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Abstract

Background:

Continuous glucose monitoring (CGM)/flash glucose monitoring (FGM) use in diabetes management is increasing. Cutaneous complications associated with these devices were reported. We conducted a systematic review to provide an overview of cutaneous complications with CGM/FGM use.

Methods:

We identified observational studies and intervention trials that report on cutaneous complications with CGM/FGM use up to January 14, 2019. Studies were identified through Medline, Embase, and PubMed, or with hand searching of the previous publications. Screening was duplicated and data extracted to consider four main themes: incidence rate and severity, participant perspectives of cutaneous complications, potential solutions, and future directions in diabetic technology relevant to reducing cutaneous complications.

Results:

A total of 54 eligible studies were identified. The overall event rate of cutaneous complications reported from 19 trials was one event per eight weeks of sensor wear-time of which 1.5% were considered severe. The most common cutaneous complications were wear-related erythema, itching, and induration. Although skin irritations were the most common cause of CGM/FGM discontinuation, most users experienced less pain or discomfort with CGM/FGM than capillary blood glucose testing. Future technological advances may reduce, but not eliminate cutaneous complications.

Conclusion:

The incidence rate of reported cutaneous complications with CGM/FGM use from the available literature is low, with one event per eight weeks of sensor wear-time. Reported complication severity was also low, leading to low rates of CGM/FGM discontinuation. However, there appear to be discrepancies between reporting in trial and observational data. Greater constancy in reporting is necessary to understand the frequency of this issue.

Keywords

adverse events cutaneous complications glucose sensing technology

Introduction

Achieving healthy glycemic control is a critical goal for those with diabetes given the increased risk of both micro- and macrovascular complications.^1,2 Crucial to achieving this is frequent self-monitoring of glucose.^3,4 Given the limitations of traditional capillary glucose monitoring,⁵ interstitial glucose monitoring such as continuous glucose monitoring (CGM) and flash glucose monitoring (FGM) is growing in popularity.⁶ These devices typically involve the insertion of a sensor under the skin that requires additional external securing with an adhesive cutaneous patch for periods usually of 6 to 14 days. Results from CGM/FGM trials indicate reductions in hypoglycemia and improvements in glycated hemoglobin (HbA1c)^7-12 suggesting that their use in standard diabetes care is likely to increase, particularly as they are also a crucial component of automated insulin delivery technology. For the above reasons, newly published guidelines recommend CGM as standard care for children and adolescents with type 1 diabetes.¹³

Cutaneous complications arising from insulin pump technology, which use similar adhesives, have been previously reported¹⁴ and are now also emerging in the CGM/FGM literature.^15-19 These often involve degrees of allergic contact dermatitis from CGM/FGM adhesives^15-18 and pose a management challenge for both patients and healthcare professionals.¹⁹ It is important to be able to counsel prospective users of CGM/FGM with accurate information on the potential of cutaneous complications, so that realistic expectations can be set prior to undertaking this mode of glucose monitoring. However, few resources exist to guide healthcare professionals on these issues.²⁰ We therefore conducted a systematic review to identify reported cutaneous complications related to CGM/FGM use, calculate a current incidence rate, describe apparent severity and implications, as well as document any additional themes that pertain to cutaneous complications with CGM/FGM use now, and in future glucose sensing technology.

Methods

We followed reporting standards for systematic reviews²¹ (see Supplement 1 for PRISMA checklist). The protocol for this systematic review is registered (CRD42019121526).

Study Eligibility and Search Strategy

Peer-reviewed reports of clinical trials and observational studies of research or clinical practice with CGM/FGM that mention or consider cutaneous complications were eligible. Published opinions on solutions to cutaneous complications with CGM/FGM or future directions were also considered. Eligible reports were identified with an online search of Medline, Embase, and PubMed up to January 14, 2019. Search terms included (Diabetes OR T2D* OR T1D* OR GDM* OR impaired glucose OR blood glucose control OR normal glucose tolerance) AND (continuous glucose monitoring OR flash glucose monitoring OR CGM* OR FGM*) AND (skin OR cutaneous OR epidermis). No date or language limits were applied to our search. This online search was complemented by hand searching of the reference lists of relevant studies and systematic reviews. Two authors independently screened titles, abstracts, and full text articles to identify eligible studies.

