An updated algorithm for an effective choice of continuous glucose monitoring for people with insulin-treated diabetes

Figure 1. In people with type 1 diabetes with disabling hypoglycemia, or previous episodes of diabetic ketoacidosis (DKA), we suggest the rtCGM to customize alerts and alarms in order to predict impending hypoglycemia, acting quickly and avoid a potentially serious event. Systems with high accuracy in the low glucose range are recommended (Table 3). In the case of suboptimal glucose control, isCGM and rtCGM can both be suggested, depending on individual skills, patient preferences, smart devices availability, and costs.

CGM represents a fundamental therapeutic tool in type 1 diabetes since it allows to address the potential issues related to the "timing" of insulin administered at meals, the insulin-carbohydrate ratio (and more generally, the influence of other nutrients including proteins and fats) and the management of night period. In RCTs of adults with type 1 diabetes, both isCGM and rtCGM are effective in increasing the TIR and reducing the time spent in hypoglycemia (time below range, TBR) [7, 8, 11‐13]. Clinical benefits in terms of improved glucose control have been reported for youth and middle aged adults with poor diabetes control (HbA_1c ranging between 7.5%–11.0%) using rtCGM, and middle aged adults with HbA_1c closer to optimal range (6.8–8.7%) using isCGM (Table 2). Specifically, rtCGM with predictive alerts and alarms was associated with a reduction of a number of hypoglycemic events [14], including severe hypoglycemia [15, 16], decrease in TBR [15‐19], and an improvement in hypoglycemia awareness [15, 16, 20] in middle aged adults with type 1 diabetes prone to hypoglycemia or impaired awareness of hypoglycemia, and HbA_1c ranging between 7.5% and 8.2% (Table 2). Since hypoglycemia is the limiting factor of diabetes therapy and a major concerns for people with diabetes and their families, reducing both level 1 and level 2 hypoglycemia is critical to improve glucose daily oscillations, quality of life and diabetes distress and prevent serious hypoglycemic episodes occurring with loss of consciousness or seizures, respectively. Moreover, clinicians should be aware of the accuracy of the used device, in order to choice the systems with high accuracy in presence of persistent of prolonged hypoglycemia (Table 3).

The isCGM should be proposed in each patient at the onset of diabetes when insulin therapy is required (Fig. 2). Its use should be also considered in people with a recent diagnosis of diabetes presenting prevalent hyperglycemia or in people with autoimmune diabetes in the stage of “honeymoon” with reduced insulin requirements. In the presence of frequent and severe hypoglycemia (with or without recognized precipitating cause) and poor glucose control despite intensive insulin therapy, rtCGM may be used due to the possibility of customizable alerts/alarms that allow patients to recognize in advance the effect of actions/factors that influence glucose variability. In people who are unwilling or unable to engage in the routine use of CGM, the occasional use of isCGM may be suggested to evaluate glucose trends and to guide the related therapeutic choices.

Preventing diabetic complications and optimizing the quality of life are both goals of diabetes therapy. A person-centered approach, tailored on both individual preferences and needs, is essential for effective diabetes management [21]. Therefore, the achievement of glucose control should be pursued from the early stages to preserve PwD from long-term disabling complications [21, 22]. Expanding the use of CGM to all people at diabetes onset needing insulin therapy may support effective intensification of treatments valuable to reduce glucose exposure and glucose variability and lower the risk of complications and hospital admissions, which are associated with high economic burden. Of note, these goals may be achieved while minimizing the risk of hypoglycemia and improving quality of life for people with diabetes. Moreover, the analysis of glucose pattern may be used as an educational tool to demonstrate the relationship between an individual’s glucose levels, his/her medication, and other therapeutic interventions. There is evidence from observational studies that the early use (within one year from the diagnosis) of both isCGM [23] and rtCGM [24‐26] results in long-term improvement in HbA_1c and the reduction in diabetes-related emergency-department admissions in people with type 1 diabetes. Moreover, the use of CGM at the onset of diabetes allows patients to be aware of the glycemic trends and their changes following insulin therapy. On the other hand, CGM may help physicians to monitor glycemic control and hence optimize structured therapeutic education remotely. The use of an isCGM as the first choice at diabetes onset may be preferred, as it provides a less expensive device with automatic transmission of data, does not need calibrations, and is approved for insulin dosing without SMBG. Only when symptoms of hypoglycemia do not match the glucose level detected, or glucose levels are rapidly changing, SMBG has to be considered. Moreover, isCGM with optional alarms for high and low blood glucose may be useful in patients in good metabolic control at low risk of hypoglycemia who have physical, psychological, or occupational barriers to the regular use of capillary glucose monitoring. A rtCGM should be reserved to people with a recent diabetes diagnosis and poor glucose control (i.e. high glucose variability) or disabling hypoglycemia: this should be based on the possibility to set alarms for hypoglycemia, hyperglycemia and rapid variations in glucose, increasing further the effectiveness of clinical management.

Figure 3. In patients with type 2 diabetes treated with insulin therapy in whom hypoglycemia predominates, a rtCGM with predictive alerts and alarms should be used. In type 2 PwD with suboptimal glucose control and low risk for hypoglycemia who require more data than those offered by SMBG, both isCGM and rtCGM can be suggested, depending on the individual’s circumstances, preferences, and needs.

