Rationale and impact
These sections briefly explain why the committee made the recommendations and how they might affect practice.
The evidence on real-time continuous glucose monitoring (rtCGM) showed it leads to:
a decrease in HbA1c and
an increase in time in range.
This reflected the committee's experience in clinical practice. They highlighted that the continuous nature of rtCGM, and the fact that it can be connected to the phone or device of a parent or carer so they can track the data, were particularly important components for children and young people.
Because the evidence showed similar benefits of rtCGM for children and young people as for adults, the committee extrapolated the cost-effectiveness results from adults, concluding that rtCGM was cost effective in this population.
The committee agreed that children and young people needed support to understand how continuous glucose monitoring (CGM) works, the accuracy of devices and the benefits it can provide, so they emphasised that rtCGM should be provided along with education on how to use it.
Intermittently scanned CGM (isCGM) had no clinically meaningful effect on any of the outcomes that were looked at in the evidence. In the committee's experience, the intermittent nature of isCGM can affect adherence in children and young people.
Since the same clinical benefits were not found for isCGM in children and young people as in adults, the committee agreed those cost-effectiveness findings could not be extrapolated, so they could not conclude that isCGM is a cost-effective technology for the full population of children and young people. They therefore agreed that isCGM should be restricted to children and young people who are unable or do not want to use rtCGM, or who would prefer isCGM. Children and young people who prefer isCGM are likely to have better adherence with this type of device, so it would provide more benefit. The recommendation limits isCGM to children aged 4 and over because no isCGM devices are licensed in children under 4.
The committee did not make a recommendation on using specific devices because CGM technologies are changing very quickly and this recommendation would soon be out of date. Local healthcare services are better placed to assess which devices are evidence-based and suitable for use at any given time.
The committee wanted to highlight the importance of providing choice between the different CGM devices because the best device for each person would vary, so they produced a list of what to consider when discussing this with children and young people.
CGM should also be included in the continuing programme of education that children and young people with type 1 diabetes are offered. This will increase the likelihood that people will scan and report the results frequently, allowing them to understand and manage their diabetes effectively. In addition, children and young people should be supported by a team with expertise in using CGM. This will help them to use the technology effectively to manage their diabetes.
The committee made the recommendation about discussing possible problems with children and young people who are not using their device 70% of the time because it is important that the CGM device is used for a significant proportion of time for it to have a positive effect. They wanted to avoid a child or young person feeling 'punished' for using it less than that, but agreed that less than 70% use should trigger a discussion to find out if extra support is needed. While they did not make recommendations on stopping CGM, the committee acknowledged that it may not be offered as a permanent solution and that it can be stopped if it is not being used effectively or not perceived to be providing enough benefit.
Despite the positive recommendations on CGM, the committee were concerned that existing health inequalities may still lead to lower uptake of CGM in some groups of people. To address this, the committee made a recommendation outlining actions for commissioners, providers and healthcare professionals.
One of the known factors determining the use of CGM devices among children and young people with type 1 diabetes is sensitivities to the device, such as local skin reactions to the adhesive used in the sensor. The committee agreed that research is needed to investigate strategies to reduce local skin reactions to promote ease of use and adherence of these devices, so they made a recommendation for research on continuous glucose monitor sensor adhesive to prevent sensitivities.
The committee also made a recommendation for research using routinely collected real-world data to examine the effectiveness and cost effectiveness of CGM. They agreed that this has the potential to show the direct effects of implemented technology in children and young people instead of interpreting it through the results of clinical trials. Increased monitoring of routine healthcare data including registries and audits would ensure the findings from a broader population is captured.
These recommendations are likely to result in broader access to rtCGM and isCGM devices for children and young people. This will increase costs but should reduce inequalities and enable more people to access the technology. Currently, children and young people, and their parents and carers, who have more time and knowledge to advocate or self-advocate are often more likely to gain access to these devices.
Some children and young people have insulin insufficiency because of other conditions. The committee noted that these children and young people would get the same care as children and young people with type 1 diabetes, so they should have access to CGM.
