Download KINES 2015 NICE T2DM guidance Jan 16

Keele’s ‘Important News and Evidence’ Service
KINES
Rapid Update
January 2016
Updated NICE guidance on Type-2 Diabetes – recommendations on drug treatments
The long-awaited update of NICE Guideline on Type-2 Diabetes (NG28) was published in December 2015. This
guideline had been subject to a second round of consultation following concerns raised about the first draft published
in January 2015. Some important changes have now been made in the final guideline to address these concerns.
Key to these changes, and to implementing the new guidance, is the emphasis on working with patients to
personalise care.
Treatment should be tailored to their needs and circumstances, taking into account personal preferences,
comorbidities, risks from polypharmacy, and ability to benefit from long-term interventions where there is reduced
life expectancy.
Such an approach is especially important in the context of multi-morbidity.
This has particular relevance in helping patients decide on management of blood glucose control, a topic covered
in a new Patient Decision Aid developed by NICE.
Below we consider the guideline’s recommendations on drug treatments, including blood pressure management and
lipid modification, as well as blood glucose lowering therapies. Regarding future iterations of this guideline, NICE has
indicated there are plans in place to establish a Standing Update Committee on diabetes. This may enable more rapid
updating of this guidance, to better keep pace with developments in this rapidly evolving clinical area.
Key documents/resources:
Type 2 diabetes in adults (NG28). December 2015. www.nice.org.uk/guidance/ng28
Algorithm for blood glucose lowering therapy in adults with type 2 diabetes. NICE. December 2015
http://www.nice.org.uk/guidance/ng28/resources/algorithm-for-blood-glucose-lowering-therapy-in-adults-with-type-2-diabetes2185604173.
Patient
decision
aid:
first
intensification
of
blood
glucose
therapy.
NICE.
December
2015.
http://www.nice.org.uk/guidance/ng28/resources/patient-decision-aid-2187281197
What are the key drug recommendations for managing cardiovascular (CV) risk in adults
with type 2 diabetes?
Blood pressure management:
Recommendations in the new guideline (NG28) largely follow those in previous guidance published in 2009.
It sets thresholds for medication use if lifestyle advice does not reduce blood pressure to below 140/80 mmHg (or
below 130/80 mmHg if there is kidney, eye or cerebrovascular damage).
As previously, the mainstay of first-line antihypertensive drug treatment is an angiotensin converting enzyme
(ACE) inhibitor, with addition of a calcium channel blocker, or a thiazide or thiazide-related diuretic. (See NG28 for
full recommendations).
This differs somewhat with the NICE 2011 hypertension guideline (CG127) for people without type 2 diabetes,
which favours thiazide-like diuretics (e.g. indapamide), in preference to conventional thiazide diuretics, such as
bendroflumethiazide or hydrochlorothiazide.
Antiplatelet therapy for primary prevention:
NG28 advises not to offer antiplatelet therapy (aspirin or clopidogrel) for adults with type 2 diabetes without
cardiovascular disease (CVD). This change in guidance follows evidence that has emerged in recent years that
the risks of adverse events, such as bleeding, exceed the benefits in this population.
Lipid modification with statins:
Lipid modification is an important intervention in type 2 diabetes. As recommended in section 1.5 (antiplatelet
therapy) of NG28, people with type 2 diabetes should be managed according to the 2014 Clinical Guideline on
Lipid Modification (CG181):
o QRISK2 should be used to estimate risk in those who do not have established CVD and people offered
atorvastatin 20 mg daily with >10% 10-year risk of CVD.
o For type 2 diabetes, it advises considering increasing the dose up to 80 mg atorvastatin daily, if a 40%
reduction in non HDL-cholesterol is not achieved.
o For secondary prevention, all should be given atorvastatin 80 mg daily.
o Fibrates are no longer recommended.
What are the key drug recommendations on managing blood glucose in adults
with type 2 diabetes?
Summary of targets for HbA1c in NG28:
For adults with type 2 diabetes managed either by lifestyle and diet, or by lifestyle and diet combined with a single
drug not associated with hypoglycaemia, support the person to aim for an HbA 1c level of 48 mmol/mol (6.5%).
For adults on a drug associated with hypoglycaemia (for example, a sulfonylurea), support the person to aim for
an HbA1c level of 53 mmol/mol (7.0%).
In adults with type 2 diabetes, if HbA1c levels are not adequately controlled by a single drug and rise to
58 mmol/mol (7.5%) or higher:
o reinforce advice about diet, lifestyle and adherence to drug treatment, and
o support the person to aim for an HbA1c level of 53 mmol/mol (7.0%), and
o intensify drug treatment.
