Protocol for a 1‐year randomised, controlled, parallel group, open‐label trial on the effects and feasibility of time‐restricted eating in individuals with type 2 diabetes‐ The REStricted Eating Time in the treatment of type 2 diabetes (RESET2) trial

Abstract

Aim

Time‐restricted eating (TRE) limits the time for food intake to typically 6–10 h/day without other dietary restrictions. The aim of the RESET2 (the REStricted Eating Time in the treatment of type 2 diabetes) trial is to investigate the effects on glycaemic control (HbA_1c) and the feasibility of a 1‐year TRE intervention in individuals with overweight/obesity and type 2 diabetes. The aim of the present paper is to describe the protocol for the RESET2 trial.

Methods

RESET2 is a randomised, controlled, parallel‐group, open‐label trial. One hundred and sixty individuals with type 2 diabetes (HbA_1c >53 mmol/mol (>7.0%)), and Body Mass Index ≥25 kg/m² will be randomised to standard care plus TRE, or to standard care and habitual living. Both the intervention and control group will follow standard diabetes care including regular clinical visits 3–4 times/year. The intervention is divided into two periods: (1) a 3‐month TRE period with a fixed eating window with a self‐selected timing to obtain data from the participants' experiences with TRE and (2) a 9‐month individually adjusted TRE period. Participants in the TRE group will be instructed to reduce their eating window by a minimum of 3 h/day compared to the habitual eating window and with an eating window of 8–10 h/day. Test days will be scheduled at baseline, after 3 months and after 1 year. The primary outcome is HbA_1c (evaluated 3 months and 1 year after randomisation) and secondary outcomes are body weight, fat mass, continuous glucose monitoring derived time‐in‐range and use of antidiabetic medicine (evaluated 1 year after randomisation). Additionally, we will conduct a process evaluation to assess whether the TRE intervention functioned as hypothesised.

What's new?

• To date, only a few short‐term studies have investigated time‐restricted eating in individuals with type 2 diabetes.

• The randomised‐controlled RESET2 trial investigates the effects of a 1‐year time‐restricted eating intervention on glycaemic control in individuals with type 2 diabetes.

• The RESET2 trial is based on a comprehensive needs assessment study and pilot study and is designed to account for potential barriers and motivational factors in individuals with type 2 diabetes.

1. INTRODUCTION

Type 2 diabetes is associated with an increased risk for cardiovascular and cognitive diseases. ¹ , ² , ³ Beyond pharmacological treatments, current strategies to reduce body weight and improve glycaemia include energy‐ and carbohydrate‐restricted diets and increased physical activity. ⁴ Unfortunately, implementation and maintenance of lifestyle changes is difficult for many, and there is a strong unmet need for acceptable, feasible and sustainable lifestyle regimens to support individuals with type 2 diabetes in attaining and maintaining weight loss and improved glycaemic control. Time‐restricted eating (TRE) is a type of intermittent fasting that reduces the window for food intake to typically 6–10 h/day without other dietary restrictions and has shown promising effects on body weight, glucose metabolism and cardiometabolic health in individuals at high risk of type 2 diabetes. ⁵ , ⁶ , ⁷ To date, only a few studies have investigated TRE in individuals with type 2 diabetes, ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴ and most studies have a short duration and a non‐randomised design. Previously, we have reported a high prevalence of late‐evening food intake along with a long eating window amongst individuals with type 2 diabetes, ¹⁵ indicating a potential for TRE in this group. TRE has been shown to be a safe, feasible and acceptable intervention in individuals with overweight, obesity, prediabetes and type 2 diabetes. ¹⁶ , ¹⁷

However, TRE may be difficult to implement for some people and major barriers have been related to social and family life, daily habits as well as physical and mental issues. ¹⁷ Determinants of adherence included the possibility to drink energy‐free beverages outside the eating window, provision of professional support and individual influence on the timing of the eating window. ¹⁷ However, little is known about the long‐term effects, safety and feasibility of TRE in individuals with type 2 diabetes.

