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 31st 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 Diabetes in Primary Care podcast which can be found here:

·      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

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 

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Transcript

Thank you for downloading and welcome. This podcast is intended for healthcare professionals bringing you medical information about the management of diabetes from a Primary Care perspective. My name is Fernando Florido and I am a GP in the United Kingdom.

 

In this episode I am going to tell you about the updated NICE guidelines in the management of type 2 diabetes in adults or guideline NG28. These guidelines were last updated on 31st March 2022. In this episode I am only going to refer to the drug management of blood glucose rather than the full guideline. The other recommendations have not really changed significantly and, if you are interested in them, you can listen to the previous podcasts that I have uploaded on the subject. You will be able to find links to them in the podcast description. I have also uploaded YouTube videos on this subject and other NICE guidance. A link to access the channel can be found in the podcast description.

 

 

As ever, all information is correct at the time of recording and all views and opinions are my own. I hope that you enjoy this episode.

You may be aware that until the publication of this NICE guideline update, there has been quite a disparity between the advice given by NICE and other international guidelines such as those of the American Diabetes Association or the European Association for the Study of Diabetes, amongst many others. This is because of the funding of the British National Health System which expects NICE to assess not only the clinical merits of each medical intervention, including drugs, but also their cost effectiveness. After this update, the NICE guidelines are now more similar to the American and European guidelines when considering SGLT2 inhibitors but they still differ very significantly when it comes to GLP mimetics. This is because NICE, at this stage, does not consider them to be cost effective except in some very specific circumstances.

You must know that there is a visual summary to provide an overview of the recommendations and additional information to support medicines choice and a link will be placed in the podcast description.

Now, when it comes to Choosing drug treatments

and before we start any medication, we will need to discuss with adults with type 2 diabetes the benefits and risks of drug treatment and the options available and base the choice of drug treatments on:

·      the person's individual clinical circumstances, preferences and needs

·      the effectiveness of the drug treatments in terms of metabolic response and cardiovascular and renal protection

·      safety and tolerability of the drug treatment

·      monitoring requirements

·      the licensed indications or combinations available

·      cost (if 2 drugs in the same class are appropriate, choose the option with the lowest acquisition cost). 

We just need to be aware that there are separate guidelines for the drug treatment during pregnancy and the pre-pregnancy period.

IN terms of Rescue therapy at any phase of treatment

If an adult with type 2 diabetes is symptomatically hyperglycaemic, we need to consider insulin or a sulfonylurea, and review treatment when blood glucose control has been achieved. 

Now, when it comes to First-line drug treatment

There is a visual summary on first-line drug treatment that offers an overview of the recommendations. I will also put a link to this in the podcast description.

We will basically start by offering standard-release metformin as first-line drug treatment to adults with type 2 diabetes. 

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

Because SGLT2 inhibitors can improve cardiovascular outcomes, we will do the following:

·      If they have chronic heart failure or established atherosclerotic cardiovascular disease, we will offer an SGLT2 inhibitor with proven cardiovascular benefit in addition to metformin.

·      If they are at high risk of developing cardiovascular disease, we will consider an SGLT2 inhibitor with proven cardiovascular benefit in addition to metformin. 

  

To assess whether people are at high risk of developing cardiovascular disease, it is recommended to use the QRISK2 tool for adults with type 2 diabetes. We need to be aware that lifetime cardiovascular risk may be underestimated in people aged under 40 using this tool, so we need to consider other risk factors too.

There are 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- I will put a link to these guideline in the podcast description.

In terms of Choosing an SGLT2 inhibitor with cardiovascular benefit

The evidence shows that SGLT2 inhibitors as a class of drugs are most likely to be cost effective in combination with metformin and there are also varying levels of certainty in the clinical trials and the meta-analyses about:

·      which individual SGLT2 inhibitors were effective at improving cardiovascular outcomes

·      whether there were real differences in cardiovascular benefits between the different SGLT2 inhibitors.

For example, for hospitalisation for heart failure, empagliflozin, canagliflozin, ertugliflozin and dapagliflozin produced a clinically meaningful reduction. However, the network meta-analysis could not differentiate between the SGLT2 inhibitors.

When starting an adult with type 2 diabetes on dual therapy with metformin and an SGLT2 inhibitor as first-line therapy, we will introduce the drugs sequentially, starting with metformin and checking tolerability. We will then start the SGLT2 inhibitor as soon as metformin tolerability is confirmed. 

We will gradually increase the dose of standard-release metformin over several weeks to minimise the risk of gastrointestinal side effects in adults with type 2 diabetes. 

If an adult with type 2 diabetes experiences gastrointestinal side effects with standard‑release metformin, we should consider a trial of modified‑release metformin. 