Data Extraction

Data were extracted into a standardized spreadsheet used in the previous systematic reviews²² and checked by a second reviewer. We extracted the following information for each article: geographical location, study design, interventions (if relevant), inclusion and exclusion criteria, mean age, type of diabetes, type of glucose monitor, duration of device wear, and details of any cutaneous complications. Corresponding authors of articles were contacted to request additional information.

Data Analysis

We calculated an incidence rate (frequency of an event divided by total wear time) of CGM/FGM use from studies reporting subcutaneous complications. Severity was also analyzed. In addition, the data from studies identified by this systematic review are further described as they pertain to major themes: participant perspectives of these complications, potential solutions for users to mitigate or avoid cutaneous complications with CGM/FGM use, or cutaneous complications as a potential barrier to ongoing CGM/FGM use, and future developments in glucose sensing technology that may alter the future occurrence or experience of cutaneous complications.

Results

The process to identify eligible trials and studies is shown in Figure 1. Data from 46 observational studies and intervention trials of 5609 participants, and eight published opinions/reviews that discuss potential solutions and future directions were included. Identified studies were conducted in North America (50%), Europe (43%), and Asia or Australia (7%). A description of each study identified by this review is shown in Table 1. The majority (67%) of studies were conducted in the last decade.

Figure 1.

The study selection process to identify eligible trials and studies.

Table 1.

Basic Description of Studies and Trials Identified as Eligible by This Systematic Review.