There was no evidence for children and young people, so the committee extrapolated from the evidence for adults with type 1 and type 2 diabetes. There was a lot of consistent evidence showing that adults with diabetes are at increased risk of periodontitis and that non-surgical treatment can improve diabetic control. The clinical and cost effectiveness of periodontal treatment in adults were sufficient to justify the recommendations for children and young people with diabetes.
Children and young people with diabetes are at increased risk of developing periodontitis. However, in the committee's experience, they are often unaware of this and may not be having regular oral health reviews. To address this, the committee recommended routinely discussing the risk of periodontitis at the child or young person's regular diabetes reviews, alongside eye disease and foot problems.
Oral hygiene and the need for regular oral health reviews has been added to the standard education children and young people with diabetes should receive, because this will help them prevent periodontitis.
For oral healthcare professionals, the long-term impact of the recommendations is uncertain. The recommendations specify that people should follow existing NICE guidelines on oral health. However, the recommendations may also increase awareness of periodontitis, leading to a possible short-term increase in the number of oral health reviews. Any increase in the number of oral health reviews will potentially impact on services as NHS dental services already have capacity issues.
A short-term increase in the number of oral health reviews will also lead to a short-term increase in costs. However, there is likely to be a larger long-term reduction in costs from the improvement to oral health and diabetes control.
Oral healthcare and dental teams will need clear advice on what they need to do for people with diabetes. They will need clear care pathways to improve quality of care and service delivery, in line with the NHS England commissioning standard on dental care for people with diabetes.
NHS dental services are free for children and young people under 18, although not everyone makes use of this. The recommendations may encourage more children and young people with diabetes to have regular oral health reviews. Combined with proactive engagement and enhanced support for children and young people with diabetes, this may broaden access to dental and oral healthcare and help to reduce oral health inequalities.
Glucose-lowering agents for managing blood glucose levels in children and young people with type 2 diabetes
lifestyle changes (for example, diet and exercise)
blood glucose monitoring and
The committee made recommendations to provide information and education to support all 3.
They also made 3 further recommendations about education and information. They agreed that:
Insulin therapy to manage blood glucose levels is a complicated and demanding treatment. Children and young people with type 2 diabetes should be given the opportunity to learn about it so that they can more effectively manage their disease.
Information should be provided in a way that takes the specific needs and preferences of children and young people with type 2 diabetes into account and supports shared decision making.
Information and education about CGM for those receiving insulin or who are in specific groups should be part of a continuing programme of education because it is likely that they will use it at least once during the course of their lives.
The recommendations are not expected to substantially affect practice.
In the committee's experience, children and young people with type 2 diabetes are sometimes not cared for by a multidisciplinary team, in a specialist paediatric diabetes clinic. When this is the case, the child or young person is not able to access additional essential services such as telephone or mental health support. The committee therefore made a recommendation to ensure equal access to paediatric diabetes services for all children and young people with type 2 diabetes.
Various formulations of metformin are available, but only the standard-release tablets are licensed for use in a paediatric population. As of April 2023, use of other formulations would be off-label. However, the committee left the choice of metformin monotherapy formulation open on the basis that:
alternative formulations may be more acceptable or better tolerated, and it is common practice for these to be used off-label in such cases
the unit cost per day of modified-release tablets is the same as that of standard-release tablets.
The committee also recommended, using their knowledge and experience, that children and young people with type 2 diabetes should be offered capillary blood glucose monitoring equipment to allow them to monitor their own glucose levels.
The committee agreed, based on their knowledge and experience, that a high HbA1c level at diagnosis justifies adding insulin therapy to metformin to reduce:
blood glucose levels, and therefore reduce the risk of hyperglycaemia
the risk of developing diabetic ketoacidosis (DKA)
the risk of hyperglycaemia-related complications in the long term.
They did not specify which insulin therapy should be used (for example, short-, long-, or intermediate-acting) because they agreed that this choice should be left to the relevant healthcare professional to allow flexibility of treatment.
