Real life complex patient: NICE on diabetes, hypertension, hypertriglyceridemia and hypothyroidism

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:

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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/

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

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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: 

• HbA1c is 68 mmols/mol/8.4% (therefore poorly controlled) 
• Cholesterol 5.9 
• Triglycerides 5.72 
• HDL 0.97 

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

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

• Thyroid function tests show a borderline low T4 of 9 (NR 9-19.1) and a raised TSH of 9.88 (NR 0.35-4.94 
• ACR normal 
• FBC and other routine blood tests were normal.  
• His BMI is 32, so he is obese 
• His BP is 147/89 
• His PMH includes: 
• Hypothyroidism 
• T2DM 
• His regular treatment is with: 
• Levothyroxine 200mcg daily 
• Metformin 500 mg TDS 

He comes to discuss his test results, feeling well in himself. His obesity is long-standing and being managed with diet and lifestyle advice. He has had hypothyroidism for 15 years and, on prompting, he says that he is feeling a little tired 

So, let’s have a look at the guidelines. As usual I will focus on the NICE guidelines and we will have to looks at the guidelines on type 2 diabetes, hypertension, prevention of cardiovascular disease, and hypothyroidism  

Let’s look at his diabetes first. 

Firstly, NICE says that we need to consider if rescue therapy is necessary for symptomatic hyperglycaemia with insulin or a sulfonylurea. However, he is well and asymptomatic so we do not have to do this. 

We see that his current dose of metformin 500 mg 3 times a day is not enough to control his diabetes. So, given that his renal function is completely normal.  we should increase the dose to the maximum of 2000mg daily, that is, 1000mg twice a day. However, this is unlikely to be enough to bring his HbA1c of 68 or 8.4% to target. And let’s remember that according to NICE we should strive for the following targets: 

·      Lifestyle management only— 48 mmol/mol (6.5%). 

·      A single drug not associated with hypoglycaemia (such as metformin) — 48 mmol/mol (6.5%). 

·      Drug treatment associated with hypoglycaemia (such as a sulfonylurea): 53 mmol/mol (7.0%). 

·      Always adjust for people who are frail, elderly or with other co-morbidities 

This patient is young and otherwise well so we should aim to treat him aggressively. 

NICE says that for people not controlled on metformin alone, we should consider dual therapy but which?  

We need to assess the person's cardiovascular status and risk to determine whether they have chronic heart failure, established atherosclerotic cardiovascular disease, or are at high risk of developing cardiovascular disease. 

This patient does not have heart failure or cardiovascular disease but using an online calculator, his 10-year QRISK3 score is 12%. So, being over 10%, we will consider him at high risk of developing CVD.  

And NICE says that if the patient is at high risk of developing cardiovascular disease, we will consider an SGLT-2 inhibitor with proven cardiovascular benefit in addition to metformin. 

This is good because it seems quite clear that his obesity is a problem and both metformin and SGLT2 inhibitors promote weight loss. 

Because we would want to manage him aggressively, I would advise him to increase metformin straightaway and as soon as we know that it is tolerated, which could be a matter of days, we could start the SGLT2 inhibitor. 

SGLT2 inhibitors with proven cardiovascular benefit includes dapagliflozin, empagliflozin and canagliflozin 

Remember that SGLT2 inhibitors are associated with an increased risk of DKA and lower limb amputation. Therefore, before starting an SGLT2 inhibitor, we need to check whether the person may be at increased risk of diabetic ketoacidosis (DKA), for example if: 

• they have had a previous episode of DKA 
• they are unwell with intercurrent illness 
• Or they are following a very low carbohydrate or ketogenic diet, and if so, not to start the SGLT2 inhibitor until they have changed their diet. We will also advise them not to start this type of diet while they are on this medication.  
•  
• The increased risk of lower-limb amputation has been shown with Canagliflozin but there is some concern that the risk may be a class effect. We will need to ensure that foot care is optimised before starting the SGLT2 inhibitor.  
•  
• So, this would be my pharmacological action from a diabetic perspective. Increase metformin to 1000mg BD and start an SLGT2 inhibitor, for example, dapagliflozin 10 mg OD. 
•  
• Now let’s have a look at his BP, which is elevated at 147/89. 
•  
• NICE says that people under the age of 80 should have a BP below 140/90. 
•  
• To confirm the diagnosis, we should arrange ambulatory or home blood pressure monitoring and if the average is greater than 135/85 we will start him on antihypertensive treatment. We have more or less established that he does not have end-organ damage because of his normal renal function, normal urinary albumin / creatinine ratio and, looking at his records, normal fundoscopy, as he attends for his annual diabetic retinal screening programme. To be strict, we should also arrange an ECG to ensure that there are no signs of left ventricular hypertrophy.  
•  
• Let’s assume that his BP is indeed above the target. What treatment should we start? 
•  
• NICE says that for someone with diabetes of any ethnicity and any age, we should start and ACEI or ARB. We know that ACEI confer significant renal protection in diabetes, so we will start him on an ACEI, something like lisinopril 2.5 mg daily, monitoring his renal function and increasing the dose gradually according to our clinical judgement. This patient is of Asian family background but remember that if the patient is of Afro-Caribbean family origin, we should opt for an ARB in preference to an ACEI. This is because Afro-Caribbean patients are considered “low renin responders” and therefore ACEI are less effective in this group. 
•  
• Now let’s look at his lipids and what we would do based on the NICE guideline on prevention of cardiovascular disease. 

