Glucose monitoring and glucose lowering agents for children and young people with type 2 diabetes: summary of updated NICE guidance
BMJ 2023; 382 doi: https://doi.org/10.1136/bmj.p1686 (Published 12 September 2023) Cite this as: BMJ 2023;382:p1686
- Linyun Fou, technical analyst1,
- Juliana Chizo Agwu, consultant paediatrician2,
- Nivedita Aswani, consultant paediatrician3,
- Chirag Bakhai, general practitioner4,
- Evelien Gevers, consultant paediatric endocrinologist5 6
- 1National Institute for Health and Care Excellence (NICE), Manchester, UK
- 2Paediatrics, Sandwell & West Birmingham NHS Trust
- 3Sheffield Children’s Hospital NHS Foundation Trust, Sheffield
- 4Larkside Practice, Luton
- 5Barts Health NHS Trust, Royal London Children’s Hospital, London
- 6Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London
- Correspondence to L Fou Linyun.fou{at}nice.org.uk
What you need to know
Refer children and young people with suspected or diagnosed type 2 diabetes (T2DM) to a specialist paediatric diabetes team to ensure appropriate diagnosis, investigation, and treatment, including a continuing programme of education on how diet, physical activity, and reducing body weight can improve glycaemic control
Capillary blood glucose monitoring is now recommended for all children and young people with T2DM, and continuous glucose monitoring for people treated with insulin
Specialists should consider offering liraglutide or dulaglutide, or alternatively empagliflozin, in combination with metformin to lower blood glucose
Type 2 diabetes mellitus (T2DM) in children and young people (aged under 18 years) is a more aggressive disease than in older adults and is associated with higher risk of severe long term and potentially life threatening complications (eg, cardiovascular disease, renal disease) compared with other types of diabetes. The worldwide prevalence and annual incidence of T2DM in children and young people is increasing,1 and the National Paediatric Diabetes Audit (NPDA) of England and Wales from 2019-20 showed a prevalence and incidence of 4.5 and 1.7 per 100 000 people 15 years and younger, respectively, and 222 new diagnoses.2 Over the past three years, prevalence has increased by one third, and many children and young people with T2DM are not currently receiving care from paediatric diabetes teams.3 Children and young people who are living with obesity, are of ethnic minority background, and reside in the most deprived areas of the UK, are at increased risk of having T2DM.4
In May 2023, the National Institute for Health and Care Excellence (NICE) published its updated guideline on diagnosis and management of T2DM in children and young people, which was updated in 2015 and again in 2022.5 Evidence for this latest update was reviewed in part to align it with current recommendations for adults with T2DM.6 This updated guideline includes recommendations to offer realtime continuous glucose monitoring to children and young people with T2DM who meet specific criteria. It also expands the range of medications recommended in the management of T2DM in children and young people from metformin and insulin to now include the use of liraglutide, dulaglutide, and empagliflozin. In this article, we have selected the most pertinent recommendations for primary care practitioners. The full recommendations are available on the NICE website.5
Recommendations
NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italics in square brackets. Definitions of evidence certainty are given in box 1.
GRADE Working Group grades of evidence
High certainty—we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty—we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty—our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low certainty—we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
At diagnosis
The guideline committee has recommended that all children and young people with suspected or confirmed T2DM be referred by their GP practice to secondary care (a specialist paediatric diabetes clinic) to be managed by a multidisciplinary team. This is to ensure appropriate diagnosis, immediate and continuing treatment, and access to additional essential services such as telephone or mental health support. Although the focus of the guideline was on glucose lowering treatments, the mainstay of management of T2DM includes a continuing programme of education from diagnosis, including information on weight management programmes, which include strategies to increase physical activity, improve eating behaviours and the quality of diet, and reduce energy intake. NICE’s recently updated guideline on identifying, assessing, and managing obesity provides relevant non-medical management recommendations.7
Capillary blood glucose monitoring is now recommended for all children and young people with T2DM. Although this has been happening in practice for some time, the new guidance makes explicit the need to provide equipment for capillary blood glucose monitoring from the time of diagnosis. As some capillary blood test meters allow glucose data to be uploaded or shared online, one aim of the recommendation is for people to share their results with healthcare professionals on a regular basis, enabling them to make timely and better informed treatment recommendations. Some people may be eligible for continuous blood glucose monitoring from diagnosis, and the guideline committee has made a separate recommendation regarding them.