They also agreed that the presence of ketosis indicates a current insulin deficiency, so a multiple daily (basal-bolus) insulin injection is needed to ensure, as a matter of safety, that DKA does not develop.
The recommendations are not expected to substantially affect practice because dietary management is standard practice. It is also common for different metformin formulations to be used because some children and young people prefer formulations other than the standard-release tablet. Given the relatively small number of children and young people with type 2 diabetes in England and Wales (1,560 in all NHS settings as of 2019/20, according to the NHS Digital report on Young People with type 2 diabetes, 2019-20), the provision of equipment for both capillary blood glucose monitoring and insulin is not expected to have a significant resource impact.
achieve an HbA1c level of 48 mmol/mol (6.5%) or lower as early as possible in the treatment pathway to avoid later complications (such as cardiovascular, kidney and liver disease) and
avoid staying on the same treatment for too long without reassessing its effectiveness.
As a result, they also agreed that current guidance to measure HbA1c levels every 3 months should be retained but supplemented with new recommendations, to make provision for an initial visit earlier than 3 months after diagnosis and for the use of data from capillary blood glucose monitoring or CGM. This is because combining HbA1c and glucose monitoring data will allow seeing trends quicker than changes in HbA1c levels alone.
The target HbA1c level of 48 mmol/mol (6.5%) or lower was chosen because:
it can be used to diagnose type 2 diabetes and
staying below this level is recommended to minimise the risk of long-term complications (see recommendation 1.3.31).
The committee agreed, using their knowledge and experience, that a first visit to review glucose data should take place after 4 weeks of metformin monotherapy. A period of 4 weeks was agreed because:
at least 4 weeks of glucose monitoring data is needed to assess whether glucose levels are improving or whether treatment needs to be escalated
although current guidance is for the first clinical visit to take place 3 months after diagnosis, in practice, this occurs earlier because newly diagnosed children and young people with type 2 diabetes often need more support than those whose glucose levels have already stabilised
for children and young people with type 2 diabetes who are also on insulin therapy, safely reducing and stopping insulin typically takes 2 to 6 weeks, so a review of additional CGM data at 4 weeks will help.
Given the above considerations and the many differences between individual children and young people with type 2 diabetes, the committee agreed that healthcare professionals should carry out subsequent reviews at least every 3 months (the recommended frequency of HbA1c measurements). However, they recognised and allowed for the fact that reviews may be required more often (especially if the child or young person is on insulin therapy).
The committee acknowledged that there are rare cases in which HbA1c measurements cannot be used (for example, when the child or young person has abnormal haemoglobin). Using their knowledge and experience, they recommended 3 alternative methods of estimating average glycaemia for use in such cases.
They also agreed that the frequency of monitoring should be based on several factors:
For example, children and young people with type 2 diabetes who are on insulin but not using CGM will need to test their capillary blood glucose 4 to 5 times a day while those using insulin and CGM will not need to test it so often. As blood glucose levels stabilise, frequency of capillary blood glucose monitoring can be reduced. Given these considerations, enough test strips should be prescribed to enable the person to self-monitor as required by their treatment until the next review.
The recommendations on capillary blood glucose monitoring and an initial review 4 weeks after diagnosis reflect current practice in England and therefore are not expected to have a significant impact.
CGM is already recommended for everyone with type 1 diabetes and in some adults with type 2 diabetes, and the committee agreed that children and young people with type 2 diabetes should be offered the same.
The committee's decision to include these recommendations was also based on the following:
Type 2 diabetes in children and young people is the most aggressive form of the disease, and this population will live with the condition for longer than adults with type 2 diabetes, so timely intervention is important to reduce the risk of developing severe long-term (and possibly life-threatening) complications, such as peripheral neuropathy.
Many children and young people experience health inequalities because of comorbidities (for example, special educational needs or learning disabilities), which can make it difficult for them to conduct capillary blood glucose measurements.
Capillary blood glucose monitoring often requires several finger-prick tests a day, which can be tiring, stressful and have a negative psychological impact on the person. CGM provides another, less invasive way for children and young people with diabetes to manage their blood glucose levels.
Some CGM devices allow glucose data to be shared electronically.