Firstly, we will calculate his CV risk.Using the online QRISK3 calculator we find that his 10-year risk is 12% Further details are: 

Your 10-year QRISK®3 score  12% 

The score of a healthy person with the same age, sex, and ethnicity 2.6% 

Relative risk**  4.6 

Your QRISK®3 Healthy Heart Age 66 

But remember that NICE also says that the CVD risk may be underestimated by risk assessment tools if the triglyceride levels are raised, which is this patient’s case. 

Could this be treated with lifestyle alone? Because we need to treat him aggressively, I would say no. Furthermore, his cholesterol has been elevated well over 5 mmol/l (200 mg/dL) for the last 3 years so it is clear that diet and exercise alone are not doing the job.  

NICE says that for Primary prevention: 

• If lifestyle modification is ineffective or inappropriate, we will offer a statin, generally atorvastatin 20 mg, for the primary prevention of CVD to people who have a 10% or greater 10‑year CVD risk using the QRISK assessment tool.  
• For people 85 years or older we will still consider atorvastatin 20 mg as statins may be of benefit in reducing the risk of non‑fatal MI. 

Should we do anything different from the point of view of his triglycerides?  

Well, first of all, we will look to see if they have been this high for long. Previous entries show levels moderately elevated but not to this degree. 

Triglycerides are also affected by diabetes control and it may very well be that once his hyperglycaemia improves, and his HbA1c goes down, his triglycerides will too. 

Triglycerides may be also elevated in situations where excess alcohol is consumed. So, we should enquire about this.

And hypothyroidism can also influence lipids in general and triglycerides in particular. Improving his hypothyroidism treatment is also likely to improve the lipid situation.  

Also, atorvastatin will have some effect on the triglycerides, although this effect may not be very pronounced.     

Other drugs like fibrates, such as fenofibrate, are potent agents in reducing triglyceride levels. However, NICE do not recommend their use. In fact, NICE says that: 

• For the prevention of CVD, we should not offer Fibrates, Nicotinic acid, Bile acid sequestrants or Omega‑3 fatty acid compounds, either alone or in combination therapy. 

In summary, I would start him on atorvastatin 20 mg daily and recheck his liver tests and lipids 3 months later, perhaps on a fasting sample, to see if the triglycerides have improved too. Remember that we aim for a greater than 40% reduction in non‑HDL cholesterol and, if this target is not achieved, we will consider increasing the dose. 

And finally, what about his hypothyroidism? He has had it for some time and is on a dose of 200 mcg daily of levothyroxine but his T4 is still on the low side and his TSH is elevated. And he also complains of being tired at times. 

In terms of management of hypothyroidism, NICE says that we should adjust the dose according to symptoms and TFT results, aiming to maintain TSH and T4 levels to within or close to the normal reference range. We should also review the person and recheck TSH levels every 3 months after every dose change. 

The BNF says that for adults under 50 the dose adjustments would be in steps of 25–50 micrograms every 3–4 weeks, according to response. However, a little fly in the ointment is that the BNF recommends the maintenance dose to be up to 200 micrograms once daily. And this is precisely this patient’s dose.  

Sometimes patients do need higher doses but, perhaps we should discuss compliance with him given that it may very well be that he is not taking it regularly and this is why his tests results are not in the normal range.  

Right, so this would be my initial management of this real-life patient: more metformin, dapagliflozin, lisinopril, Atorvastatin and discuss if increasing Levothyroxine is necessary. Remember that this is only my interpretation of the guidelines. 

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