However, if metformin is contraindicated or not tolerated, for first-line drug treatment we will consider the following:

·      If they have chronic heart failure or established atherosclerotic cardiovascular disease, we will offer an SGLT2 inhibitor with proven cardiovascular benefit.

·      And If they are at high risk of developing cardiovascular disease, then we will consider it. 

For first-line drug treatment in adults with type 2 diabetes who are not in either of these groups, if metformin is contraindicated or not tolerated and we will consider:

·      a DPP‑4 inhibitor or

·      pioglitazone or

·      a sulfonylurea although

·      an SGLT2 inhibitor can be prescribed for people for whom

• a sulfonylurea or pioglitazone is not appropriate and
• a DPP‑4 inhibitor would otherwise be prescribed

There have been multiple instances of avoidable diabetic ketoacidosis (DKA) associated to SGLT2 inhibitors and addressing modifiable risk factors before starting an SGLT2 inhibitor could reduce the risk of DKA and make the drug safer for the person with type 2 diabetes.

Therefore, before starting an SGLT2 inhibitor, we must check whether the person may be at increased risk of diabetic ketoacidosis (DKA), for example if:

·      they have had a previous episode

·      they are unwell with intercurrent illness

·      they are following a very low carbohydrate or ketogenic diet. 

And we will address modifiable risks for DKA before starting an SGLT2 inhibitor. For example, for people who are following a very low carbohydrate or ketogenic diet, they may need to delay treatment until they have changed their diet. 

Adults with type 2 diabetes who are overweight or obese may wish to try a ketogenic diet to reverse or reduce the severity of their diabetes or induce remission. However, because there may be an increased risk of DKA associated with SGLT2 inhibitors and such diets, it is important to tell people about these risks and to advise them to discuss any planned change to a very low carbohydrate or ketogenic diet with their healthcare professional first.

 

Therefore we will advise adults with type 2 diabetes who are taking an SGLT2 inhibitor about the need to minimise their risk of DKA by not starting a very low carbohydrate or ketogenic diet without discussing it with their healthcare professional, because they may need to suspend SGLT2 inhibitor treatment. 

 

When it comes to patients with type 2 diabetes and chronic kidney disease, there are recommendations on SGLT2 inhibitors in a separate section in this guideline. These are as follows:

For adults with type 2 diabetes and CKD who are taking an ARB or an ACE inhibitor (titrated to the highest tolerated dose) we will:

·      offer an SGLT2 inhibitor (in addition to the ARB or ACE inhibitor) if the ACR is over 30 mg/mmol and

·      consider an SGLT2 inhibitor (in addition to the ARB or ACE inhibitor) if the ACR is between 3 and 30 mg/mmol

·      however, because some of the SGLT2 inhibitors cannot be prescribed when the eGFR levels are too low, we will need to ensure that the eGFR thresholds are met.

We must note that not all SGLT2 inhibitors have been licensed for the indication of CKD, although this is likely to change over time. Dapaglifozin is definitely one of the licensed ones. This is because clinical trial evidence suggests that dapagliflozin plus standard care is more effective than standard care alone in slowing disease progression.

There is separate NICE guidance for it which I will also put in the podcast description.

(This dapaglifozin in CKD guidance broadly says the same as what has just been stated although the ACR threshold is 22.6 or more:

·      Dapagliflozin is recommended as an option for treating chronic kidney disease (CKD) in people with diabetes:

•  only as an add-on to optimised standard care including the highest tolerated licensed dose of angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), unless these are contraindicated, and

§ eGFR is between 25 and 75 at the start of treatment and

§ ACR is 22.6 mg/mmol or more.)

When reviewing or considering changing treatments for adults with type 2 diabetes, we should think about and discuss the following:

·      We need to take into account factors such as adverse effects, adherence to existing medicines, advice about diet and lifestyle and prescribed doses and formulations

·      We also need to consider stopping medicines that have had no impact on glycaemic control or weight, unless there is an additional clinical benefit, such as cardiovascular or renal protection

·      We will also consider whether switching rather than adding drugs could be effective

·      Plus we will take into account all the considerations about treatment choice described earlier – such as individual clinical circumstances, individual preferences and needs, the effectiveness, safety and tolerability of the drug etc

When considering adding an SGLT2 inhibitor at any stage after first-line treatment, there are some considerations to consider and these are that

·      If they have or develop chronic heart failure or established atherosclerotic cardiovascular disease, we need to offer an SGLT2 inhibitor or replace an existing drug with the SGLT2 inhibitor.

·      If they are or become at high risk of developing cardiovascular disease, we will have to consider doing this, that is, either adding an SGLT2 inhibitor or replacing an existing drug with the SGLT2 inhibitor.