ID	Participants and duration of study	Exposure	Outcome
Publications reporting cutaneous complications with CGM
Bailey et al United States²³	51 Adults followed over seven days	CGM (DexCom G4 Platinum)	Reports mild skin irritations occurred in very low frequency related to adhesives
Berg et al Denmark²⁴	120 Adults in cross-sectional analysis	CGM	Reports high frequency of cutaneous complications due to CGM with itch, eczema, and wounds being the most common issues
Berg et al Denmark²⁵	144 Children and adolescents in cross-sectional analysis	CGM	Reports high frequency of cutaneous complications related to sensor use with itch, eczema, and wound being the most common issues
Burdick et al United States²⁶	110 Children and adolescents followed over seven days	CGM	Reports skin reaction to the adhesives that resolved spontaneously
Chico et al Spain²⁷	105 Adults followed over three days	CGM (MiniMed)	Reports discomforts during the monitoring period
Christiansen et al United States²⁸	90 Adults followed over 90 days	CGM (Eversense)	Reports cutaneous complications related to sensor insertion and/or removal with their severity
Chuang et al United States²⁹	10 Adults followed over 10 hours	CGM	Reports minimal swelling and redness associated with adhesives
Cooke et al United Kingdom³⁰	404 Adults followed over 18 months	CGM (GlucoWatch G2 Biographer or MiniMed)	Reports skin reactions to GlucoWatch and discontinuations due to skin complications in GlucoWatch group
Cosson et al France³¹	48 Adults followed over 48 hours	CGM (GlucoDay)	Reports uncomplicated implantation site skin reactions which required no treatment
Deiss et al Germany³²	30 Adolescents followed over six months	CGM (Medtronic MiniMed)	Reports both sensor-wear and sensor-related skin complications
DirectNet et al United States³³	33 Children and adolescents followed over 13 weeks	CGM (FreeStyle Navigator)	Reports acute changes and nonacute changes related to sensor-insertion and sensor-wear and their severity
Duran-Valdez et al United Kingdom³⁴	40 Adults followed over five days	CGM (iPro CGM)	Reports skin irritations related to adhesives
Feig et al Europe and North America³⁵	325 Adults followed to either 34 weeks gestation (pregnant) or 24 weeks or conception (women planning pregnancy)	CGM (Guardian REAL-Time or MiniMed)	Reports skin reactions related to CGM
Garg et al United States³⁶	86 Adults followed over 21 days	CGM	Reports sensor-insertion and sensor-wear cutaneous complications and their severity
Garg et al United States³⁷	14 Adults followed over 15 days	CGM (Dexcom SEVEN or Navigator)	Reports sensor-insertion and sensor-wear cutaneous complications related to SEVEN system and Navigator system with their severity
Hoss et al United States³⁸	62 Adults followed over 14 days	CGM	Reports pain which led to sensor removal for one subject and one case of itching
Hughes et al United States³⁹	50 Adults followed over 10 days	CGM (Dexcom)	Reports minimal erythema and induration
Jadviscokova et al Czech Republic⁴⁰	22 Adults followed over nine days	CGM (Medtronic MiniMed)	Reports sensor-insertion and sensor-wear cutaneous complications and their severity
Jenkins et al Australia⁴¹	60 Adolescents followed over 32 weeks	CGM (Minimed MMT 722 Paradigm Real-Time)	Reports one severe skin reactions to sensor adhesives that led to discontinuation and one insertion site infection requiring outpatient antibiotics
Jina et al United States⁴²	10 Adults followed over 48-72 hours	CGM	Reports erythema, edema, and irritations upon device removal
Laffel United States⁴³	255 Children and adolescents followed over seven days	CGM (Dexcom G4 Platinum)	Reports mild skin irritation in some patients in the adhesive area, occurring at a low rate
Logtenberg et al Netherlands and Italy⁴⁴	12 Adults followed over six days	CGM (Paradigm REAL-Time system, Medtronic MiniMed)	Reports two sensor-wear related complications and one sensor-insertion related
Mastrototaro et al United States⁴⁵	20 Adults followed over up to two years	CGM (MiniMed Paradigm REAL-Time System)	Reports sensor-insertion and sensor-wear cutaneous complications
Secher et al Denmark⁴⁶	68 Pregnant women followed over six days	CGM (Guardian REAL-Time, Medtronic MiniMed)	Reports skin irritations related to CGM use
Tanenberg et al United States⁴⁷	128 Adults followed over 12 weeks	CGM (Medtronic MiniMed)	Reports insertion sites reactions and all were clinically mild
Tsalikian et al United States⁴⁸	23 Toddlers followed over six months	CGM (FreeStyle Navigator or Paradigm)	Reports mild and moderate skin reactions and this led to reduced CGM use during the study
The Juvenile Diabetes Research Foundation CGMS Group et al United States⁴⁹	208 Adults, 114 children and adolescents followed over 26 weeks	CGM (DexCom Seven or Minimed Paradigm Real-Time Insulin Pump and CGM or FreeStyle Navigator)	Reports two incidences of cellulitis related to sensor-use
Wong et al United States⁵⁰	20 Children and adolescents followed over seven days	CGM (CGMS Datalogger, Medtronic MiniMed)	Reports sensor-insertion and sensor-wear cutaneous complications
Yates et al Australia⁵¹	36 Children and adolescents followed over three months	CGM (Medtronic)	Reports one skin irritation at sensor site which led to withdrawal of CGM application
Zhou et al China⁵²	48 Adults followed over three days	CGM (Minimed Paradigm 722)	Reports sensor-insertion and sensor-wear cutaneous complications
Publications reporting cutaneous complications with FGM
Bailey et al United States⁵³	72 Adults followed over up to 14 days	FGM (FreeStyle Libre)	Reports sensor-insertion and sensor-wear cutaneous complications and their severity
Bolinder et al Europe,⁵⁴ subgroup analysis by Oskarsson et al Europe⁵⁵	328 Adults followed over six months	FGM (FreeStyle Libre)	Reports sensor-insertion and sensor-wear cutaneous complications, severity, and withdrawals due to cutaneous complications