Using CGM, even in the short term, is likely to improve the child or young person's understanding of their own blood glucose patterns because of the continuous and visual way CGM allows glucose data to be presented.
The evidence base for the effectiveness of CGM in this population is limited, mostly because of the small number of children and young people with type 2 diabetes. As a result, the committee based recommendations on CGM for this population on the recommendations about CGM for children and young people with type 1 diabetes, in this guideline, and on the recommendations about CGM for adults in NICE's guideline on type 2 diabetes in adults.
The 2022 evidence review on the effectiveness of CGM to improve blood glucose level management in children and young people with type 1 diabetes concluded that:
rtCGM is more effective than capillary blood glucose monitoring
isCGM is no more effective than capillary blood glucose monitoring.
Therefore, the committee agreed that rtCGM should be considered when children and young people with type 2 diabetes are on insulin therapy because of:
the increased risk of hypoglycaemia
comorbidities associated with type 2 diabetes in children and young people and
the decreasing costs over time of available and appropriate devices.
As for adults, the committee agreed that CGM should not be considered for all children and young people with type 2 diabetes because some will be able to maintain their blood glucose levels within the target range using glucose-lowering agents that do not increase the risk of hypoglycaemia (such as metformin monotherapy).
The option to consider isCGM for people over 4 years old was provided because:
some children and young people with type 2 diabetes have difficulties using rtCGM or may prefer isCGM to rtCGM
in May 2023, isCGM was licensed for children aged 4 years and over.
The committee agreed that a stronger recommendation to offer rtCGM to 3 specific groups was justified, regardless of whether they are having insulin therapy, because of the child or young person's individual needs and the treatment burden associated with capillary blood glucose monitoring.
Regardless of the reason the child or young person with type 2 diabetes is offered CGM, the committee agreed that it should be provided by a team with expertise in its use, so that support can be provided and any issues with it can be quickly resolved.
The committee agreed that CGM should not replace capillary blood glucose monitoring because it is still needed both for checking the CGM device and as a back-up. They made some further recommendations about choosing and using a CGM device to encourage adherence and provide support.
Finally, the committee agreed, in line with the recommendations for children and young people with type 1 diabetes, that inequalities in access and uptake of CGM may still occur for those with type 2 diabetes, so they added a recommendation to address this. For example, obesity and type 2 diabetes are also closely associated, as are childhood obesity and socioeconomic status (it is highest among children living in the most deprived areas).
The availability of devices for rtCGM or isCGM that allow remote sharing of data is increasing, although there can be wide variation in their cost. Some children or young people will also not have access to a mobile phone or compatible electronic device, which the CGM devices may require, so some provision for this may be needed. However, the number of children and young people with type 2 diabetes who will be eligible for CGM will also be relatively low. So, the recommendations to consider or offer CGM is unlikely to have a significant resource impact.
The committee recognised that insulin use substantively increases the risk of hypoglycaemia and weight gain and that it should be gradually reduced and stopped when the person's HbA1c levels is under the 48 mmol/mol (6.5%) threshold. They agreed 3 criteria for when to reduce insulin use, based on those recommended for type 1 diabetes (see recommendation 1.2.55).
The committee also recognised that the choice of how often glucose levels could exceed the target ranges was somewhat arbitrary, but they were keen to avoid basing decisions on single events and agreed that having low glucose levels more often than not (for example, on 4 or more days a week) would certainly indicate that insulin can be reduced.
The committee made separate recommendations about combining metformin with other glucose-lowering agents for children and young people with type 2 diabetes who are or are not on insulin therapy because insulin therapy is associated with specific risks (such as hypoglycaemia) not associated with metformin monotherapy. However, the overall rationale for these recommendations remains broadly the same and any differences relating to insulin therapy will be noted below.
Three thresholds were chosen for when to initiate metformin therapy with liraglutide, dulaglutide, or empagliflozin (rather than insulin) for children and young people with type 2 diabetes. These thresholds reflect the chosen HbA1c threshold and upper limits of the blood glucose target ranges in recommendation 1.3.48.
