Abstract
Continuous glucose monitoring (CGM) is now advocated for the clinical management of individuals with type 1 diabetes (T1D). However, this glucose monitoring strategy is not routinely used in type 2 diabetes (T2D), given the large population, significant cost implications and relatively limited supporting evidence. T2D is a more heterogenous condition compared with T1D with various glucose lowering therapies that do not necessarily require CGM to ensure within target glucose levels. While all individuals with T2D may benefit from CGM at certain time points, the whole T2D population does not necessarily require this technology continuously, which should be prioritized based on patient benefit and cost effectiveness. In this pragmatic opinion piece, we describe the rationale and evidence for CGM use in different subgroups of individuals with T2d, divided according to the stage of the condition, glycemic therapies, presence of diabetes complications, or associated co-morbidities. We discuss a total of 16 T2D subgroups and provide a clinical view on CGM use in each, based on current evidence while also highlighting areas of knowledge gaps. This work provides health care professionals with a simple guide to CGM use in different T2D groups and gives suggestion for future studies to justify expansion of this technology.
Avoid common mistakes on your manuscript.
Continuous glucose monitoring (CGM) is recommended for the management of all individuals with type 1 diabetes but use in type 2 diabetes (T2D) is more limited. |
Individuals with T2D represent a heterogenous group of people with vastly different glucose profiles, dependent on stage of the condition, glycemic therapies, and associated co-morbidities. |
Studies to date generally support the use of CGM in individuals with T2D on insulin therapies and limited work also demonstrates potential benefits in non-insulin users. |
CGM appears to be useful in individuals with T2D and associated complications, including advanced renal disease and recent myocardial infarction. |
More research is needed to understand the role of CGM in modulating hard clinical outcomes in different T2D groups, including individuals with early micro/macrovascular disease, as well as those with associated conditions, such as cancer, psychiatric disorders, long-term disabilities, and during hospital admissions for any cause. |
Introduction
Diabetes is a global health condition with the numbers affected rising at an alarming pace. In 2021, there were 537 million individuals with diabetes worldwide, which is expected to reach 783 million by 2045 with the majority (around 90%) having type 2 diabetes (T2D) [1].
Studies have shown that glycated hemoglobin (HbA1c), reduces the risk of microvascular disease and long-term macrovascular complications in T2D [2], which has also been the case for individuals with T1D [3, 4]. Given the association with diabetes complications, HbA1c has been a key glycemic marker that guides diabetes management. However, relying solely on HbA1c can be problematic, as it can be inaccurate in some patients such as those with anemia, hemoglobinopathies, and renal failure, while some therapies can also affect accuracy of this marker [5]. Moreover, response of HbA1c to therapeutic interventions is usually delayed and therefore failure of a particular management strategy can take months to become apparent [6], which is a concern when rapid improvement in glycemia is required. Importantly, HbA1c does not give information on treatment-induced hypoglycemia, which is known to be associated with adverse outcomes [7, 8], particularly in older individuals.
Given the shortfalls of HbA1c and its inability to address within day changes in glucose profile, self-monitoring of blood glucose (SMBG) has been an essential complementary glucose monitoring strategy, particularly for those on insulin therapies [9, 10]. However, SMBG can cause significant discomfort and needs to be performed regularly in order to make effective management decisions, which can be inconvenient to patients. More recently, however, continuous glucose monitoring (CGM) has been used to adjust insulin therapies and this has revolutionized glycemic management in diabetes [11]. There are different CGM devices; blinded CGM does not allow the individual with diabetes to see glucose data in real time, which are usually reviewed retrospectively by the diabetes care provider to adjust therapies. The more popular unblinded CGM data can be accessed in real time (rtCGM) or following glucose checks in intermittently scanned CGM (isCGM), also known as flash glucose monitoring. For simplicity, we will refer to rtCGM and isCGM as one entity (CGM).
CGM use has mainly focused on the type 1 diabetes (T1D) population in whom such a technology offers clear benefits [12,13,14,15], allowing changes in insulin to be done safely and effectively. CGM has been spreading to individuals with T2D but unlike those with T1D, this is a much larger and heterogeneous population, thus more understanding is required as to the characteristics of patients with T2D who would benefit the most from this technology.
It can be argued that all individuals with T2D stand to benefit from CGM, even if used periodically, as the comprehensive glucose data provided help to better understand the effects of daily life activities and different therapies on glucose profile. However, evidence for CGM benefit in all subgroups of patients with T2D is far from complete and more studies, including cost-effectiveness analysis, are required before recommending this technology to all individuals with T2D. Even in wealthy countries, advocating CGM for all patients with T2D throughout the course of the condition may be difficult, given the large number of these individuals and the significant cost implications. This explains the careful introduction of CGM to the T2D population in most countries, starting with insulin-treated patients [16]. The rationale for initially focusing on this group is clear, given the high risk of metabolic and vascular complications in these individuals and the presence of ample evidence for CGM benefit through reduction in HbA1c and/or limiting hypoglycemia, and improving quality of life measures [17]. However, arguably such an approach is too naïve, as all patients with T2D should benefit from early optimization of glycemia, thus avoiding becoming “high risk” in the first place. A consensus opinion on the use of CGM in non-insulin treated patients with T2D has been recently published [17] and the current opinion piece is a complementary practical guide for health care professionals exploring the use of CGM in different subpopulations of individuals with T2D. To simplify understanding CGM’s role in different subgroups of patients with T2D, we have divided these individuals according to the stage of the condition/type of therapies, presence of diabetes complications, and associated comorbidities.
This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.