In children or young people with suspected T2DM who present with an HbA1c level of ≥69 mmol/mol (≥8.5%), or it is clinically uncertain whether the person has T2DM or type 1 diabetes mellitus (T1DM), urgent further assessment is warranted by the specialist paediatric diabetes team. This is because of the risk of developing diabetic ketoacidosis or hyperosmolar hyperglycaemic state in people with severe hyperglycaemia.
Refer children and young people with suspected T2DM to a multidisciplinary paediatric diabetes team for specialist review to:
Confirm diagnosis and
Provide immediate and continuing care.
Offer children and young people with T2DM:
Advice and support on dietary management
A metformin monotherapy formulation in line with their own preferences
Equipment for capillary blood glucose monitoring.
In addition, offer children and young people with T2DM:
Insulin if their HbA1c level is 69 mmol/mol (8.5%) or more
Basal-bolus insulin if they have ketosis but not diabetic ketoacidosis.
[Based on the experience and opinion of the Guideline Development Group]
Monitoring blood glucose levels and reviewing treatment
In children and young people with a new diagnosis of T2DM and starting treatment with metformin, the guideline committee has updated its 2015 recommendations to review their glucose monitoring data at four weeks, instead of initially at three months. This is because this group of children requires early review to assess current treatment and escalate it if plasma glucose concentrations are not yet in target or reduce insulin treatment if glucose levels are in target.
This recommendation aims to avoid treatment inertia, staying on a treatment with the associated increased risk of experiencing side effects (potentially hypoglycaemia or weight gain) or when it is not sufficiently effective (potentially leading to hyperglycaemia). Earlier clinical review can also identify the need for early support of children and young people because of their young age, the high prevalence of complex needs, disease burden, and need for education (in young people and their families) on diabetes and its treatment.
Four weeks after diagnosing T2DM and starting metformin in a child or young person, review data from glucose monitoring and, if needed, change treatment.
Review treatment for children and young people with T2DM, as needed, at least every three months. Assess glucose trends using available data from glucose monitoring and HbA1c measurements.
If HbA1c monitoring cannot be used because of disturbed erythrocyte turnover or abnormal haemoglobin type, estimate trends in blood glucose levels using one of the following:
Glucose profiles
Total glycated haemoglobin estimation (if abnormal haemoglobins)
Fructosamine estimation.
Adjust the frequency of capillary blood glucose monitoring based on the person’s treatment and whether they are using continuous glucose monitoring. Ensure they have enough test strips for capillary blood glucose monitoring.
[Based on the experience and opinion of the Guideline Development Group]
Continuous glucose monitoring
These recommendations are new and are largely based on the 2022 recommendations for the use of continuous glucose monitoring in children and young people with T1DM.5
Offer realtime continued glucose monitoring to children and young people with T2DM if any of the following apply. They:
Have a need, condition, or disability (including a mental health need, learning disability or cognitive impairment) that means they cannot engage in monitoring their glucose levels by capillary blood glucose monitoring
Would otherwise be advised to self-monitor at least eight times a day
Have recurrent or severe hypoglycaemia.
Consider realtime continuous glucose monitoring (rtCGM) for children and young people with T2DM who are on insulin therapy.
Consider intermittently scanned continuous glucose monitoring (isCGM, commonly referred to as “flash”) for children and young people with T2DM aged 4 and over who are on insulin therapy if:
rtCGM is contraindicated for them or
They express a clear preference for isCGM.
When offering continuous glucose monitoring to children and young people with T2DM, choose the appropriate device with them, based on their individual preferences, needs, characteristics, and the functionality of the devices available. See full guideline for factors to consider in discussion.
When choosing a device for continuous glucose monitoring, if multiple devices meet the person’s needs and preferences, offer the device with the lowest cost.