Campbell et al United Kingdom, Ireland, Germany⁵⁶	76 Children and adolescents followed over eight weeks	FGM	Reports sensor-insertion and sensor-wear cutaneous complications, severity, and withdrawals due to cutaneous complications
Deja et al Poland⁵⁷	75 Children followed over 14 days	FGM (FreeStyle Libre)	Reports sensor-insertion and sensor-wear cutaneous complications and their severity
Edge et al United Kingdom⁵⁸	89 Children and adolescents followed over 14 days	FGM (FreeStyle Libre)	Reports sensor-insertion and sensor-wear cutaneous complications and their severity
Giani et al Italy⁵⁹	20 Children and adolescents followed over 14 days	FGM (FreeStyle Libre)	Reports one itching and mild skin irritations on the same participant
Haak et al Europe⁶⁰	139 Adults followed over six months	FGM	Reports sensor insertion and sensor wear cutaneous complications, severity, and withdrawals due to insertion site reactions
Landau et al Israel⁶¹	71 Children and adolescents followed over six to 12 months	FGM (FreeStyle Libre)	Reports nine cases of contact dermatitis and two discontinuations of FGM due to severe skin reactions
Scott et al United Kingdom, Austria⁶²	74 Adults followed over 14 days	FGM (FreeStyle Libre)	Reports signs and symptoms associated with sensor application or sensor site, all mild in severity
Vergier et al France⁶³	347 Children and adolescents in cross-sectional analysis	FGM	Reports skin irritations and interrupted and/or permanently stopped use of FGM
Publications reporting participant perceptions of CGM cutaneous complications
Berg et al Denmark²⁵	144 Children and adolescents in cross-sectional analysis	CGM	Reports most children continue to use CGM despite the cutaneous complications
Berg et al Denmark²⁴	120 Adults in cross-sectional analysis	CGM	Reports most adult patients continue to use CGM despite the cutaneous complications
Cooke et al United Kingdom³⁰	404 Adults followed over 18 months	CGM (GlucoWatch G2 Biographer or MiniMed)	Reports skin reactions were the most common reason of stopping CGM use
Cosson et al France³¹	48 Adults followed over 48 hours	CGM (GlucoDay)	Reports pain was nonexistent more than half of participants in the study
Engler et al United States⁶⁴	1234 Adults, 114 children in cross-sectional analysis	CGM	Reports 19%-29% of participants experienced skin irritations most times. Reason stopping CGM by adult previous users: 41% skin irritated by adhesive, 31% painful sensor application, and 10% concern about infection
Secher et al Denmark⁴⁶	68 Pregnant women followed over six days	CGM (Guardian REAL-Time, Medtronic MiniMed)	Reports women who experienced skin irritations were unlikely to use CGM again in pregnancy
Tsalikian et al United States⁴⁸	23 Toddlers followed over six months	CGM (FreeStyle Navigator or Paradigm)	Reports skin reactions led to reduced CGM use during the study
Publications reporting participant perceptions of FGM cutaneous complications
Deja et al Poland⁵⁷	75 Children followed over 14 days	FGM (FreeStyle Libre)	Reports pain was 79% smaller compared with a finger prick
Edge et al United Kingdom⁵⁸	89 Children and adolescents followed over 14 days	FGM (FreeStyle Libre)	Reports 84% of girls and boys experienced no insertion pain
Scott et al United Kingdom, Austria⁶²	74 Adults followed over 14 days	FGM (FreeStyle Libre)	Reports 89% of participants found applying sensor was less painful than fingerstick
Publications reporting solutions to CGM/FGM cutaneous complications
Englert et al United States⁶⁵	Supplemental products used to minimize adhesive or device contact with the skin such as transparent dressings, barriers, and external wraps. Site rotations and adhesive removers used to prevent rashes and dry skin
Gisin et al United States⁶⁶	Manufacturing process changes of assembling CGM to reduce skin irritations
Herman et al Belgium¹⁶	Reports sensors better tolerated with the use of thin hydrocolloid dressing
Ives et al United States⁶⁷	Recommends additional tape as a barrier between skin and transmitter tape
Kamann et al Belgium, Germany¹⁷	Reports additional plaster appears to prevent allergens from penetrating into the skin
Leelarathna et al United Kingdom¹²	Reports symptoms resolve with the use of barrier products, drug therapy, or by relocating to another area
Mamkin et al United States⁶⁸	Reports skin irritations can be minimized by placing a tape on the skin and inserting the sensor electrode through it
Messer et al United States²⁰	Recommends practical guidelines for optimal skin management, with primary emphasis on location/placement, adhesion, preventing skin reactions, and healing existing skin reactions
Wadwa et al United States⁶⁹	Reports the use of under-bandage is more hypoallergenic than the standard CGM tape.
Publications reporting future direction with CGM/FGM
Burdick et al United States²⁶	Measuring transdermal fluid glucose level through micropore technology. Adhesive use is likely
Christiansen et al United States⁶⁴	Implantable CGM. The use of adhesives is likely. One adverse event of unsuccessful removal referred to surgical specialty for removal under general anesthesia
Chuang et al United States⁷⁰	Transdermal CGM measures glucose level through a permeated skin site. Adhesive use is likely
Frontino et al Italy⁷¹	Discusses future perspectives in glucose monitoring sensors in varying degree of invasiveness
Jina et al United States⁴²	A sensor pod contains microneedle array and glucose sensor penetrating the epidermal layer. Adhesive use is likely
Ribet et al Sweden⁷²	A miniaturized sensing probe and a silicon microneedle penetrates through dermis to monitor glucose level. Adhesive use is likely
Vaddiraju et al United States⁷³	A review surveys on the current and future glucose-sensing technology