The T2D Journey – Role of Different Therapies
The Newly Diagnosed
In the initial stages of T2D, the condition can be managed by altering diet and increasing physical activity without introducing therapeutic agents. However, this is often a progressive condition [18] characterized by worsening HbA1c and soon monotherapy is introduced followed by dual, triple, and even quadruple therapies before necessitating starting insulin. On the other hand, reversal of T2D, and establishment of normoglycemia, has been reported following weight loss secondary to dietary changes or bariatric surgery [19]. Once people with T2D are on insulin, CGM is often considered, particularly when intensive insulin therapies are used given the observed benefits in this group [20,21,22,23]. However, this represents a minority subgroup with the majority “failing to qualify” for CGM as HbA1c, the most widely used measure to assess average glucose levels, is regarded as adequate for monitoring glycemia.
Taking a person with an early diagnosis of diabetes, use of CGM may encourage exercise and healthy eating as individuals can track the effects of daily activities on their glucose levels [24, 25]. There are early indicators of the inability of β-cell to keep up with metabolic demands, leading to raised HbA1c levels and development of T2D. These include high postprandial glucose levels as well as the dawn phenomenon, a physiological process that becomes pathological in diabetes due to deranged insulin function. Dawn phenomenon is driven by hepatic glucose production overnight, which is counterbalanced in people without diabetes by adequate insulin secretion and function. However, insulin resistance in T2D results in excessive elevation of morning fasting glucose and delayed post-breakfast spikes, termed ‘extended dawn phenomenon’ [26]. CGM can aid in defining these abnormal glycemic profiles helping to implement appropriate treatment strategies even at early stages of the condition.
CGM may represent a cost-effective way of managing, and even reversing T2D, but such an approach is not implemented due to the lack of evidence for efficacy. Therefore, randomized controlled trials (RCTs) on the use of CGM in newly diagnosed patients are needed with appropriate health economic analysis. One option to keep the costs manageable is to use CGM intermittently in such individuals, for example once every 2–3 months, but naturally this will need to be supported by appropriate clinical studies to decide the optimal frequency of intermittent use. Targeting this group may delay the introduction of glycemic therapies and has the potential to transform these individuals into an overall healthier population, thus delaying complications and improving quality of life. Limited studies have shown that CGM use can result in lifestyle changes and therefore using CGM to reverse diabetes or delay introduction of therapies is a credible strategy but appropriate studies in this area are lacking.
Monotherapy
After the failure of diet to achieve glycemic targets, or even at diagnosis, monotherapy is started usually with metformin (given the low costs), although other agents can also be used. Given this agent does not cause hypoglycemia, it is not unreasonable to advocate the use of HbA1c for monitoring glycemic response to treatment. However, CGM use can additionally help by altering diet and increasing exercise, as discussed above. While there are studies on CGM use in non-insulin-treated individuals with T2D [27, 28], the subgroup on monotherapy is too small to allow reliable, and adequately powered, separate analysis. Therefore, it remains largely unknown whether CGM use in T2D on monotherapy improves glycemic outcomes.
Multiple Oral Therapies
The same largely applies to T2D groups on dual or multiple non-insulin therapies as those on monotherapy but the type of therapies can also have an impact. Agents in the sulphonylurea (SU) group are rarely used as first line but due to their low cost are frequently prescribed for dual therapy, even in wealthier countries. A key concern with SU is the precipitation of hypoglycemia, which is a particular problem in older individuals who may have reduced hypoglycemic awareness [29] and can be at increased hypoglycemic risk due to associated complications such as renal insufficiency [30]. Indeed, over a quarter of ambulance call outs for severe hypoglycemia in patients with T2D involve non-insulin-treated patients, the vast majority of whom are on sulphonylurea therapies [31]. Moreover, hypoglycemia has been linked to adverse vascular outcome as well as falls resulting in fractures [32,33,34], causing significant morbidity. Therefore, the use of CGM in in sulphonylurea-treated individuals can help the early detection of low glucose levels, particularly at the start of such a therapy. It should be acknowledged that there is a gradual move away from SU to more cardiovascular protective agents such as sodium glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide receptor agonist (GLP-1RA) [8]. However, implementing a stepwise addition of these agents based on HbA1c levels for patients with T2D has been insufficient in clinical practice. To add to the complexity, early combination glycemic therapy represents another new development as this leads to extended periods of within target glucose levels compared with the traditional step-wise approach [35] and may become the preferred treatment modality if cost-effectiveness is proven.
Adapting these insights in clinical practice necessitates timely changes in glycemic management in individuals with T2D. The use of CGM-based goals could serve as supplementary evaluations of treatment effectiveness, particularly given the strong correlation between CGM-derived average glucose and HbA1c levels in individuals with T2D [36].
Insulin Therapies in T2D
RCTs and real-life studies in insulin-treated patients with T2D have shown that CGM is beneficial either through reduction of HbA1c and/or by limiting hypoglycemia and this applies to both multiple daily injections of insulin as well as basal insulin therapies [20,21,22,23]. Admittedly, there is a lack of studies on mixed insulin therapies but their use is limited in most countries and therefore studies targeting such population of patients are unlikely to take place and perhaps are not necessary. Furthermore, outcome data show an association between CGM use and decreased hospitalization for acute diabetes complications, including severe hypoglycemia and ketoacidosis in France, in insulin-treated individuals with T1D as well as in those with T2D treated with insulin and/or non-insulin therapies [37,38,39].
Practical Considerations in the T2D Journey
While appropriately designed CGM studies are required in the newly diagnosed patients with T2D, it is not unreasonable to suggest that CGM is used intermittently in such individuals, regardless of whether they are diet-treated or on monotherapy. This can help with dietary and exercise alterations, provided individuals with diabetes are educated on CGM and the health care professional (HCP) has the necessary experience to interpret the data generated. It is important to regularly assess the effects of CGM and discontinue/continue according to the response and patient engagement. In those with complex non-insulin glycemic therapies, use of CGM will continue to help with implementation and maintenance of lifestyle changes, as part of diabetes self-management, while also monitoring the effectiveness of existing and newly introduced therapies. Moreover, CGM will help in detecting hypoglycemia in SU users and may delay the need for the introduction of insulin. Finally, in insulin-treated patients with T2D, use of CGM has clear benefits and should be considered, regardless of the insulin preparations. Figure 1 summarizes the rationale and evidence for CGM use in individuals with T2D without advanced complications and at different stages of the condition, while Table 1 highlights gaps in knowledge and further studies required.