Commissioners, providers, and healthcare professionals should address inequalities in access to and uptake of continuous glucose monitoring by:
Monitoring who is using continuous glucose monitoring
Identifying groups who are eligible but have a lower uptake
Making plans to engage with these groups to encourage them to consider continuous glucose monitoring.
[Based on the experience and opinion of the Guideline Development Group]
Adding liraglutide, dulaglutide, or empagliflozin
Prior to this update, only insulin was recommended for use with metformin to lower blood glucose concentrations. The new recommendations now include the addition of three glucose lowering agents that can be used in combination with metformin when glucose concentrations have not responded sufficiently to metformin monotherapy: the GLP-1 receptor agonists liraglutide and dulaglutide (a once daily and a once weekly subcutaneous injection, respectively) and the SGLT2 inhibitor empaglifozin (a once daily oral tablet).8910 These provide children and young people with T2DM and their healthcare professionals with a choice of treatments and modes of administration.
In placebo controlled trials, metformin combination therapy with these agents provided clinical benefit. In the short term (26 weeks), compared with placebo, liraglutide, dulaglutide and empagliflozin were effective at reducing HbA1c % in children and young people with T2DM: mean difference liraglutide: -1.06 (95% confidence interval, CI -1.66 to -0.46) dulaglutide: -1.4% (95% CI -1.95 to -0.85); empagliflozin: -0.84% (95% CI -1.49 to -0.19).8910 Reductions were also seen for scores of mean fasting plasma glucose across all three drugs. Only the liraglutide trial reported long term data (54 weeks) and showed that the reductions in these outcomes were maintained (HbA1c %: mean difference -1.3% (95% CI -1.73 to -0.87); mean fasting plasma glucose difference: -1.81 mmol/L (95% CI, -2.54 to -1.08), although there was a greater than twofold increased risk of nausea and vomiting.10
Because of the specific increased risks of hypoglycaemia and weight gain associated with insulin therapy, separate recommendations for the addition of liraglutide, dulaglutide, or empagliflozin as combination therapy with insulin were made regarding when to add (if not on insulin) or when to reduce or stop it (if already on it).
As of June 2023, two of the newly recommended glucose lowering agents (dulaglutide and empagliflozin) were not yet licensed for use in the UK paediatric population. However, the guideline committee agreed that the lack of additional treatment options for children and young people with T2DM justified their inclusion in the updated guidelines.
People on metformin only
Offer liraglutide or dulaglutide, depending on the person’s preference, in addition to metformin, to children and young people aged 10 or over with T2DM if they have:
an HbA1c level of more than 48 mmol/mol (6.5%) or
a plasma glucose level of more than 7 mmol/litre, on four or more days a week, when fasting or before meals or
a plasma glucose level of more than 9 mmol/litre, on four or more days a week, two hours after meals.
Consider empagliflozin, in addition to metformin, for children and young people aged 10 or over with T2DM who:
Meet any of the criteria listed in recommendation 1.3.49
Are not able to tolerate liraglutide or dulaglutide or have a clear preference for empagliflozin.
[Based on low to high quality evidence from randomised controlled trials]
Implementation
Compared with the adult population, the number of children and young people with T2DM in England is small (1560 under age 19 as of 2019-20). Prevalence is anticipated to increase, especially given the increasing number of children and young people who are overweight or living with obesity between the ages of 4 and 114). No formal health economic analysis was performed during this update.
Specialist teams managing T2DM in children and young people will need to gain familiarity with the newly recommended glucose lowering agents and arrange appropriate support for people and their families to access continuous glucose monitoring devices. Given the significant proportion of children and young people with T2DM who are not under specialist care, GP practices may consider systematically identifying registered children and young people with known T2DM who are not under such care to offer a referral and support as appropriate.
Future research
Long term, what is the effectiveness of liraglutide, dulaglutide, or empagliflozin in children and young people with T2DM?
In children and young people with T2DM, what is the effectiveness of glucose lowering agents currently used (eg, dipeptidyl peptidase IV inhibitors, sodium-glucose cotransporter-2 inhibitors) to manage blood glucose levels in adults with type 2 diabetes?
