The Steno2tech CGM study is a single-centre, prospective, randomised, open-labelled, three-armed study in adults with T2D treated with insulin comparing the use of RT-CGM (without peer support (group A), RT-CGM with peer support (group B)) with standard SMBG measurements (group C). Each participant will be in the study for 12 months.

Recruitment will take place at the outpatient clinic at Steno Diabetes Center Copenhagen (SDCC), Denmark. Inclusion criteria are: age ≥18 years, clinical diagnosed T2D with duration ≥1 year, treated with insulin injections at least once daily, ≥1 year on top of diet and exercise recommendations (can be additionally treated with one or more different oral antidiabetic drugs (except sulfonylurea (SU)) and/or glucagon-like peptide 1 analogues), HbA1c >58 mmol/mol and attending the outpatient clinic at SDCC ≥1 year.

Exclusion criteria are: inability to understand the patient information, missing informed consent, treatment with SU during the last 3 months before study starts, new antidiabetic treatment the last 3 months, use of systematic corticosteroids, severe visual impairment, severe skin allergy for adhesive tape to the patch of CGM or other skin condition that inhibits the use of a CGM device, comorbidity which does not allow lowering of HbA1c to 53 mmol/mol (7.0%), hypoglycaemic unawareness, impaired renal disease with estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m², conditions that impact the stability of an HbA1c measurement (chronic liver disease, haemoglobinopathy, anaemia and so on), known or suspected alcohol or drug abuse, enrolled in another clinical study or pregnancy, intention to become pregnant, breast feeding or not using adequate contraceptive methods. Furthermore, persons with prior experience with Flash Glucose Monitoring (Libre) or CGM, will be excluded, as prior use could potentially bias the results.

We aim to recruit a total of 100 participants. Recruitment for the study will begin August 2020 and will end in July 2021. Final 12-month follow-up is anticipated to be in August 2022.

Participants will be randomised to three different study groups (2:1:2), A CGM group, B CGM group using peer support and C the control group, using REDCap (REsearch Data CAPture software), a secure web-based application designed to support research data capture.24 The allocation sequence will be centrally prepared by a person without relation to the specific study and generated using www.sealedenvelope.com.

After randomisation, the participants in the three study groups will attend a 3-hour training course with different contents depending on the group allocation. The aim of this training course is to ensure that the participants have the knowledge, support and confidence to work collaboratively with their HCPs to increase TIR and HbA1c. The training courses will be of similar length to avoid the influence of more time with the investigator/HCPs on outcome for the CGM group A versus the control group C. All participants will receive education on health behaviour, the influence of different food items and exercise on glucose levels and how to measure SMBG correctly. Furthermore, participants in group A and B (intervention) will receive a CGM education and training session led by the study investigator, including interactive and hands-on, using case studies. The training session will include spoken and written instructions on how to insert and wear the CGM device and how to interpret the CGM information to better understand the relation between participants’ blood glucose and their diabetes self-management.

After the training course, participants in group B will get an email on the peer-support set-up, concept and content. The participants will be asked to share their wishes for topics to be discussed during the following peer-support sessions. The peer support will be facilitator-led by the primary investigator with peer exchange in group sessions (three sessions over the study period, 3 hours per session) with four to six participants in every group. The approach will be participatory and adaptable to allow flexibility in the content of the peer-support sessions and involve customised use of participatory methods, that is, dialogue tools and exercises from ‘In Balance with Chronic Illness: Tools for Patient Education’ from SDCC.25 The first session will include the involvement of participants in planning the content of the three peer-support sessions and a discussion on confidentiality among the participants.

All participating HCPs will attend a CGM education and training session, similar to the participants. The aim of the CGM training course is to ensure that the HCPs have the knowledge and support and confidence to work collaboratively with study participants to increase TIR and decrease HbA1c.

Included outcome measures are shown in the following box 1.

At the screening visit, informed consent will be retrieved, and inclusion and exclusion criteria will be reviewed. The following baseline data will be recorded: sex, age, highest education level, civil status, occupation, race/ethnicity, diabetes duration, total daily insulin dose (average of previous 7 days) and number of insulin injections per day, frequency and mean of SMBG/day, number of severe hypoglycaemia events in previous 12 months, hypoglycaemia awareness, allergies, medical history, medications prescribed (use of non-insulin glucose-lowering medication), height, weight, BMI, blood pressure and heart rate. During the screening visit, hypoglycaemia awareness will be evaluated using Pedersen-Bjergaard et al classification of hypoglycaemia awareness.26 27 According to the exclusion criteria, a potential participant will be excluded in case of unawareness.

Participants will be advised to document any severe hypoglycaemic episodes throughout the study in a glucose diary provided. Episodes of severe hypoglycaemia will be defined as ‘a hypoglycaemic event serious enough to require the help of another person’ (self-reported).