T2D with Advanced Vascular Complications
Microvascular Disease
In individuals with advanced renal disease, HbA1c becomes unreliable as a measure of glycemia [40, 41]. Moreover, this population is at risk of hypoglycemia and usually experiences large fluctuations in glucose levels due to insulin therapies and/or dialysis required for end-stage renal disease [42, 43]. Therefore, CGM can be particularly helpful in such patients to guide glycemic management and avoid hypoglycemia. Early concerns over CGM inaccuracy in these individuals were unfounded and therefore glycemia in these individuals should be monitored using CGM [44, 45].
In those with advanced retinopathy, optimizing glycemia while avoiding low glucose levels is key and such individuals have the potential to benefit from CGM. However, studies in this population are lacking and, crucially, it is currently unclear whether CGM-guided optimization of glycemia in individuals with advanced retinopathy improves their long-term visual outcomes. However, aiming for within target glucose levels is part of routine clinical practice in these individuals to avoid further deterioration in retinopathy [46] and therefore advocating CGM to preserve sight should be encouraged.
What about the use of CGM in those with neuropathy? There is limited evidence in this group of patients but there is little doubt that those with advanced neuropathy are likely to benefit. Individuals with T2D with autonomic neuropathy experience high glycemic variability [47] and can have gastrointestinal symptoms that make achieving glucose targets problematic, which may be helped by CGM. Moreover, those with autonomic neuropathy may also have significant hypoglycemic unawareness [48], where CGM can be particularly useful if they are on therapies that can result in low glucose levels. Individuals with neuropathy and foot ulcers can develop infective complications [49], which can increase glucose levels and where CGM can be useful to monitor and optimize glycemia, in turn helping with the infective episode and avoiding the need for surgical interventions, including amputation.
Macrovascular Disease
The association between hyperglycemia and adverse cardiac outcome after a coronary event is well known [50]. Studies investigating the effect of improving glycemia on clinical outcome following acute coronary syndrome (ACS) have shown inconsistent findings [51]. The early DIGAMI-1 trial has demonstrated a reduction in mortality with insulin therapy in individuals with ACS [52]. However, it should be noted that DIGAMI-1 was not only about insulin treatment, as it included both glucose and insulin infusion, and therefore it can be argued that it is not a simple “glucose” study. The subsequent DIGAMI-2 trial failed to confirm a role for improved glycemia on outcome in patients with ACS, which may be related to the study being underpowered [53]. However, a more likely explanation is precipitation of hypoglycemia when attempting to reach glucose targets with more aggressive glycemic therapies, a concept supported by observing an association between low glucose levels and adverse outcome in DIGAMI-2. Therefore, it is perfectly plausible that post ACS, a combination of lowering glucose levels while avoiding hypoglycemia is needed to improve clinical outcome. A recent study has shown that CGM use post ACS in individuals with T2D on insulin or sulphonylurea therapy, in addition to any other hypoglycemic treatment, results in reduction in HbA1c by 7 mmol/mol (0.7%) at 3 months, which was similar to the control arm using capillary glucose checks. However, a major difference between study arms was hypoglycemic exposure, which was significantly reduced by CGM use, regardless of whether patients were on insulin or sulphonylurea therapies [54]. Importantly, CGM use in such patients has shown to be cost-effective based on the glycemic data. However, the study was not powered to investigate hard clinical outcomes and a larger study is needed to ascertain the effects of CGM on mortality and morbidity in these patients. This was highlighted as a knowledge gap in the recent ESC cardiovascular guidelines in individuals with diabetes [8].
In acute ischemic stroke, hyperglycemia is common and associated with larger infarct size as well as unfavorable functional outcome, even in those who undergo reperfusion therapy [55,56,57]. In a pilot study, CGM use was shown to be feasible, safe, and accurate in individuals with acute ischemic stroke due to large anterior circulation occlusion and who had undergone complex endovascular therapy [58]. In support of an association between hyperglycemia and stroke, a strong inverse correlation between TIR and carotid intima-media thickness, a proxy for cerebrovascular disease, has been observed [59]. Further studies evaluating the effectiveness of CGM in reducing the risk of stroke in individuals with T2D and improving outcomes following an acute event should be conducted.
Practical Considerations for Patients with T2D with Vascular Complications
In individuals with advanced renal failure, particularly those on dialysis, CGM use has clear benefits and should be considered. While studies are lacking in those with advanced retinopathy, it is reasonable to advocate CGM use, at least until glucose levels stabilize. Studies are also lacking in those with neuropathy, but individuals with autonomic neuropathy and significant glycemic variability, particularly in the presence of gastrointestinal symptoms, such as repeated vomiting, may benefit from CGM to help optimize glycemia. CGM can also be useful in those with autonomic neuropathy to protect the heart, particularly in the presence of associated hypoglycemic unawareness [60]. In those with advanced peripheral neuropathy, CGM can be useful in the presence of foot ulcers, particularly with associated infections that may reduce the risk of advanced limb complications.
In those with recent MI, CGM use can help to reduce HbA1c safely without excessive hypoglycemia exposure and it is also cost-effective, although hard outcome studies are lacking. CGM may also be helpful for those with strokes, but similarly to patients with MI, outcome studies are lacking. Figure 2 summarizes the rationale and evidence for CGM use in individuals with T2D with clinically significant diabetes complications, while Table 1 highlights gaps in knowledge and further studies required.
