people at high risk

Public health guideline [PH38]

Published: 12 July 2012 

Last updated: 15 September 2017

Found athttps://www.nice.org.uk/guidance/ph38

This podcast is intended for Health Care Professionals.

My name is Fernando Florido and I am a GP in the United Kingdom. In this podcast I go through the NICE Guideline PH38: Type 2 diabetes: Prevention in people at high risk. The podcast focuses on the clinical aspects and the administrative or commissioning guidance has been removed from the podcast.

This episode is the first of a trial using a computer voice rather than my own. If the trial is successful, it will enable me to produce content more efficiently and I hope that you will find it useful.

This podcast will be saved on a website.

Intro / outro music by Karveas, provided by YouTube Audio Library.

Stream on Spotify: https://open.spotify.com/track/7GGulw​...

Stream on Apple Music: https://music.apple.com/ru/album/when​...

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:

https://www.nice.org.uk/guidance/ng28

MHRA safety advice on the risk of cardiac side effects with domperidone

MHRA safety advice on the risk of neurological adverse effects with metoclopramide

evidence summary on oral erythromycin for gastroparesis in adults

NICE guideline on neuropathic pain in adults

NICE guideline on diabetic foot problems

NICE guideline on chronic kidney disease in adults

CKD classification according to estimated GFR (eGFR) and albumin:creatinine ratio (ACR) (table 1)

1 Recommendations | Chronic kidney disease in adults: assessment and management | Guidance | NICE

Intro / outro music by Karveas, provided by YouTube Audio Library.

Stream on Spotify: https://open.spotify.com/track/7GGulw​...

Stream on Apple Music: https://music.apple.com/ru/album/when​...

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:

https://www.nice.org.uk/guidance/ng28

Driver and Vehicle Licensing Agency (DVLA)'s Assessing fitness to drive: a guide for medical professionals

MHRA guidance on the risk of bladder cancer with pioglitazone

NICE's guidance on canagliflozin, dapagliflozin and empagliflozin as monotherapies for treating type 2 diabetes

NICE guidance on canagliflozin in combination therapy for treating type 2 diabetes

dapagliflozin in combination therapy for treating type 2 diabetes

dapagliflozin in triple therapy for treating type 2 diabetes 

empagliflozin in combination therapy for treating type 2 diabetes

the relevant section in the NICE guideline on type 1 diabetes

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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:

https://www.nice.org.uk/guidance/ng28

Hypertension in adults NICE guideline can be found here: Overview | Hypertension in adults: diagnosis and management | Guidance | NICE

Cardiovascular disease- risk assessment and reduction NICE guideline can be found here: Overview | Cardiovascular disease: risk assessment and reduction, including lipid modification | Guidance | NICE

Intro / outro music by Karveas, provided by YouTube Audio Library.

Stream on Spotify: https://open.spotify.com/track/7GGulw​...

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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.

NICE Guideline NG28 can be found here:

https://www.nice.org.uk/guidance/ng28

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.

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