Abbreviations: CGM, continuous glucose monitoring; CGMS, continuous glucose monitoring study; FGM, flash glucose monitoring.

Cutaneous Complication Incidence

Six studies or trials with FGM^{53,54,56,59,60,62} and 13 studies or trials with CGM^{26,31,32,34,36-38,44,45,47-49,52} provided sufficient information to calculate an overall incidence rate. From 1158 participants of these trials, we identified 1090 events of cutaneous complication over 138 to 158 accumulated years of wear time. The cutaneous complication event rate was 0.13 to 0.15 for every week of wear-time, indicating one event every eight weeks. Reported occurrence varied considerably between trials with higher rates when researchers inspected the site (1.4 events per week of wear time)⁵³ than when patient reported adverse events (0.04 events per week of wear-time).²⁶ Many papers reported only moderate to severe events. The most common cutaneous reaction was erythema (55%), followed by itching/pruritus (11%) and induration (9%). A full summary of cutaneous complication frequency by type is shown in Table 2. Studies^{27,29,36-38,40,41,44,49,50,52,55,56,60,61} reported more adhesive or wear-associated cutaneous complications (80%) (eg, erythema and itch) than direct insertion-related complications (20%) (eg, bruising or bleeding).

Table 2.

Reported Cutaneous Complications Related to Continuous Glucose Monitoring/Flash Glucose Monitoring Use.

Issue	N trials and participants	N complications	% of Each issue
Sensor wear related cutaneous complications
Erythema	Seven trials of 584 people	319 Issues over 38.5 weeks	55.2
Pruritus/itching	Five trials of 548 people	65 Issues over 35.3 weeks	11.2
Induration	Three trials of 549 people	49 Issues over 33 weeks	8.5
Edema	Four trials of 436 people	40 Issues over 29.15 weeks	6.9
Rash	Two trials of 328 people	37 Issues over 32 weeks	6.4
Bruising	Five trials of 552 people	33 Issues over 37.5 weeks	5.7
Allergic reaction	Four trials of 388 people	25 Issues over 65.29 weeks	4.3
Skin infection	Four trials of 170 people	Four issues over 27.1 weeks	0.7
Dry skin	Two trials of 96 people	Three issue over nine weeks	0.5
Cellulitis	One trial of 322 people	Two issues over 26 weeks	0.3
Collection	One trial of 76 people	One issue over eight weeks	0.2
Sensor insertion related cutaneous complications
Pain	Seven trials of 661 people	87 Issues over 37.12 weeks	61.7
Bleeding	Three trials of 426 people	53 Issues over 33.29 weeks	37.6
Hematoma	One trial of 76 people	One issue over eight weeks	0.7

Several studies reported severity of cutaneous complications.^{36,37,40,47,48,55,56,59,60,62} Overall, 78.6% of cutaneous complications were rated as mild, 19.8% were moderate, and only 1.5% were severe. Skin reactions or irritations were the most common reason for participants to withdraw from studies.^{30,41,51,54,60}

Data from observational studies indicate that more than 70% of participants have experienced cutaneous complications related to CGM/FGM use at some point, with itch, eczema, and insertion wounds the most commonly reported complications.^24,25,63