Continuous glucose monitoring (CGM) in individuals with type 2 diabetes (T2D) with vascular complications. Rationale and evidence for CGM use are demonstrated in individuals with micro- and/or macro-vascular complications. GV glycemic variability, HA hypoglycemia unawareness, MI myocardial infarction
Use of CGM in T2D with Associated Conditions
There are a number of groups with T2D and associated clinical conditions and in whom use of CGM may be particularly helpful. These groups are briefly discussed below.
Surgical Patients
An association between perioperative hyperglycemia and poor clinical outcome has been repeatedly documented [61]. For routine operations, improving glycemia is advocated but this is not easily achievable. Use of CGM has the potential to quickly and safely improve glycemia both before and after surgery and studies in this area are urgently needed.
Patients with Cancer
The outcome of individuals with diabetes and cancer is inferior to those with cancer without diabetes [62]. Mortality in the diabetes group remains higher together with increased rate of unplanned hospital admissions and lower percentage of patients completing chemotherapy. The exact mechanisms for this inferior outcome are not entirely clear but hyperglycemia has been implicated [63]. Moreover, cancer therapies can result in the development of diabetes with a number of cancer agents inducing abnormal glucose metabolism through increased insulin resistance and/or impaired insulin secretion [63]. Identification of metabolic abnormalities early in these patients can help to optimize glycemic management, which in turn may have a positive impact on outcome. There are no published studies on CGM use in patients with cancer and diabetes, which represents a knowledge gap but a number of trials are now ongoing in various cancers that should provide important data (NCT04938869; NCT06011473; NCT04942756). One of these studies will investigate not only the role of CGM in improving glycemia but will also clarify whether such a glucose monitoring strategy improves outcomes including successful completion of chemotherapy and unplanned hospital admissions, while also analyzing quality-of-life measures and mortality.
Patients with Psychiatric Disorders
T2D is more common in individuals with significant psychiatric conditions, related to increased insulin resistance secondary to various therapies coupled with reduced exercise [64]. Despite the potential benefits, CGM in this group is not routinely used and there are concerns that it may increase anxiety, negatively impacting the psychiatric condition. Studies in this group of patients are warranted and a recent pilot work has shown promising results with these individuals tolerating blinded CGM while showing an interest in knowing their glucose data [65]. These encouraging results pave the way for a larger study using unblinded sensors in individuals with diabetes and advanced psychiatric conditions.
Patients During Hospital Admissions
CGM for hospitalized individuals has a great potential for both patients and the clinical workforce. Keeping glucose levels to target in individuals with T2D during hospital admission may reduce length of stay and limited data suggest that CGM use in these patients may be beneficial [66]. However, studies to date have been relatively small, and larger more carefully designed multicenter randomized controlled trials are needed to fully understand the role of CGM in T2D during hospital admission. Some may raise concerns over the increased workload of the clinical teams with CGM use. In practice, however, this technology is likely to make the clinical management of glycemia more effective with the potential to reduce the clinical workload by limiting reviews to individuals who show sustained and highly abnormal glucose patterns. Studies in this area are required to fully understand the role of CGM during hospital admissions, including assessment of cost-effectiveness. If CGM proves to improve outcomes and/or reduce length of hospital stay and is subsequently implemented for in-patient care, protocols will need to be developed that take into account local resources and clinical practice for the medical teams to adequately respond to CGM-detected glycemic abnormalities.
Another concern with CGM use in acutely unwell patients is accuracy, as these patients can have significant derangement in various metabolic parameters, with unknown effects on CGM readings. However, work in intensive care units has shown that CGM maintains accuracy in severely unwell patients [67], giving some reassurance but further studies are needed to ensure accuracy is maintained in all those who are acutely unwell.
People with Disabilities
Specific CGM studies in individuals with physical or mental disability are lacking, despite the potential enhanced benefits in these groups. For example, in individuals with advanced visual impairment, the use of CGM with alarm would help to avoid extremes of glycemia, and which can be particularly difficult to manage using SMBG. In those with a physical disability that can make SMBG difficult, or even impossible, such as Parkinson’s disease, rheumatoid arthritis, or previous stroke, CGM can provide a simple means for checking glucose levels and keeping the individual safe. CGM may also be helpful in the presence of mental disabilities, particularly in individuals who are unable to handle SMBG or find finger pricking distressing. Moreover, CGM offers carers of individuals with disabilities the opportunity of remote monitoring, including nocturnal glucose checks without interrupting the sleep of the individual with diabetes, which alleviates anxiety and ensures a better quality of life for both the individual with the disability and the carer.
While studies in such a group of individuals are needed to assess the effectiveness of CGM, it can be argued that some of these individuals have complex needs and studies may fail to reflect this at an individual level. Therefore, it is perhaps better to adopt a pragmatic approach and give CGM a try in these individuals followed by a long-term decision on CGM use based on the feedback from the individual and/or improvement in glycemic markers. Importantly, such decisions should be made jointly between the person with the disability and/or carer, and the HCP.
CGM in Pregnancy and Gestational Diabetes
This is a quickly expanding area with CGM use in T1D during pregnancy showing a positive impact on neonatal outcome [68]. Given that pregnancy is not a clinical condition per se but a temporary physiological process, it is beyond the scope of the current work to discuss T2D or gestational diabetes in pregnancy with extensive high-quality reviews in this area found elsewhere [69,70,71].
CGM in the Geriatric Population
While older age is a physiological process, many older individuals will have multimorbidity, which may complicate diabetes management. As the prevalence of diabetes continues to grow, clinicians will be challenged to provide care to an increasing number of older adults. Growing evidence suggests that the use of CGM has the potential to improve glycemic control, reduce hypoglycemia, decrease the burden of diabetes, and improve quality of life in the older T2D populations [72, 73].