Consider relaxing the target HbA1c level on a case-by-case basis, with particular consideration for people with
type 2 diabetes who are older or frail:
o who are unlikely to achieve longer-term risk-reduction benefits, for example, people with a reduced life
expectancy
o for whom tight blood glucose control poses a high risk of the consequences of hypoglycaemia, for
example, people who are at risk of falling, people who have impaired awareness of hypoglycaemia, and
people who drive or operate machinery as part of their job
o for whom intensive management would not be appropriate, for example, people with significant
comorbidities.
The above ‘personalisation’ or ‘relaxation’ of HbA1c levels appear to address concerns raised during consultation that
these targets do not have a strong evidence base, and that uncritical adherence may cause harm, particularly with
regard to the risks of hypoglycaemia. These risks have been seen in some randomised controlled trials (RCTs), such
as ACCORD, and observed in some large database studies, e.g. Currie at al., 2010. It is important that these
‘relaxations’ are carefully explored when considering intensification of treatment.
Drug treatments to reduce blood glucose:
Blood glucose lowering therapy recommendations are summarised in the guideline’s algorithm, reproduced at the
end of this document. Some important considerations follow:
The use of sodium glucose co-transporter 2 (SGLT2) inhibitors is not described in the guideline or the
algorithm.
o Instead NG28 advises that NICE guidance on canagliflozin in combination therapy for treating type 2
diabetes (TA315), dapagliflozin in combination therapy for treating type 2 diabetes (TA288) and
empagliflozin in combination therapy for treating type 2 diabetes (TA366), should be referred to.
o In some respects these omissions could cause confusion. Because of the rapidly emerging evidence for
these drugs (for example, the EMPA-REG OUTCOME study), this may be the type of issue that lends
itself to rapid revision by a NICE Standing Update Committee for diabetes.
Metformin remains a key role as the first-line drug treatment. (Note - the need to monitor renal function and
modify treatment, if necessary.)
If metformin is contraindicated or not tolerated, consider initial drug treatment with: a dipeptidyl peptidase-4
(DPP-4) inhibitor, or pioglitazone, or a sulfonylurea (SU). A preference for one of these is not stated. This now
means that an SU is no longer the main second-line therapy.
If metformin has not continued to control HbA1c to below the individually agreed threshold for intensification,
consider dual therapy with: metformin and a DPP-4 inhibitor or, metformin and pioglitazone (taking into
account risks of adverse events specific to pioglitazone, such as heart failure), or metformin and an SU.
Although repaglinide had a prominent place in the draft guidelines, this has not carried over into the final
guideline.
Three recently published, large RCTs have looked at whether DDP-4 inhibitors have an effect on CV outcomes in
type 2 diabetes (SAVOR-TIMI 53, TECOS and EXAMINE). In these studies, DPP-4 inhibitors did not reduce CV
events. (Further information on the TECOS study is available in the July 2015 KINES Rapid Update, available via
our website http://centreformedicinesoptimisation.co.uk/.)
NG28 gives guidance on triple oral therapy (see the algorithm) in those who can take metformin.
NG28 also looks at when to consider introducing injectable glucagon-like peptide 1 (GLP-1) mimetic drugs
(exenatide, liraglutide, lixisenatide and dulaglutide). These are associated with weight loss.
o
It advises to consider using these in severely obese people (generally BMI 35 kg/m 2 or higher) with
associated physical or psychological problems if triple therapy is not effective, not tolerated or
contraindicated (see algorithm).
o They should be used in combination therapy with metformin and an SU.
o They can also be considered for people with less severe obesity where weight loss is particularly
beneficial or where insulin might cause occupational problems (driving or operating machinery).
It advises to stop the GLP-1 mimetic if the person has not had a beneficial metabolic response (a reduction of at
least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body weight in 6 months).
These ‘starting and stopping rules’ remain important as audit criteria.
The advice for triple oral therapy and the GLP-1 mimetic drugs only applies in the guideline if the person is
taking metformin; in those who cannot take metformin or who are intolerant, the next step after dual therapy (e.g.
an SU and DDP-4, or pioglitazone and an SU, or pioglitazone and DDP-4) would be to consider insulin therapy.
Another important recommendation is only to offer a GLP-1 mimetic in combination with insulin with
specialist care advice and ongoing support from a consultant-led multidisciplinary team. There has been
enthusiasm to combine a GLP-1 mimetic with insulin, as this use may offset the weight gain seen with insulin.
Guidance on use of insulin is similar to that in the previous guideline, with the mainstay of basal insulin treatment
being NPH insulin for most people (see algorithm). When this is started, metformin should be continued in those
people able to take it.
The guideline advises not to routinely offer self-monitoring of blood glucose (SMBG) levels, unless the
person is on insulin or has had episodes of hypoglycaemia, or the person is on oral medication that may increase
their risk of hypoglycaemia while driving or operating machinery. SMBG should also be offered if the person is
pregnant, or is planning to become pregnant (see NICE 2015 guideline [NG3] on diabetes in pregnancy).
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