Blood samples during the study will be collected for analysis of HbA1c, blood glucose, creatinine, eGFR, alanine aminotransferase, thyroid stimulating hormone, cholesterol, triglycerides, low-density lipoprotein and high-density lipoprotein. Urine samples will be analysed for albumin, creatinine and Urine-Human Chorionic Gonadotrophin to test for pregnancy (U-HCG) where relevant.

The following standardised validated PRO questionnaires will be provided at visits 1, 7 and 10: The WHO Five Well-Being Index,28 the Diabetes Distress Scale,29 the revised short-form Hypoglycaemia Fear Survey,30 the Glucose Monitoring Satisfaction Scale,31 the Diabetes Treatment Satisfaction Questionnaire32; status questionnaire for baseline characteristics and a change questionnaire for intervention end point measurements,33 34 the Swedish National Board of Health and Welfare questionnaire for assessing Physical Activity,35 a Danish questionnaire inspired by the Perceived Dietary Adherence Questionnaire36 and a Danish questionnaire on Medical Adherence.37

Participants in all three groups will wear a blinded CGM (DexCom G6) for a 10-day period before randomisation, after 30.5 weeks and after 58.5 weeks. The participants will receive both spoken and written information about the blinded CGM, instructions on how to insert and wear the CGM, skin preparation and observation of skin reactions.

Participants in the two CGM groups will wear the open CGM according to treatment, and participants in all of the three groups will wear the blinded CGM to measure the effect of the treatment.

There are five clinical follow-up visits (visits 4, 5, 7, 8, 10) planned during the 60 weeks’ study period (see table 1). During these visits, SMBG or CGM data will be uploaded via Diasend and data will be collected.

In general, during the study, the goal is to achieve HbA1c 53 mmol/mol or below and most possible glucose values measured with CGM or SMBG in the range 3.9–10 mmol/L with all possible means. The treatment intensification will be depending on: patterns from downloaded SMBG/CGM, history of medication since last visit, issues regarding exercise and food intake, and episodes of hypoglycaemia and symptoms of hyperglycaemia. For each group, a group-specific SOP for the treatment intensification will be used, based on the existing guidelines and procedures in the outpatient clinic. The treatment intensification will be done by a specialist in diabetology specifically experienced in treating T2D. The patterns they observe on the downloads and the specific actions they are recommending in response to the patterns will be recorded.

The data management is performed in accordance with the General Data Protection Regulation and approved by the Danish data protection agency (J-2020-100). All information on study participants is protected according to law on processing of personal data and the law of health. The electronic study database in REDCap is password protected and located on the hospital network server which is continuously backed up. All information on paper that is personally identifiable will be kept in a locked filing cabinet in a double-locked office. Only the study sponsor and investigators will have access to the study database.

A sample size of 74 (37 in each group (A+C)) was calculated to have 90% power to detect a difference in mean time in target glycaemic range, TIR (3.9–10.0 mmol/L) between group A and C of 75 min/day equivalent to a 5% increase in TIR, which is associated with clinically significant benefits,4 SD of 100 min11 and a 2-sided α-level of 0.05. Sample size is increased to 80 (40 in group A+C) to account for a potential dropout of approximately 10%. In this study, the effect of peer support will be considered hypothesis-generating for later studies, and 20 participants in group B will be included for that purpose.

Blinding of the study will not be possible as the treatment advice is dependent on the different treatments in the groups. Participant characteristics at baseline will be summarised for each group. Comparable statistics with continuous outcome will be calculated by t-test for parametric and Wilcoxon rank sum for non-parametric continuous variables, and Fisher’s exact test for categorical variables. Changes in primary and secondary outcomes over the intervention period and effects of the treatments will be modelled by linear mixed-effects models with a patient-specific random intercept to account for the correlation of repeated measurements within patients. These will include the interim measurements at 6 months. The p values for secondary outcomes will be corrected by the Benjamini-Hochberg method for multiple comparisons.

Analysis will be performed on an intention-to-treat basis. Furthermore, per-protocol analysis will be performed, including participants in group A and B having used the CGM device as instructed for at least 80% of the entire study period and participants in group B having participated in at least two out of three peer-support sessions.

Missing data will be handled with multiple imputations. Furthermore, dropout rates and characteristics on non-participants including reasons will be examined if informed consent is obtained. Statistical significance will be inferred at a 2-tailed p value of 0.05 with a CI on 95%.

To examine the education concept of the training course prior to the start of the study, we invited a group of patients at SDCC to give us their considerations on our training courses. We adjusted the course concepts considering their input. Likewise, the peer-support concept and contents and all written information were examined by a group of patients at SDCC to secure correct understanding and user influence here on.

At the end of the study, the participants will be asked to evaluate the study, study procedures, education and so on, including interviews and/or questionnaires, on preferred future treatment.