Practical Considerations for Patients with T2D and Associated Conditions
In T2D scheduled for routine surgery, use of CGM may help to optimize perioperative glycemia, which in turn may improve outcomes. Therefore studies in this area are warranted. In individuals with cancer, the use of CGM can help glycemic management, which may, in turn, impact the outcome and quality of life, but evidence in this cohort is lacking. Individuals with psychiatric disorders may find CGM helpful for managing their diabetes. However, studies are needed to ensure that having detailed glucose data does not increase anxiety or worsen their psychiatric condition. CGM use for in patient has the potential to improve outcomes and may even result in early discharge but more studies in this area are required. There is a lack of studies of CGM use in people with physical or mental disabilities, although it is likely that CGM proves to be useful in these individuals. Conducting studies in such groups may be challenging due to their complex needs. Therefore, it may be best to make individual assessments and trial the use of CGM. Based on the results, a clinical decision can then be made regarding the helpfulness of this technology. Finally, in the older diabetes population, use of CGM may help to decrease the burden of diabetes and improve quality of life, particularly in the presence of multimorbidity. Figure 3 summarizes the rationale and evidence for CGM use in individuals with T2D and associated co-morbidities, while Table 1 highlights gaps in knowledge and further studies required.
Potential Disadvantages of CGM
While CGM has undoubted benefits in some groups of individuals with T2D, more evidence is required in others. Also, there are drawbacks to CGM use that should be highlighted. First, there are cost implications with most health systems unable to fund widespread use of CGM for the entire T2D population. Therefore, a nuanced approach is needed by initially targeting high-risk T2D groups and those who would benefit the most, while also considering intermittent use if there is enough evidence supporting this approach. Second, for CGM to be effective, both HCP and patients require appropriate education, which is not always available, as it is resource intensive. The importance of education has been recently highlighted by demonstrating superior glycemia in MDI-treated individuals with T2D when CGM was combined with education on the interpretation of glucose patterns [74]. Third, it has been argued that CGM increases the length of the clinical consultation, which adds to provider burden. However, the counter argument is that CGM makes the consultation more meaningful, helping to reduce diabetes complications and thus shortening diabetes consultations in the long run. Fourth, CGM positively affects quality-of-life measures but increased anxiety and feeling overwhelmed by glucose data have also been reported in younger individuals with T1D [75]. There is no convincing evidence for increased CGM-related anxiety in older individuals with T2D, although this may be due to the lack of specific studies and more work in this area is required. Fifth, there are concerns related to accuracy, particularly at the hypoglycemic range, and these concerns are compounded by the lack of education on the time lag between capillary and interstitial glucose levels. There is little doubt that accuracy of modern CGM devices has greatly improved, and continues to improve, although it is crucial that patients have access to capillary glucose measurement that should be undertaken if there is a disconnect between CGM readings and symptoms.
Conclusions
In the past decade, CGM use has revolutionized the management of diabetes, although the focus has mainly been on T1D. Individuals with T2D have not received the same access to such a technology given this is a much larger group with far greater clinical heterogeneity. Nevertheless, CGM use has been gradually expanding to insulin-treated individuals with T2D, given this is a high-risk group. However, this subgroup represents a minority of patients with T2D and expanding to other subgroups may help to limit various diabetes complications. A clear obstacle to this is the cost implications, as advocating CGM to all patients with T2D is a major financial commitment and it can be argued it is only necessary in these individuals at certain time points in the course of diabetes. Therefore, future work is needed to understand which subgroup of patients with T2D benefits the most while also undertaking appropriate cost-effectiveness analysis to target those with the most urgent needs. So far, the cost-effectiveness of CGM has been shown in T2D on intensive insulin therapy and in those who have had a cardiac event, provided they are on treatment with insulin and/or a sulphonylurea. Similar studies and cost-effectiveness analyses are required to roll out CGM to other groups on patients with T2D. It should be noted that CGM may turn out to be a cost-saving measure if it reduces the risk of diabetes complications, which remain the major, even the main, contributor to the high cost associated with this chronic condition. It is hoped that widespread use of CGM results in cost reduction of these devices, favorably impacting cost-effectiveness.
References
UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131):837–53.
Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353(25):2643–53.
Nathan DM. The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: overview. Diabetes Care. 2014;37(1):9–16.
Gallagher EJ, Le Roith D, Bloomgarden Z. Review of hemoglobin A(1c) in the management of diabetes. J Diabetes. 2009;1(1):9–17.
Khunti K, Seidu S. Therapeutic inertia and the legacy of dysglycemia on the microvascular and macrovascular complications of diabetes. Diabetes Care. 2019;42(3):349–51.
Amiel SA, Aschner P, Childs B, Cryer PE, de Galan BE, Frier BM, Gonder-Frederick L, Heller SR, Jones T, Khunti K, Leiter LA, Luo Y, McCrimmon RJ, Pedersen-Bjergaard U, Seaquist ER, Zoungas S. Hypoglycaemia, cardiovascular disease, and mortality in diabetes: epidemiology, pathogenesis, and management. Lancet Diabetes Endocrinol. 2019;7(5):385–96.
Marx N, Federici M, Schutt K, Muller-Wieland D, Ajjan RA, Antunes MJ, et al. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J. 2023;44(39):4043–140.
Clar C, Barnard K, Cummins E, Royle P, Waugh N. Self-monitoring of blood glucose in type 2 diabetes: systematic review. Health Technol Assess. 2010;14(12):1–140.
Elgart JF, Gonzalez L, Prestes M, Rucci E, Gagliardino JJ. Frequency of self-monitoring blood glucose and attainment of HbA1c target values. Acta Diabetol. 2016;53(1):57–62.
Ajjan RA. How can we realize the clinical benefits of continuous glucose monitoring? Diabetes Technol Ther. 2017;19(S2):S27–36.
Beck RW, Riddlesworth T, Ruedy K, Ahmann A, Bergenstal R, Haller S, et al. Effect of continuous glucose monitoring on glycemic control in adults with type 1 diabetes using insulin injections: the DIAMOND randomized clinical trial. JAMA. 2017;317(4):371–8.