Participant Perspectives of Cutaneous Complications

Several studies assessed participant perspectives toward the use of CGM/FGM with questionnaires,^{24,25,30,31,46,48,53,57,58,62,65} primarily comparing CGM/FGM use with capillary blood glucose testing.^{31,46,48,53,57,58,62,64} Many studies indicated that both adults and children report less pain and bleeding associated with CGM/FGM use than capillary blood glucose testing. Sensor insertion pain or bleeding was not considered a deterrent of use for the majority of individuals.^31,53

Cutaneous complications are often given as a reason for discontinuing CGM/FGM use. Skin irritation due to adhesives was given as the predominate reason for adults (42%)⁶⁴ and children (40%)⁴⁸ to stop CGM/FGM use. Two studies reported that many children and adult patients continue to use CGM despite experiencing cutaneous complications,^24,25 but concern about infection accounted for 10% of the previous adult CGM/FGM users discontinuing CGM.⁶⁴

Potential Solutions

Data on this topic were largely from reviews or published opinions. The most recent of these provides a detailed discussion on the current solutions for preserving skin integrity for chronic device use for those wanting more detail.⁷⁴ In brief, this process should begin with setting appropriate expectations, and an assessment of current and past skin health.⁷⁴ Once that has been done, the current solutions for reducing cutaneous complications with CGM/FGM use relate to careful consideration for appropriate device placement, minimizing adhesive or sensor contact with the skin,^65,67 or changing the adhesion process of CGM components.⁶⁶

In practical terms, options include adequate drying prior to insertion and the use of various supplemental products such as adhesive barriers, tackifiers (to improve adhesion), or possibly off-label steroid sprays prior to insertion for those with known prior reactions (eg, fluticasone).^{16,17,20,65,68,69} To minimize adhesive exposure, an external wrap (eg, cohesive bandage) to secure sensors without the use of additional adhesives can also be used. Dressings can also be trimmed to only cover sensor adhesive areas and not the transmitter, so as to prevent moisture buildup. Site rotations, adhesive remover, and the use of steroid cream and antihistamines have all been reported to prevent or manage rashes and dry skin.⁷⁴ Careful sensor removal so as to avoid further skin damage cannot be overemphasized; and if an injury is present, postremoval skin care for recovery may be necessary.⁷⁴ In addition, FGM/CGM suppliers have reportedly modified manufacturing to reduce skin reactions, however, such changes have not removed the need for an adhesive barrier between skin and device.⁶⁶

Future Technology to Mitigate Cutaneous Complications

Several publications have considered new technologies in glucose sensing that may modify the risk of cutaneous complications.^71,73 These technologies can be considered by their degree of invasiveness.

Invasive

Implantable CGM (such as the recently approved Eversense device) sits under the skin surface and currently last for up to 90 days,²⁸ reducing the risk of cutaneous complications associated with changing sensors. An adhesive patch is then used to secure the transmitter over the sensor. Complications related to sensor insertion and removal (bruising, erythema, and pain or discomfort) have been reported.²⁸ In this pivotal trial for regulatory approval, one participant of 90 had to be referred to surgical specialty for removal under general anesthesia. No skin reactions were reported due to the adhesive patch.

Minimally invasive

Microneedle-based CGM involves two components: a miniaturized sensing probe and a silicon micro-needle⁷² or an array of silicon microneedles⁴² which penetrate the dermis⁷² or epidermis⁴² to monitor glucose level as compared with hypodermis, as in the current CGM/FGM devices. Adhesive is used to secure the device to the skin. Skin complications such as erythema and edema have been observed at the sensor site upon device removal.⁴² This technology is currently not approved for general use and requires further trials and development to assess accuracy and safety.

Noninvasive

Transdermal CGM continuously measure glucose through ultrasonically permeated skin sites.⁷⁰ Alternatively, transdermal fluid glucose is measured by producing micropores in the skin and drawing transdermal fluid to the glucose sensor,²⁶ or with electrochemical sensing of the skin surface.⁷⁵ The use of adhesives for these options are likely, although not specifically mentioned in the current literature. Cutaneous complications have yet to be reported from the available studies on this emerging glucose-sensing technology.