When it comes to Treatment options if further interventions are needed

There is a visual summary on treatment options if further interventions are needed and I will put a link to this in the podcast description.

First of all, we need to introduce drugs used in combination therapy in a stepwise manner, checking for tolerability and effectiveness of each drug. 

As we have already mentioned, if monotherapy has not controlled HbA1c we will consider adding a second drug, that is an SGLT2 inhibitor for people who meet the cardiovascular criteria or, otherwise, a DPP‑4 inhibitor or pioglitazone or a sulfonylurea 

If dual therapy with metformin and another oral drug has not continued to control HbA1c we will consider either:

·      triple therapy, by Switching or adding treatments from different drug classes up to triple therapy including combinations of Metformin, sulphonylureas, DPP‑4 inhibitors and, for people who meet the cardiovascular criteria, SGLT2 inhibitors.

·      Or we could consider going directly from dual therapy to starting insulin

However, if metformin is contraindicated or not tolerated and dual therapy with 2 oral drugs has not controlled HbA1c, then we will need to consider going directly to insulin treatment

Finally, if triple therapy with metformin and 2 other oral drugs is not effective, not tolerated or contraindicated, we will consider triple therapy by switching one drug for a GLP‑1 mimetic only if certain strict conditions are met. These are:

·      If the body mass index (BMI) of 35 kg/m2 or higher (adjusting accordingly for people from Black, Asian and other minority ethnic groups) and there are specific psychological or other medical problems associated with obesity or

·      If they have a BMI lower than 35 kg/m2 and:

o  for whom insulin therapy would have significant occupational implications or

o  weight loss would benefit other significant obesity-related comorbidities. 

We will only continue GLP‑1 mimetic therapy if there is a reduction of at least 11 mmol/mol [1.0%] in HbA1c and weight loss of at least 3% of initial body weight in 6 months). 

 

When considering Insulin-based treatments

Patients should receive a structured programme using active insulin dose titration that encompasses full training and support as well as appropriate driving advice.

When starting insulin, we should continue to offer metformin for people without contraindications or intolerance but we will review the continued need for other blood glucose lowering therapies. 

In general, combination therapy with a GLP‑1 mimetic and insulin should only be considered along with specialist care advice and ongoing support from a consultant-led multidisciplinary team. 

Insulin in combination with other oral hypoglycaemic agents, including SGLT2 inhibitors can be an option for treating type 2 diabetes

When it comes to managing their therapy,

We will start insulin from a choice of the following insulin types and regimens:

·      First, we will offer NPH insulin injected once or twice daily according to need.

·      But we will consider starting both NPH and short‑acting insulin (particularly if the person's HbA1c is 75 mmol/mol [9.0%] or higher), administered either:

o  separately or

o  as a pre-mixed (biphasic) human insulin preparation.

·      We will also consider, as an alternative to NPH insulin, using insulin detemir or insulin glargine if:

o  the person needs help from someone else to inject insulin, and use of insulin detemir or insulin glargine would reduce the frequency of injections from twice to once daily or

o  the person is restricted by recurrent symptomatic hypoglycaemic episodes or

o  the person would otherwise need twice‑daily NPH insulin injections in combination with oral glucose‑lowering drugs.

·      We will consider pre-mixed (biphasic) preparations that include short‑acting insulin analogues, rather than pre‑mixed (biphasic) preparations that include short‑acting human insulin preparations, if:

o  the person prefers injecting insulin immediately before a meal or

o  hypoglycaemia is a problem or

o  blood glucose levels rise markedly after meals. 

We will consider switching to insulin detemir or insulin glargine from NPH insulin if there are issues with NPH such as not reaching their target HbA1c because of significant hypoglycaemia or who experience significant hypoglycaemia or who cannot use the device needed to inject NPH or who need help from someone else to administer insulin injections and for whom switching to one of the long‑acting insulin analogues would reduce the number of daily injections. 

We will monitor adults with type 2 diabetes who are on a basal insulin regimen (NPH insulin, insulin detemir or insulin glargine) for the need for short‑acting insulin before meals (or a pre‑mixed [biphasic] insulin preparation). 

We will monitor adults with type 2 diabetes who are on pre‑mixed (biphasic) insulin for the need for a further injection of short‑acting insulin before meals or for a change to a basal-bolus regimen

When starting an insulin for which a biosimilar is available, we will use the product with the lowest acquisition cost. 

Insulin delivery

I will not say much about the guidance on insulin delivery for adults with type 2 diabetes, but you can see the section on insulin delivery in the NICE guideline on type 1 diabetes, and I will put a link in the podcast description to access it.

 

This is the end of this episode. I hope that you have enjoyed it and I hope that you will join me in the next one. Thank you for listening