Lind M, Polonsky W, Hirsch IB, Heise T, Bolinder J, Dahlqvist S, et al. Continuous glucose monitoring vs conventional therapy for glycemic control in adults with type 1 diabetes treated with multiple daily insulin injections: the GOLD randomized clinical trial. JAMA. 2017;317(4):379–87.
Deshmukh H, Wilmot EG, Gregory R, Barnes D, Narendran P, Saunders S, et al. Effect of flash glucose monitoring on glycemic control, hypoglycemia, diabetes-related distress, and resource utilization in the association of British clinical diabetologists (ABCD) nationwide audit. Diabetes Care. 2020;43(9):2153–60.
Leelarathna L, Evans ML, Neupane S, Rayman G, Lumley S, Cranston I, et al. Intermittently scanned continuous glucose monitoring for type 1 diabetes. N Engl J Med. 2022;387(16):1477–87.
Jackson MA, Ahmann A, Shah VN. Type 2 diabetes and the use of real-time continuous glucose monitoring. Diabetes Technol Ther. 2021;23(S1):S27–34.
Ajjan RA, Battelino T, Xavier C, Del Prato S, Philips J-C, Meyer L, Seufert J, Seidu S. Continuous glucose monitoring in personspeople with type 2 diabetes who are not on non-intensive insulin therapy. Nat Rev Endocrinol. 2024;20(7):426–40.
Fonseca VA. Defining and characterizing the progression of type 2 diabetes. Diabetes Care. 2009;32(Suppl 2):S151–6.
Hallberg SJ, Gershuni VM, Hazbun TL, Athinarayanan SJ. Reversing type 2 diabetes: a narrative review of the evidence. Nutrients. 2019;11(4):766.
Haak T, Hanaire H, Ajjan R, Hermanns N, Riveline JP, Rayman G. Flash glucose-sensing technology as a replacement for blood glucose monitoring for the management of insulin-treated type 2 diabetes: a multicenter, open-label randomized controlled trial. Diabetes Ther. 2017;8(1):55–73.
Yaron M, Roitman E, Aharon-Hananel G, Landau Z, Ganz T, Yanuv I, et al. Effect of flash glucose monitoring technology on glycemic control and treatment satisfaction in patients with type 2 diabetes. Diabetes Care. 2019;42(7):1178–84.
Beck RW, Riddlesworth TD, Ruedy K, Ahmann A, Haller S, Kruger D, et al. Continuous glucose monitoring versus usual care in patients with type 2 diabetes receiving multiple daily insulin injections: a randomized trial. Ann Intern Med. 2017;167(6):365–74.
Martens T, Beck RW, Bailey R, Ruedy KJ, Calhoun P, Peters AL, et al. Effect of continuous glucose monitoring on glycemic control in patients with type 2 diabetes treated with basal insulin: a randomized clinical trial. JAMA. 2021;325(22):2262–72.
Oser TK, Cucuzzella M, Stasinopoulos M, Moncrief M, McCall A, Cox DJ. An innovative, paradigm-shifting lifestyle intervention to reduce glucose excursions with the use of continuous glucose monitoring to educate, motivate, and activate adults with newly diagnosed type 2 diabetes: pilot feasibility study. JMIR Diabetes. 2022;7(1): e34465.
Choe HJ, Rhee EJ, Won JC, Park KS, Lee WY, Cho YM. Effects of patient-driven lifestyle modification using intermittently scanned continuous glucose monitoring in patients with type 2 diabetes: results from the randomized open-label PDF study. Diabetes Care. 2022;45(10):2224–30.
Monnier L, Colette C, Dunseath GJ, Owens DR. The loss of postprandial glycemic control precedes stepwise deterioration of fasting with worsening diabetes. Diabetes Care. 2007;30(2):263–9.
Wada E, Onoue T, Kobayashi T, Handa T, Hayase A, Ito M, et al. Flash glucose monitoring helps achieve better glycemic control than conventional self-monitoring of blood glucose in non-insulin-treated type 2 diabetes: a randomized controlled trial. BMJ Open Diabetes Res Care. 2020;8(1): e001115.
Aronson R, Brown RE, Chu L, Bajaj HS, Khandwala H, Abitbol A, et al. IMpact of flash glucose Monitoring in pEople with type 2 Diabetes Inadequately controlled with non-insulin Antihyperglycaemic ThErapy (IMMEDIATE): a randomized controlled trial. Diabetes Obes Metab. 2023;25(4):1024–31.
Matyka K, Evans M, Lomas J, Cranston I, Macdonald I, Amiel SA. Altered hierarchy of protective responses against severe hypoglycemia in normal aging in healthy men. Diabetes Care. 1997;20(2):135–41.
Ahmad I, Zelnick LR, Batacchi Z, Robinson N, Dighe A, Manski-Nankervis JE, et al. Hypoglycemia in people with Type 2 diabetes and CKD. Clin J Am Soc Nephrol. 2019;14(6):844–53.
Elwen FR, Huskinson A, Clapham L, Bottomley MJ, Heller SR, James C, et al. An observational study of patient characteristics and mortality following hypoglycemia in the community. BMJ Open Diabetes Res Care. 2015;3(1): e000094.
Goto A, Arah OA, Goto M, Terauchi Y, Noda M. Severe hypoglycaemia and cardiovascular disease: systematic review and meta-analysis with bias analysis. BMJ. 2013;347: f4533.
Zinman B, Marso SP, Christiansen E, Calanna S, Rasmussen S, Buse JB, Investigators LPCobotLT. Hypoglycemia, cardiovascular outcomes, and death: the LEADER experience. Diabetes Care. 2018;41(8):1783–91.
Hidayat K, Fang QL, Shi BM, Qin LQ. Influence of glycemic control and hypoglycemia on the risk of fracture in patients with diabetes mellitus: a systematic review and meta-analysis of observational studies. Osteoporos Int. 2021;32(9):1693–704.