Discussion

This systematic review and the number of studies available for inclusion highlight a significant interest in CGM/FGM technology for modern diabetes management. To our knowledge, this is the first systematic review to synthesize and focus on the occurrence of cutaneous complications in studies with CGM/FGM devices. As reported in the available trials, we determined an overall cutaneous complication incidence rate of one event/eight weeks wear time. Most complications were minor skin reactions/irritations related to wear time. Few participants in these trials ceased use due to these complications.

There was a great deal of variability in the incidence rate of cutaneous complications as reported in the individual trials and between trials where cutaneous adverse events were patient vs investigator reported. In addition, the primary objectives for these trials were not to examine cutaneous complication frequency, and most were of relatively short duration. All these factors suggest that not all minor or low severity complications have been reported as adverse events during the published trials, indicating that our trial-reported incidence rate is likely an underestimate of the true real-world incidence. Supporting this possibility, the data from observational studies indicate a likely high prevalence of experiencing cutaneous complications.^24,25 To fully understand this important issue and allow developments for prevention and treatment, consistent reporting, including standardized definitions of severity, is required, and future reporting of trials should identify all occurrences of cutaneous complications by type and severity so as to better inform on this issue.

Crucial for perspective on this topic is the clearly increasing rates of CGM use worldwide^6,13 and the overall high satisfaction seen with users of CGM/FGM in the available literature.^76,77 These factors combined with our review findings would suggest that the perceived benefits to the user largely outweigh the downsides of cutaneous complications. Further solutions for prevention and management of cutaneous issues are required,²⁰ as the next generation of CGM still largely relies on both adhesive use and penetrating the skin barrier. Regarding the current adhesives, varying degrees of contact dermatitis can occur depending on the manufacturer, and reactions to isobornyl acrylate, colophonium, ethyl cyanoacrylate, and N,N-dimethylacrylamide have all been reported.^78-80 There is also a recognized need for manufacturing changes to improve breathability and reduce trapped moisture that contribute to skin reactions with the current technologies.⁸¹ Further research into hypoallergenic adhesives or the long-term possibility of glucose sensing without penetrating the skin barrier are necessary to reduce these barriers to CGM/FGM use. Integration of glucose sensing with insulin delivery may also decrease the risk of cutaneous complication by reducing the number of points of contact with adhesive.

Our review has several strengths. We have followed best practice guidelines for conducting and reporting of systematic reviews. Given the nature of our research question, we have presented results of our review under four themes, each necessary for the consideration of cutaneous complications with CGM/FGM use. Our search strategy also recognized many recent conference abstracts that have not yet resulted in a peer-reviewed publication, indicating the growing use of CGM/FGM, and therefore, future relevance of our review. Our review also has limitations. Not all trials utilizing CGM and FGM report adverse events, let alone cutaneous complications. Our incidence rate is based on trials that did report cutaneous complications and therefore may introduce bias into our estimates. Further, data on the specific type and severity of complications were not often available. We believe that this limitation can be minimized in further considerations of this topic should publications routinely report cutaneous complications with diabetic devices and emerging technologies.

Conclusion

This systematic review of the CGM/FGM literature focused on cutaneous complications highlights an overall trial-reported incidence rate of one cutaneous complication for every eight weeks of wear-time. These were typically mild in severity and resulted in minimal discontinuation. However, this rate is likely an underestimate, especially for mild events. There is a need for improved routine and consistent reporting of CGM/FGM related cutaneous complications in future CGM/FGM trials; as well for improved techniques and technology to improve the patient experience and reduce the future impact and occurrence of cutaneous complications.

Supplemental Material

MOHD_ASARANI_Supplement_1 – Supplemental material for Cutaneous Complications With Continuous or Flash Glucose Monitoring Use: Systematic Review of Trials and Observational Studies

Supplemental material, MOHD_ASARANI_Supplement_1 for Cutaneous Complications With Continuous or Flash Glucose Monitoring Use: Systematic Review of Trials and Observational Studies by Nurul A. Mohd Asarani, Andrew N. Reynolds, Sara E. Boucher, Martin de Bock and Benjamin J. Wheeler in Journal of Diabetes Science and Technology

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Department of Women’s and Children’s Health and the Department of Medicine, University of Otago.

ORCID iDs

Nural A. Mohd Asarani

Andrew N. Reynolds

Sara E. Boucher

Supplemental Material

Supplemental material for this article is available online.

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