Guidelines into practice
Primary care
What processes do you have in place to identify children and young people with T2DM who are registered with your practice but who are not receiving specialist care?
What might prompt you to make a same-day referral for a young person with hyperglycaemia (whether due to T1DM or T2DM) to a specialist diabetes team?
Specialist services
What training or support needs does your specialist service have in relation to the use of GLP-1 receptor agonists and SGLT2 inhibitors in children and young people with T2DM?
Further information on the guidance
Diabetes (type 1 and type 2) in children and young people: diagnosis and management guideline is available at https://www.nice.org.uk/guidance/ng18. The evidence review for glucose lowering agents is available at https://www.nice.org.uk/guidance/ng18/evidence and the resource impact statement at https://www.nice.org.uk/guidance/ng18/resources/resource-impact-statement-glucoselowering-agents-for-type-2-diabetes-13060980397.
This guidance was developed by NICE’s Guideline Development Team B in accordance with NICE guideline development methods (www.nice.org.uk/media/default/about/what-we-do/our-programmes/developing-nice-guidelines-the-manual.pdf). A guideline committee (GC) was established by NICE’s Guideline Development Team B, which incorporated healthcare and allied healthcare professionals (three consultant paediatricians with an interest in diabetes, two paediatric diabetes nurse specialists, two pharmacists, two GPs, one consultant diabetologist) and two lay members.
The guideline is available at https://www.nice.org.uk/guidance/ng18.
The GC identified relevant review questions and collected and appraised clinical and cost effectiveness evidence. Quality ratings of the evidence were based on GRADE methodology (www.gradeworkinggroup.org). These relate to the quality of the available evidence for assessed outcomes or themes rather than the quality of the study. The GC agreed recommendations for clinical practice based on the available evidence or, when evidence was not found, based on their experience and opinion using informal consensus methods.
The scope and the draft of the guideline went through a rigorous reviewing process, and stakeholder organisations were invited to comment on the draft of the guideline, the evidence review, and the equality and health inequalities impact assessment; the GC took all comments into consideration when producing the final version of the guideline.
NICE will conduct regular reviews after publication of the guidance, to determine whether the evidence base has progressed significantly enough to alter the current guideline recommendations and require an update.
How people with T2DM were involved in the creation of this article
Committee members involved in this guideline update included lay members who contributed to the formulation of the recommendations summarised here.
Footnotes
The members of the Guideline Committee were (shown alphabetically):
Juliana Chizo Agwu, Nivedita Aswani, Chirag Bakhai, Neel Basudev, Gemma Currie, Carole Gelder, Evelien Gevers, Fasahat Hussain (lay member), Nifemi Iyekowa (lay member), Natasha Jacques, Sallianne Kavanagh, Paul Lincoln (chair), Carol Metcalfe. The technical members of the Guideline Development Team were Stephanie Armstrong, Linyun Fou, Syed Mohiuddin, and Caroline Mulvihill.
Contributors: All authors contributed to the development of the guideline and to the planning, drafting, and revision of this summary, approved the final version, and take responsibility for its accuracy. LF acts as guarantor. The corresponding authors attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
The guideline referred to in this article was produced by the National Institute for Health and Care Excellence (NICE). The views expressed in this article are those of the authors and not necessarily those of NICE.
National Institute for Health and Care Excellence (2023) Diabetes (type 1 and 2) in children and young people: diagnosis and management. Available from https://www.nice.org.uk/guidance/ng18
Funding: LF is an employee of NICE. Other authors received no specific funding to write this summary. This work was undertaken by LF which received funding from the National Institute for Health and Care Excellence. The views expressed in this publication are those of the authors and not necessarily those of NICE
Competing interests: We declared the following interests based on NICE’s policy on conflicts of interests (https://www.nice.org.uk/Media/Default/About/Who-we-are/Policies-and-procedures/declaration-of-interests-policy.pdf): No conflicts of interest were declared. The guideline authors’ full statements can be viewed at https://www.nice.org.uk/guidance/ng18/update/ng18-update-4/documents/register-of-interests.
Provenance and peer review: commissioned, not externally peer reviewed.