Matthews DR, Paldanius PM, Proot P, Chiang Y, Stumvoll M, Del Prato S, group Vs. Glycaemic durability of an early combination therapy with vildagliptin and metformin versus sequential metformin monotherapy in newly diagnosed type 2 diabetes (VERIFY): a 5-year, multicentre, randomised, double-blind trial. Lancet. 2019;394(10208):1519–29.
Selvin E, Wang D, Rooney MR, Echouffo-Tcheugui J, Fang M, Zeger S, et al. The associations of mean glucose and time in range from continuous glucose monitoring with HbA1c in adults with type 2 diabetes. Diabetes Technol Ther. 2023;25(1):86–90.
Roussel R, Riveline JP, Vicaut E, de Pouvourville G, Detournay B, Emery C, et al. Important drop in rate of acute diabetes complications in people with type 1 or type 2 diabetes after initiation of flash glucose monitoring in France: the RELIEF study. Diabetes Care. 2021;44(6):1368–76.
Riveline JP, Roussel R, Vicaut E, de Pouvourville G, Detournay B, Emery C, et al. Reduced rate of acute diabetes events with flash glucose monitoring is sustained for 2 years after initiation: extended outcomes from the RELIEF study. Diabetes Technol Ther. 2022;24(9):611–8.
Guerci B, Roussel R, Levrat-Guillen F, Detournay B, Vicaut E, De Pouvourville G, et al. Important decrease in hospitalizations for acute diabetes events following freestyle libre system initiation in people with type 2 diabetes on basal insulin therapy in France. Diabetes Technol Ther. 2023;25(1):20–30.
Little RR, Rohlfing CL, Tennill AL, Hanson SE, Connolly S, Higgins T, et al. Measurement of Hba(1C) in patients with chronic renal failure. Clin Chim Acta. 2013;418:73–6.
Riveline JP, Teynie J, Belmouaz S, Franc S, Dardari D, Bauwens M, et al. Glycaemic control in type 2 diabetic patients on chronic haemodialysis: use of a continuous glucose monitoring system. Nephrol Dial Transplant. 2009;24(9):2866–71.
Yusof Khan AHK, Zakaria NF, Zainal Abidin MA, Kamaruddin NA. Prevalence of glycemic variability and factors associated with the glycemic arrays among end-stage kidney disease patients on chronic hemodialysis. Medicine (Baltimore). 2021;100(30): e26729.
Li J, Zhang R, Wu Z, Guo J, Wang Z, Li S, et al. Blood glucose fluctuation in older adults with diabetes mellitus and end-stage renal disease on maintenance hemodialysis: an observational study. Diabetes Ther. 2022;13(7):1353–65.
Bomholt T, Kofod D, Norgaard K, Rossing P, Feldt-Rasmussen B, Hornum M. Can the use of continuous glucose monitoring improve glycemic control in patients with type 1 and 2 diabetes receiving dialysis? Nephron. 2023;147(2):91–6.
Williams ME, Steenkamp D, Wolpert H. Making sense of glucose sensors in end-stage kidney disease: a review. Front Clin Diabetes Healthc. 2022;3:1025328.
Mansour SE, Browning DJ, Wong K, Flynn HW Jr, Bhavsar AR. The evolving treatment of diabetic retinopathy. Clin Ophthalmol. 2020;14:653–78.
Gad H, Elgassim E, Mohammed I, Alhaddad AY, Aly H, Cabibihan JJ, et al. Cardiovascular autonomic neuropathy is associated with increased glycemic variability driven by hyperglycemia rather than hypoglycemia in patients with diabetes. Diabetes Res Clin Pract. 2023;200: 110670.
Bell DSH. Detecting and treating the protean manifestations of diabetic autonomic neuropathy. Diabetes Obes Metab. 2023;25(5):1162–73.
Sanz-Corbalan I, Lazaro-Martinez JL, Garcia-Morales E, Molines-Barroso R, Alvaro-Afonso F, Garcia-Alvarez Y. Advantages of early diagnosis of diabetic neuropathy in the prevention of diabetic foot ulcers. Diabetes Res Clin Pract. 2018;146:148–54.
Tian XF, Cui MX, Yang SW, Zhou YJ, Hu DY. Cell death, dysglycemia and myocardial infarction. Biomed Rep. 2013;1(3):341–6.
Stampouloglou PK, Anastasiou A, Bletsa E, Lygkoni S, Chouzouri F, Xenou M, et al. Diabetes mellitus in acute coronary syndrome. Life (Basel). 2023;13(11):2226.
Malmberg K. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group. BMJ. 1997;314(7093):1512–5.
Mellbin LG, Malmberg K, Norhammar A, Wedel H, Ryden L, Investigators D. The impact of glucose lowering treatment on long-term prognosis in patients with type 2 diabetes and myocardial infarction: a report from the DIGAMI 2 trial. Eur Heart J. 2008;29(2):166–76.
Ajjan RA, Heller SR, Everett CC, Vargas-Palacios A, Higham R, Sharples L, et al. Multicenter randomized trial of intermittently scanned continuous glucose monitoring versus self-monitoring of blood glucose in individuals with type 2 diabetes and recent-onset acute myocardial infarction: results of the LIBERATES trial. Diabetes Care. 2023;46(2):441–9.
Chamorro A, Brown S, Amaro S, Hill MD, Muir KW, Dippel DWJ, et al. Glucose modifies the effect of endovascular thrombectomy in patients with acute stroke. Stroke. 2019;50(3):690–6.
Borggrefe J, Gluck B, Maus V, Onur O, Abdullayev N, Barnikol U, et al. Clinical outcome after mechanical thrombectomy in patients with diabetes with major ischemic stroke of the anterior circulation. World Neurosurg. 2018;120:e212–20.
Litke R, Moulin S, Cordonnier C, Fontaine P, Leys D. Influence of glycaemic control on the outcomes of patients treated by intravenous thrombolysis for cerebral ischaemia. J Neurol. 2015;262(11):2504–12.