Studies evaluating the effects of CGM in people with type 2 diabetes are limited, especially those including patients not on intensive insulin therapy [9]. There is evidence from RCTs that rtCGM reduces HbA_1c and increases TIR in people with type 2 diabetes treated with multiple daily injections [27] or basal insulin [9], and is more effective than SMBG in minimizing hypoglycemia for people using therapies at high hypoglycemic risk [28]. Moreover, a recent large retrospective cohort study including 41753 participants with insulin-treated diabetes, of whom 36 080 with type 2 diabetes, showed that among adults who started rtCGM, those with type 2 diabetes had greater improvements in HbA_1c than patients with type 1 diabetes associated with reductions in emergency department visits and hospitalizations for hypoglycemia [29]. Of note, recent practice guidelines suggest the use of rtCGM for people with type 2 diabetes who take insulin and are at risk for hypoglycemia [30]. Furthermore, the intermittent use of rtCGM in people with type 2 diabetes on oral anti-diabetic drugs, with or without basal insulin, is emerging as an effective strategy in lowering HbA_1c in the short-term [31, 32].

In a recent meta-analysis of RCTs, the use of isCGM was shown to significantly reduce HbA_1c levels of −0.74% in participants with T2D, with a lower risk of hypoglycemia compared with SMBG, and a greater effect in participants aged ≤ 65 years [33]. A significant improvement in HbA_1c associated with isCGM has also been found in an observational study of people with type 2 diabetes on basal-bolus therapy [34]. Evidence relative to the efficacy of isCGM in improving glycemic outcomes, including a greater TIR, a lower TBR, and a higher reduction in HbA_1c levels, are also emerging among non-insulin-treated people with type 2 diabetes [35]. Finally, the use of isCGM should be a valuable therapeutic opportunity in people with type 2 diabetes and fair glucose control [36].

Figure 4. In the presence of pre-gestational diabetes (both type 1 and type 2), or gestational diabetes on intensive insulin therapy and suboptimal glucose control, the preferential use of rtCGM or alternatively an isCGM should be considered in addition to SMBG in order to frequently monitor blood glucose levels and achieve glucose targets throughout pregnancy. If there is a risk of maternal hypoglycemia, a rtCGM should be preferred.

An increasing corpus of evidence demonstrates that CGM (mainly rtCGM) can improve maternal pre-natal glucose levels and neonatal outcomes in women with pre-existing diabetes or gestational diabetes [37, 38]. The critical issues traditionally associated with insulin therapy in the management of diabetes become more evident during pregnancy, based on the reduced insulin sensitivity and tighter fasting and postprandial blood glucose targets to be achieved for the prevention of maternal and neonatal complications. In addition, the International Consensus on TIR endorses ambitious glucose targets for pregnant women with pre-existing type 1 diabetes [TIR 63–140 mg/dl (> 70%), TAR > 140 mg/dl (< 25%), TBR < 63 mg/dl (< 4%), TBR < 54 mg/dl (< 1%)] or pre-existing type 2 diabetes and gestational diabetes [4]. Therefore, the use of rtCGM over isCGM should be preferred because of the accuracy of the data, the possibility of enable high and low glucose alerts and predictive alarms for hypoglycemia, allowing an intense pattern of care while minimizing the risk of maternal hypoglycemia.

Figure 5 Both rtCGM and isCGM should be suggested in PwD performing sporting activities, based on individual preferences and personal experiences. In case of disabling hypoglycemia in PwD performing sporting activities a rtCGM should be preferred over isCGM.

Physical activity and exercise are associated with multiple health benefits for people with diabetes [39]. CGM is emerging as an effective tool to preserve glucose homeostasis during and after exercise in PwD, thanks to the opportunity to prevent hypoglycemic events and nocturnal hypoglycemia following physical activity [40, 41]. Both rtCGM and isCGM can be effective tools to help indicate when carbohydrate intake should be started to prevent or treat hypoglycemia during exercise, as emerged in studies involving adolescents and adults with type 1 diabetes [42, 43]. Moreover, the use of rtCGM allows setting alarms to minimize the risk of hypoglycemic episodes at the onset of exercise in type 1 diabetes [40].

Figure 6 In frail people with insulin-treated diabetes able to use the devices (either by themselves or with a caregiver) and recurrent hypoglycemic episodes without hypoglycemia awareness, a rtCGM should be suggested in order to reduce the risk of hypoglycemic events. If the awareness of hypoglycemia is preserved, an isCGM may be considered. In the case of suboptimal glycemic control, the choice of a rtCGM or isCGM should be based on the wearability and portability of the devices and individual preferences.

Older adults with diabetes mellitus and long disease duration are at greater risk of prolonged and often unnoticed hypoglycemia, than younger adults. In order to minimize the risk of hypoglycemia, the International Consensus on TIR recommends less stringent glycemic targets in this subgroup [TIR > 50%, TBR (< 70 mg/dl) < 1%, TAR level 1 (> 180 mg/dl) < 50%, TAR level 2 (> 250 mg/dl) < 1] [4]. Evidence from Wireless Innovation in Seniors with Diabetes Mellitus (WISDM) and observational data from DCCT/EDIC study report the effectiveness of CGM in reducing the risk of hypoglycemia up-to one year [15, 18], hyperglycemic excursions and in reaching desired HbA_1c levels [44] in older people with type 1 diabetes. The benefits associated with CGM, in terms of improved HbA_1c and reduced glycemic variability, are also emerging in studies involving older people with type 2 diabetes using insulin [28, 45]. Particularly, the use of a rtCGM with alerts or predictive alarms by the user and/or the caregiver represents one of the most useful therapeutic tools to avoid hypoglycemia or mitigate its severity in this high-risk population of PwD. Emerging evidence reports the effectiveness of CGM in lowering mean glucose levels during and after hemodialysis in people with type 2 diabetes and stage 3–5 chronic kidney disease (CKD) [46, 47]. This is relevant, as CGM can reveal the daily glucose trends for PwD and CKD on hemodialysis and help them manage daily diet and physical activity.