Approved Indications of Use

CGM systems are approved for use in people with type 1 and type 2 diabetes aged 2 years old and above, with brand-specific age approval.

CGM use has been evaluated also in pregnant women with diabetes and has been found to be both safe and efficacious in improving the health of offspring through better management of maternal glucose levels [22,23,24,25]. However, only few CGM systems are officially licensed by the regulatory bodies for use in pregnant women.

Adjunctive CGM requires the user verify their glucose levels or trends with a BG meter prior to any treatment decision-making. For a few years, some devices are claimed for non-adjunctive use owing to their improved accuracy. Nevertheless, confirmatory finger-pricking is always required when sensor readings do not match the patient’s symptoms or expectations, and in case of assumption of medications that interfere with the sensor readings (e.g. paracetamol, high dose of ascorbic acid) [26].

Complying with the indications contained in the technical data sheet is crucial for safe and successful use of devices in clinical practice. For people with physical, psychological, or occupational barriers to regular use of SMBG, CGM with non-adjunctive use (i.e. not requiring SMBG for confirmation) should be considered as first choice.

Alerts

CGM systems are equipped with a variety of alerts notifying the users of critical changes in glucose levels, with the aim to foster timely intervention and limit severe hypo- and hyperglycaemia. CGM alerts include high/low alerts, which notify the users when glucose levels cross specified thresholds, predictive alerts, which anticipate changes in glucose levels before they occur, and rate of change alerts, which indicate rapid rise or fall in glucose levels [14].

Optional Alerts

Most of CGM systems have visual, audible and/or vibratory alerts for glucose that cannot be disabled; however few systems allow the users the choice to turn off all the alerts according to their individual needs and preference.

Although glucose alerts are important for mitigating the occurrence and severity of acute events by warning the users of actual and impending hypoglycaemia and hyperglycaemia, they can sometimes become a source of nuisance [27]. Indeed, CGM users may feel overwhelmed and fatigued with too many alerts (in particular, false or useless ones) interrupting their usual activities, and, over time, become less prone to react appropriately to true alerts [28]. Moreover, nocturnal alarm fatigue has been identified as a major cause of disrupted sleep and CGM discontinuation [29]. Also, “alarm embarrassment” has been described when alerts occur in situations of social exposure, e.g. in the middle of an important meeting. Adolescents are particularly concerned about this issue and may refuse a system with alerts that cannot be silenced as a result of worry about the alerts going off in school and causing them to be the focus of attention [30].

CGM systems with optional alerts provide the flexibility to disable alerts temporarily to address alarm fatigue and/or embarrassment and accommodate professional or privacy considerations [30]. Therefore, they can be considered for PwD who find CGM alerts troublesome, and particularly for CGM-naïve PwD who are reluctant to even try CGM because of concerns about how the alerts will affect the quality of their lives. Of note, in the latter scenario expert opinion papers suggest keeping any alerts disabled for an initial period of 1–2 weeks of sensor use, unless the user experiences frequent hypoglycaemia or has hypoglycaemia unawareness; in such cases, setting a low glucose alert may be appropriate from the outset [31]. Such a stepwise approach may allow the user to become comfortable with other aspects of CGM and avoid a potentially overwhelming multitude of high and low alerts.

Predictive Alerts

While all CGM systems allow high/low alerts to be sent to the reader or connected device, only few have also predictive alerts. Specifically, few have a non-modifiable predictive alert (the so-called urgent low soon [ULS] alert) that warns the users when their glucose readings are predicted to reach 3 mmol/L (55 mg/dL) within 20 min, while other systems have alerts for either hypo- and hyperglycaemia prediction that can be customized both in their threshold and their time of prediction, in this way aligning the device functionality with individual treatment plans and lifestyle preferences. Scientific evidence supports the benefits of predictive alerts. Real-world analyses demonstrate that enabling predictive alerts in CGM systems significantly reduces the occurrence of both high and low glucose excursions in individuals with diabetes either on multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) therapy [32]. Furthermore, research in adolescents with type 1 diabetes underscores the superiority of predictive alerts in reducing time spent in hypoglycaemia and risks associated with glycaemic variability as compared with threshold alerts [33]. More recently, activation of the ULS alert has been linked to significant reductions in exposure to hypoglycaemia below 2.8 mmol/L (50 mg/dL) in the 24 h after exercise compared with a threshold alert [34, 35].