The REStricted Eating Time in the treatment of type 2 diabetes (RESET2) project includes a TRE intervention designed to account for potential barriers and motivational factors in individuals with type 2 diabetes. The RESET2 project consists of three phases: (1) a needs assessment study, (2) a pilot study and (3) a randomised controlled trial (RCT) (present protocol).

The needs assessment study (phase 1) included interviews and workshops with individuals with type 2 diabetes, their relatives and health care professionals. ¹⁸ The findings suggested three key intervention components when designing a TRE intervention. These were (1) a two‐phase design with a short strict TRE period, followed by a long period focusing on tailoring TRE to individual needs, (2) individual guidance and support to plan and initiate TRE and (3) individual adjustments to promote TRE adherence and maintenance for example, energy‐free beverages outside the eating window, and ‘days off’ from TRE. ¹⁸

In the pilot study (phase 2), we investigated the feasibility of a 12‐week 10‐h TRE intervention targeting individuals with type 2 diabetes to inform the RCT design. The participants initially followed 8 weeks of strict TRE with a self‐selected 10‐h eating window to obtain lived experiences with TRE, followed by a 4‐week TRE period with individual adjustments and support options (Termannsen et al., unpublished). The pilot study informed the design of the TRE intervention described in the present protocol.

2. OBJECTIVES

The primary objective of the RESET2 trial (phase 3) is to investigate the effects of TRE on haemoglobin A1c (HbA_1c) evaluated at 3 months and 1 year after randomisation, in individuals with overweight/obesity and type 2 diabetes. Secondary objectives are to investigate changes in body weight, fat mass, continuous glucose monitoring (CGM) derived time‐in‐range and use of antidiabetic medicine evaluated at 1 year after randomisation (changes in all secondary outcomes after 3 months intervention are defined as descriptive outcomes). Furthermore, we will describe changes in cardiometabolic risk factors, food preferences and reward, cognition, dim light melatonin onset and patient‐reported outcomes including self‐rated health and well‐being, physical activity, diabetes distress, food intake and sleep quality. Additionally, we will also conduct a process evaluation to assess whether the intervention functioned as hypothesised by examining: (1) the implementation of key components, the acceptability of health care professionals delivering the TRE intervention, and contextual influences and (2) participants' acceptability of key intervention components, along with their experiences of challenges and facilitators in following TRE.

3. HYPOTHESES

We hypothesise that TRE added to standard diabetes care will be superior in reducing HbA_1c at both 3 months (hypothesis 1) and 12 months (hypothesis 2) in individuals with overweight/obesity and type 2 diabetes.

4. MATERIALS AND METHODS

4.1. Trial design

This single‐centre, randomised, controlled, parallel‐group, open‐label trial will include 160 individuals with overweight/obesity and type 2 diabetes to 1‐year standard care plus TRE, or standard care and habitual living (Figure 1). The TRE intervention consists of a 3‐month strict TRE period followed by a 9‐month individually adjusted TRE period. The trial will be conducted at Steno Diabetes Center Copenhagen (SDCC), Denmark. Both the intervention and control group will follow standard diabetes care at SDCC including regular clinical visits 3–4 times/year with endocrinologists, nurses and/or dieticians. In case of challenges with the recruitment of participants from SDCC, participants will be recruited from outside SDCC and will continue standard diabetes care by their general practitioners. The trial consists of six visits with up to 1‐year follow‐up (Figure 1).

FIGURE 1.

The RESET2 RCT trial design: (V0) oral study information, signing of informed consent, screening for eligibility and initiation/collection of free‐living measurements (10 days before V1); (V1 + V3 + V5) regular study visits at baseline, after 3 months and after 1 year and (V2 + V4) short visits to initiate/collect free‐living measurements (10 days before V3 and V5). MRI, magnetic resonance imaging; TRE, time‐restricted eating; V, visit.