Overall, the evidence showed that 2 GLP-1 receptor agonists, liraglutide and dulaglutide, and one SGLT2 inhibitor, empagliflozin, were generally effective in the short term at reducing glucose levels in children and young people with type 2 diabetes. Liraglutide and dulaglutide had significant effects on the majority of critical outcomes, including change in HbA1c level, mean fasting plasma glucose level, and use of insulin rescue medication. Empagliflozin also had significant effects on change in HbA1c percentage level and mean fasting plasma glucose level. No difference on the important outcomes (serious adverse events, gastrointestinal symptoms) was found in the short term.
Only one trial reported long-term data, comparing liraglutide to placebo, which showed that its effectiveness for managing blood glucose levels was maintained after 52 weeks. However, there was an increased risk of nausea and vomiting.
Though the recommendations mean potentially combining dulaglutide, liraglutide or empagliflozin with metformin earlier than it would be combined for an adult, the committee agreed it is justified by the relatively small number of available treatments for the paediatric population and the risks associated with:
not achieving an HbA1c level of 48 mmol/mol (6.5%) or lower, and
developing complications related to diabetes.
The restriction to children and young people aged 10 years or over reflects the licensing conditions for liraglutide.
The weaker strength of recommendation for empagliflozin reflects the evidence, suggesting that it is slightly less effective at managing blood glucose levels than liraglutide and dulaglutide, although there was no direct evidence comparing any of these agents to each other.
The committee also agreed that the lowest dose of liraglutide, dulaglutide, and empagliflozin needed to maintain the target ranges specified in recommendation 1.3.48 should be maintained. This is because higher doses can lead to side effects and poorer treatment adherence. The committee also agreed, using their experience, that a specific warning about the use of empagliflozin was needed because its use as a glucose-lowering agent in the paediatric population is relatively recent.
Insulin use is associated with an increased risk of hypoglycaemia and weight gain. Given this, the committee recommended that, for children and young people with type 2 diabetes on metformin only, insulin should only be offered when other treatments have failed to stabilise glucose levels.
Similarly, the committee agreed that, for children and young people with type 2 diabetes who are on both metformin and insulin, insulin should only be increased when adding other treatments has failed to stabilise glucose levels. However, the committee recognised that there may be some children and young people with type 2 diabetes in whom other treatments (that is, liraglutide, dulaglutide or empagliflozin) may be contraindicated or not tolerated. The committee agreed that this should not prevent increasing their insulin dose and added a specific provision in the criteria to account for this.
The committee also discussed whether body mass index should be a criterion for starting treatment with glucose-lowering agents – as it is for adults – but decided that this was not needed because a small proportion of children and young people with type 2 diabetes are not overweight and specifying such a criterion would exclude this group from treatment.
Dulaglutide is administered as a weekly injection, whereas liraglutide requires daily injections. Empagliflozin is an oral (tablet) treatment. Because some children and young people may prefer 1 treatment regimen over the other, the committee agreed to recommend both liraglutide and dulaglutide injections and, if contraindicated, oral empagliflozin, even though:
The committee recognised that they did not have direct evidence comparing the effectiveness of weekly treatments compared to daily treatments with glucose-lowering agents for managing blood glucose levels. So, they made a research recommendation to:
There are a lot of medicines that can be used to manage blood glucose levels in adults with type 2 diabetes. In contrast, there are very few licensed, effective and safe medicines to manage blood glucose levels for children and young people with type 2 diabetes. The committee thus made a research recommendation for further clinical trials in children and young people of medicines used for adults.
As of April 2023, there are 4 other medicines that are licensed for use in the UK in a paediatric population:
exenatide (a GLP-1 receptor agonist)
dapagliflozin (an SGLT2 inhibitor)
insulin detemir (a long-acting insulin)
neutral protamine Hagedorn (NPH) insulin (an intermediate-acting insulin).
The committee agreed that the evidence was not sufficient for either of the first 2 licensed medicines to be recommended, nor for one insulin to be recommended over the other.