For individuals experiencing problematic hypoglycaemia, i.e. characterised by frequent or severe episodes, nocturnal occurrences, or a lack of awareness of hypoglycaemic states, CGM systems with predictive alerts are crucial, as they can pre-emptively notify the users, allowing them to take appropriate action to prevent a hypoglycaemic event and any subsequent hyperglycaemic rebound. Moreover, predictive alerts may be considered for PwD regularly engaged in physical activity who need an enhanced layer of protection against hypoglycaemia. By contrast, for those with a lower risk of hypoglycaemia, such as individuals with newly diagnosed type 2 diabetes or those on less intensive therapies, CGM with threshold alerts may be adequate.

On-Body Vibrations

A unique feature offered by a specific CGM system with fully implantable sensor is the provision of vibration alerts directly on the body through a “smart” transmitter. These tactile notifications are activated when specific glucose thresholds are reached or anticipated, providing a subtle yet effective alerting mechanism that is beneficial in situations where audible alerts may go unnoticed or are undesirable, or when the users do not have visual access to their device’s display [14].

Therefore, these alerts may be fitting for PwD who are not able to check their device frequently, such as during sleep, while driving, or in loud environments.

Interoperability and Integration with Other Devices

Some CGM systems are designed to work in connection with specific insulin pumps and connected insulin pens to provide additional functionalities and data analysis [36]. Of note, the FDA has coined the definition of iCGM to indicate CGM systems that “are designed to reliably and securely transmit glucose measurement data to digitally connected devices” for the purpose of glycaemic management [18]. On the other hand, device interoperability has been defined as “the ability of medical devices to communicate with each other, and/or work together as intended” and includes the concept of interchangeability of components in a system [37].

Connected pens can record and wirelessly transmit information on dose and time of insulin injections, with the most advanced systems also providing reminders, bolus calculation, and active insulin estimation [36]. It has been demonstrated that use of connected pens is associated with fewer missed bolus injections, increased time in range (TIR), decreased hypoglycaemia, increased satisfaction, and economic benefits [38,39,40,41]. Moreover, availability of integrated CGM and insulin data may help identify abnormal glucose events and/or recurrent glucose patterns and guide appropriate therapy changes, in this way overcoming therapeutic inertia [36]. A recent consensus of experts has identified the patient profiles that are supposed to benefit the most from using connected pens, including PwD who omit or delay mealtime insulin doses, those with inadequate glucose control, and individuals relying on caregivers for insulin administration [36].

Integration of CSII and CGM technology has allowed for development of sophisticated systems providing AID, including automated suspension of basal insulin delivery in response to a detected low glucose level (low glucose suspend, LGS) or a predicted low glucose level (predictive low glucose suspend, PLGS) and closed-loop regulation of insulin delivery to manage both high and low glucose levels [42].

Several randomised clinical trials and meta-analyses have shown the benefits of AID over non-integrated systems on HbA1c levels, TIR, and glycaemic variability, with similar or even improved psychosocial outcomes [43].

From a clinical practice standpoint, careful consideration of interoperability of CGM devices should be integral to the routine decision-making process, as it allows a stepwise approach to technology implementation in diabetes care (i.e. switching from a connected pen to an insulin pump communicating with the same CGM system).

PwD who are candidates for use of connected pens should be preferably oriented towards CGM devices that can interface with these pens [36]. On the other hand, for PwD who are already using an insulin pump and are happy with it, but also for individuals on MDI who are considering closed-loop therapy in the near future, choosing CGM devices that communicate with pumps is important for enabling AID [44].

However, possible barriers to the implementation of connected pens in a real-life context have been identified, including patient preference and motivation, insurance coverage, insulin compatibility, need for an advanced diabetes education, poor digital competence, owning a non-compatible smartphone, lack of training on digital tools for HCPs, obtaining and using data report [36, 45]. Also, PwD may not be interested in the integration of the CGM system with an insulin pump because of cost, alarm annoyance, perceptions of accuracy, body image issues, and perceived hassle [44].