4.1.1. The RESET2 MRI sub‐study

Forty (20 in each group) out of the 160 participants will be enrolled in the RESET2 magnetic resonance imaging (MRI) sub‐study involving assessments of brain insulin resistance and circadian phase before and after 3 months of strict TRE or standard care only. MRI's will be performed at Copenhagen University Hospital Rigshospitalet‐Glostrup on separate days shortly before V1 and V3 (Figure 1). Dim light melatonin onset samples will be collected at home by the participants 2–3 days before MRI scans.

4.2. Eligibility criteria

The study population will include women and men (≥18 years) diagnosed with type 2 diabetes, and with HbA_1c >53 mmol/mol (>7.0%), BMI ≥25 kg/m² and a habitual eating window ≥12 h/day. People using fast‐acting insulin and combination insulin products will be excluded, with no additional restrictions regarding medication use, diabetes duration or disease status. See Table 1 for a full list of eligibility.

TABLE 1.

Eligibility criteria.

Inclusion criteria

Type 2 diabetes with haemoglobin A1c (HbA1c) >53 mmol/mol (>7.0%) Body Mass Index ≥25 kg/m2 Age ≥18 years Habitual eating window ≥12 h/day (incl. foods/snacks and energy‐containing beverages)

Exclusion criteria

Bariatric surgery or planned bariatric surgery within the study duration Use of fast‐acting insulin and combination insulin products Habitual use of continuous glucose monitoring (CGM) devices A wish to adhere to Ramadan For women: current/planned pregnancy or lactation Alcohol or drug abuse (judged by the investigator) or treatment with disulfiram Severe hypoglycaemia within the last year (Severe hypoglycaemia, as defined by the American Diabetes Association (ADA), denotes severe cognitive impairment requiring external assistance for recovery) Inability to understand written and oral information in Danish Unable or unwilling to adhere to time‐restricted eating; for instance, due to competing medical conditions Medical condition which, based on investigators' assessment, challenges participation including but not limited to severe heart, vascular or lung disease, cancer, chemotherapy, psychiatric, gastrointestinal, rheumatic or endocrine diseases Concomitant participation in other intervention studies Inability to perform neuropsychological tests (e.g., severe vision and hearing impairment that cannot be improved with aids such as glasses and hearing aids or language barrier) For the sub‐study only: Magnetic resonance imaging (MRI) contraindications based on the MR department's exclusion criteria including pacemakers or other implanted electronic devices, implanted metal objects not compatible with MRI scanning and severe claustrophobia Participants who do not wish to be informed about accidental findings by MRI

4.3. Recruitment of participants

Participants will be recruited from the outpatient clinic at SDCC where potential participants will be identified in two ways: (1) through electronic health records and electronic invitation or (2) at regular clinical visits at SDCC. A pre‐screening telephone interview will be performed, where the potential participants will receive information about the study and inform the health care professional about current HbA_1c, BMI and habitual eating window. The pre‐screening aims to reduce the number of screen failures. At the screening visit (V0), potential participants will receive thorough study information. Hereafter, they can provide oral and written informed consent before initiating a full assessment of eligibility.

In case of a low recruitment rate from SDCC, we plan to recruit participants treated in primary care in municipalities in the Greater Copenhagen area through flyers or advertisements, or using the webpage www.trialtree.dk.

4.4. Randomisation

After completion of baseline measurements at V1, participants will be randomised to either standard care plus TRE, or standard care and habitual living in a 1:1 ratio using block randomisation (block sizes of 4, 6 and 8). The trial includes two randomisation lists: one list for the 120 participants included only in the main trial and another list for the 40 participants in the main trial plus the MRI sub‐study. Randomisation lists will be generated by an external researcher using R version 4.3.0 (blockrand‐package, version 1.5, https://cran.r‐project.org/web/packages/blockrand/blockrand.pdf), and will be kept in sealed envelopes. Health care professionals will enrol and allocate participants to interventions. After allocation, both participants and project staff will be unblinded to the randomisation due to practical reasons. However, data analysts will be blinded during the statistical analysis of the primary and secondary outcomes.