Liraglutide and dulaglutide are relatively expensive compared to other possible treatments but recommending them is unlikely to surpass NICE's £1 million threshold for significant resource impact. Empagliflozin is approximately half the price of both liraglutide and dulaglutide. However, there was insufficient evidence to construct a full cost-effectiveness model. The committee indicated that the difference in unit cost per dose is relatively small, especially when considering the low prevalence of type 2 diabetes in children and young people. Similar considerations apply to using insulin at diagnosis where the prevalence of type 2 diabetes combined with a high HbA1c level or high blood ketones is even lower.
Increased support from a paediatric diabetic nurse and consultant will be needed when the child or young person starts on liraglutide, dulaglutide or empagliflozin. However, once the child or young person's HbA1c levels are stabilised, this will no longer be required because repeat prescriptions can be made by the GP.
Insulin is a last resort in the management of type 2 diabetes in children and young people and the recommendations are not expected to substantially affect practice.
The committee based their recommendations on insulin therapy on those for children and young people with type 1 diabetes. Overall, the committee agreed that the choice of insulin therapy should be left to the child or young person with type 2 diabetes (or their families or carers), in consultation with the specialist diabetes paediatric team. The committee made some general recommendations about choosing an insulin regimen, providing appropriate equipment for injections, reviewing injection sites, and providing additional support when their glucose levels are not optimal.
Insulin is a last resort in the management of type 2 diabetes in children and young people and the recommendations are not expected to substantially affect practice.
The committee agreed that the paediatric diabetes team should update the child or young person's school healthcare plan annually, and when treatment changes in a way that affects the child or young person while they are at school. This will enable coordination of care with the child's or young person's school.
The recommendation is not expected to substantially affect practice.
The 2015 recommendations caused some confusion around when to use oral or intravenous fluids. To address this, the committee looked for research evidence that would help them make clearer recommendations. There was no evidence that compared different routes of administration or different oral fluids for hydration, so the committee updated the recommendations based on their experience and expertise.
In the 2015 guideline, the rate of fluid administration in DKA was restricted because rapid fluid administration was believed to cause cerebral oedema. However, for the 2020 update there was some randomised controlled trial evidence (particularly the PECARN FLUID trial) comparing the effect of different DKA protocols on outcomes such as mortality or clinically apparent brain injury. This evidence showed no significant difference between the 2 protocols, and it demonstrated that the restrictions on the rate of fluid administration were not needed.
In response to this evidence, and applying their clinical expertise, the committee updated the recommendations to use more rapid fluid administration (including fluid boluses). They also made a separate recommendation for children and young people who are in shock, as this group need a higher volume of fluids and they need these fluids to be given more rapidly.
When the 2015 recommendations were made, rapid fluid administration was believed to cause cerebral oedema. However, more recent randomised controlled trial evidence (particularly the PECARN FLUID trial) has shown that brain injury in this group may be caused by DKA itself because of the resulting cerebral hypoperfusion, reperfusion and neuro-inflammation. If DKA is the cause of brain injury, children and young people would benefit from receiving more fluids in the first 48 hours than was recommended in the 2015 guideline. To address this, the committee updated the recommendation on calculating the fluid maintenance requirement, based on their clinical knowledge and on evidence from the PECARN FLUID trial. The Holliday–Segar formula that they recommended is commonly used in practice and has not been shown to cause any adverse events.
No evidence was identified on the use of potassium. The committee used their expertise and their understanding of the evidence on the pathophysiology of DKA to update the recommendation. They added more detail about how to care for children and young people with anuria or potassium levels above the normal range. It is essential to not delay adding potassium to fluids because insulin can cause hypokalaemia in this population, which can lead to cardiac arrhythmias and death.
The committee also used their expertise to make recommendations highlighting complications such as hyperchloremic acidosis.
There is variation in practice due to the different beliefs on the causes of cerebral oedema. The new recommendations will be a change in practice in some areas, but they are in line with randomised trial evidence and with other clinical guidance (such as chapter 11 in the 2018 International Society for Paediatric and Adolescent Diabetes DKA guideline).