In this scenario, the HCPs have the responsibility to keep themselves updated on the latest advancements, explain the expected benefits of integrated technologies, address any concern that PwD may have, and offer support for enhancing their technological skills. Ultimately, if a person is still not interested in integrated systems, a CGM device that is intended only for standalone use could be offered.

Approved Application Sites

Approved application sites for CGM systems may vary for adult and paediatric PwD to accommodate anatomical considerations. Indeed, in adult subjects the approved sites typically include the abdomen or the back of the upper arm, while for the paediatric population between 2 and 17 years of age the upper buttocks are also an approved site, acknowledging the differences in body composition and activity levels in younger individuals [14]. Importantly, the number of approved sites may vary with the different brands, ranging between one and more than one.

Having two or three alternative sites that are approved for sensor placement is essential for individuals who experience sensor accuracy issues, have localised lipodystrophy, or prefer a more concealed sensor placement for personal comfort or aesthetic reasons.

Available Visualization Devices

All the latest-generation systems allow real-time data visualization through a smartphone application; however, few also offer a dedicated handheld receiver (for certain systems referred to as the reader).

While the availability of a dedicated receiver meets the needs of those who do not have a compatible smartphone or choose not to rely on the smartphone as part of their diabetes management strategy, use of apps enables real-time remote monitoring from caregivers or HCPs [43].

Real-time sharing and following of CGM data in children and elderly or frail adults have allowed for better sleep and fewer episodes of severe hypoglycaemia, providing peace of mind and a sense of security for both PwD and their caregivers [43, 46, 47]. The advantages of real-time remote monitoring have been demonstrated also in other settings like hospitals, where PwD are often bedridden, and healthcare staff need to monitor multiple individuals simultaneously [48, 49]. Of note, a clinical trial evaluating the use of CGM combined with a glucose telemetry system, which wirelessly transmits CGM data to a centralised monitor, has recently demonstrated the potential to reduce hypoglycaemic events significantly in a non-critical care hospital setting [48]. This approach facilitates the management of glucose levels without placing additional burdens on bedside nurses, and PwD have well tolerated the use of these devices without significant complaints of discomfort or sleep interruption [50].

Moreover, use of apps can enable auditory access to key information including current glucose, trend arrows, and glucose alerts through text-to-speech solutions, in this way supporting diabetes management in visually impaired patients with diabetes. Of note, in a small cohort of legally blind patients with diabetes from the U.S., voice-activation resulted in improved TIR and HbA1c without increased hypoglycaemia [51].

For individuals who are not inclined toward the latest technology or who do not possess a latest-generation smartphone, a CGM system with a dedicated receiver is often preferred. Moreover, the option of a dedicated receiver can simplify the user experience for those who prefer to keep use of their medical and personal device separate. On the other hand, availability of the Share feature in CGM systems is especially valuable for parents of children with diabetes and caregivers of frail/older adults.

Removable Transmitter

The transmitter is a component that wirelessly communicates glucose data from the sensor to a separate reader or smartphone. There are various designs of transmitters across different CGM systems; however, one single system allows the transmitter to be removed as needed without sacrificing the sensor [52].

This removability is pivotal for individuals who need to temporarily remove external medical devices for professional or privacy reasons, are engaged in contact sports, or require frequent skin care to minimize the risk of allergic or hypersensitivity reactions to the adhesives used in CGM devices [52].

The removability of the transmitter also allows for safe completion of MRI imaging procedures, assuming specific conditions are met to ensure the patient’s safety and the integrity of the sensor.

Cost of Devices

While there is growing evidence that CGM may be cost-effective both in people with type 1 and type 2 diabetes, including those on basal insulin therapy, cost of devices is still a major barrier to widespread use of this technology [44, 53,54,55,56,57]. The cost of a CGM system can vary significantly depending on brand, features, and insurance coverage. Moreover, while health insurance plans generally cover the costs of CGM devices, each plan may have different benefits and requirements, so that pricing ultimately acts as a relevant driver of choice for many PwD. In the Italian scenario, the National Health System permits the reimbursement of devices in people with either type 1 and type 2 diabetes; however, eligibility criteria and budget vary from one region to the other, and competitive bidding processes may restrict access to specific products [58].

Anyway, amongst people with low socio-economic means, lower access to CGM has been reported irrespective of reimbursement issues [59]. Therefore, prescription and education pathways should be aimed at avoiding potential discriminations.