Kersten C, Zandbergen AAM, Fokkert MJ, Slingerland RJ, den Hertog HM. Continuous glucose monitoring in acute ischemic stroke patients treated with endovascular therapy: a pilot study to assess feasibility and accuracy. PLoS One. 2023;18(2): e0280153.
Yapanis M, James S, Craig ME, O’Neal D, Ekinci EI. Complications of diabetes and metrics of glycemic management derived from continuous glucose monitoring. J Clin Endocrinol Metab. 2022;107(6):e2221–36.
Lin YK, Fisher SJ, Pop-Busui R. Hypoglycemia unawareness and autonomic dysfunction in diabetes: lessons learned and roles of diabetes technologies. J Diabetes Investig. 2020;11(6):1388–402.
Thompson BM, Stearns JD, Apsey HA, Schlinkert RT, Cook CB. Perioperative management of patients with diabetes and hyperglycemia undergoing elective surgery. Curr Diab Rep. 2016;16(1):2.
Birch RJ, Downing A, Finan PJ, Howell S, Ajjan RA, Morris EJA. Improving outcome prediction in individuals with colorectal cancer and diabetes by accurate assessment of vascular complications: Implications for clinical practice. Eur J Surg Oncol. 2021;47(5):999–1004.
Joharatnam-Hogan N, Morganstein DL. Diabetes and cancer: optimising glycaemic control. J Hum Nutr Diet. 2023;36(2):504–13.
Reilly S, Olier I, Planner C, Doran T, Reeves D, Ashcroft DM, et al. Inequalities in physical comorbidity: a longitudinal comparative cohort study of people with severe mental illness in the UK. BMJ Open. 2015;5(12): e009010.
Brown JVECP, Siddiqi N, Ajjan RA. Acceptability and feasibility of CGM for people with severe mental illness: a mixed-methods study. Diabetologia. 2023;66:S62.
Zelada H, Perez-Guzman MC, Chernavvsky DR, Galindo RJ. Continuous glucose monitoring for inpatient diabetes management: an update on current evidence and practice. Endocr Connect. 2023;12(10):e230180.
Finn E, Schlichting L, Grau L, Douglas IS, Pereira RI. Real-world accuracy of CGM in inpatient critical and noncritical care settings at a safety-net hospital. Diabetes Care. 2023;46(10):1825–30.
Feig DS, Donovan LE, Corcoy R, Murphy KE, Amiel SA, Hunt KF, et al. Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial. Lancet. 2017;390(10110):2347–59.
Benhalima K, Beunen K, Siegelaar SE, Painter R, Murphy HR, Feig DS, et al. Management of type 1 diabetes in pregnancy: update on lifestyle, pharmacological treatment, and novel technologies for achieving glycaemic targets. Lancet Diabetes Endocrinol. 2023;11(7):490–508.
Yamamoto JM, Murphy HR. Treating to target glycaemia in type 2 diabetes pregnancy. Curr Diabetes Rev. 2023;19(2): e010222200742.
Majewska A, Stanirowski PJ, Wielgos M, Bomba-Opon D. Efficacy of continuous glucose monitoring on glycaemic control in pregnant women with gestational diabetes mellitus—a systematic review. J Clin Med. 2022;11(10):2932.
Munshi MN. Continuous glucose monitoring use in older adults for optimal diabetes management. Diabetes Technol Ther. 2023;25(S3):S56–64.
Guerci B, Levrat-Guillen F, Vicaut E, De Pouvourville G, Detournay B, Emery C, Riveline JP. Reduced acute diabetes events after FreeStyle libre system initiation in people 65 years or older with type 2 diabetes on intensive insulin therapy in France. Diabetes Technol Ther. 2023;25(6):384–94.
Kim JY, Jin SM, Sim KH, Kim BY, Cho JH, Moon JS, et al. Continuous glucose monitoring with structured education in adults with type 2 diabetes managed by multiple daily insulin injections: a multicentre randomised controlled trial. Diabetologia. 2024;67(7):1223–34.
Patton SR, Clements MA. Psychological reactions associated with continuous glucose monitoring in youth. J Diabetes Sci Technol. 2016;10(3):656–61.
Funding
No funding or sponsorship was received for this study or publication of this article.
Author information
Authors and Affiliations
Contributions
Ramzi A. Ajjan designed the manuscript and contributed to all sections. Samuel Seidu and Jean Pierre Riveline contributed to specific sections. All three authors critically reviewed all sections and approved the manuscript.
Corresponding author
Ethics declarations
Conflict of Interest
Ramzi A. Ajjan: received honoraria for presentations and/or consultancy and/or research funding from Abbott Diabetes Care, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Meyers Squibb, Eli Lilly, GlaxoSmithKline, LifeScan, Menarini Pharmaceuticals, Merck-Sharp & Dohme, NovoNordisk, Roche, Sanofi and Takeda. Samuel Seidu: speaker honoraria, advisory board or educational grants: AstraZeneca, Boehringer Ingelheim, Janssen, Eli Lilly, MSD, Abbott, NovoNordisk, SB Communications, OmniaMed, Roche, Napp, NB Medical, Amgen, Sanofi. Jean Pierre Riveline: is an advisory panel member for Sanofi, MSD, Eli Lilly, Novo Nordisk, AstraZeneca, Abbott, Dexcom, Alphadiab, Air Liquide Healthcare and Medtronic and has received research funding from Abbott, Air Liquide Healthcare, Sanofi, and NovoNordisk.
Ethical Approval
This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
About this article
Cite this article
Ajjan, R.A., Seidu, S. & Riveline, J.P. Perspective of Continuous Glucose Monitoring-Based Interventions at the Various Stages of Type 2 Diabetes. Diabetes Ther (2024). https://doi.org/10.1007/s13300-024-01607-5
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s13300-024-01607-5