4.5. Trial outcomes and methods

4.5.1. Primary outcome

The primary outcome, HbA_1c (mmol/mol (%)), will be evaluated after 3 months and 1 year of intervention (Table 2).

TABLE 2.

Schematic overview over trial visits.

Visit	V0	V1	V2	V3	V4	V5
	10 days before V1	Baseline	10 days before V3	3 months after V1	10 days before V5	1 year after V1
Participant information
Signing of informed consent	X
Assessment of inclusion and exclusion criteria	X
Medical history	X
Use of antidiabetic medicine	X	X		X		X
Overall medication use (e.g., lipid‐lowering and blood pressure‐lowering medication)		X		X		X
Clinical assessments
HbA1C	X	X		X		X
Weight	X	X		X		X
Height	X
Body Mass Index	X	X		X		X
Continuous glucose monitoring	X		X		X
Dietary intake	X		X		X
Eating window	X		X		X
Waist/hip circumference and waist/hip ratio		X		X		X
Body composition (DXA scanning)		X		X		X
Blood pressure and resting heart rate		X		X		X
Fasting blood sample for assessment of hormones involved in glucose metabolism and appetite control, lipid metabolism, markers of ketones and inflammation and markers of liver and kidney function		X		X		X
Subjective appetite (Electronic visual analogue scales (VAS)) 19		X		X		X
Food preferences and food reward		X		X		X
Liver function (Fibro scanning)		X		X		X
Cognitive function		X		X		X
Brain insulin resistance (MRI scanning) (participants in the sub‐study only) a	X		X
Dim light melatonin onset (participants in the sub‐study only) a	X		X
Questionnaires b
Sociodemographic characteristics	X
Eating Disorder Examination Questionnaire, questions 13 and 14 (EDE‐Q 6.0) 20	X		X		X
Physical Activity Scale (PAS1) 21	X		X		X
Pittsburgh Sleep Quality Index (PSQI) 22	X		X		X
Morningness‐Eveningness Questionnaire, question 19 (MEQ) 23	X		X		X
Alcohol intake, questions 19–28 in the Danish National Health Survey 24	X		X		X
Night Eating Questionnaire (NEQ) 25	X		X		X
Dutch eating behaviour questionnaire (DEBQ) 26	X		X		X
Major Depression Inventory (MDI) 27	X		X		X
Epworth sleepiness scale (ESS) 28	X		X		X
Cognitive Failures Questionnaire 29	X		X		X
Sense of Coherence Scale (SOC‐13) 30	X		X		X
Social relations and social support, questions 46 + 48 in the Danish National Health Survey 24	X		X		X
Sexual functioning/wellbeing, question 79 in the Danish National Health Survey, 24 and questions 46 + 63–65 in the Danish PRO scheme (diabetes) 31	X		X		X
Diabetes distress (PAID‐5 scale) 32	X		X		X
Process evaluation‐related activities
Individual interviews (subgroup of participants randomised to TRE)						X
Focus group interviews (subgroup of participants randomised to TRE)						X
Interviews with health care professionals delivering the TRE intervention		X		X		X

Abbreviations: DXA, dual‐energy X‐ray absorptiometry; HbA_1c, haemoglobin A1c; MRI, magnetic resonance imaging; TRE, time‐restricted eating; V, visit.

^a Before V1 and V3.

^b Questionnaires filled out at home before V1, V3 and V5.

HbA_1c was selected as the primary outcome because it is the primary method to assess glycaemic status in both clinical practice and research settings, and HbA_1c is strongly associated with the risk of developing diabetes‐related complications. ³ , ³³ HbA_1c will be measured using Atellica CH 930 (Siemens Healthineers, Erlangen, Germany).

4.5.2. Secondary outcomes

The secondary outcomes, body weight (kg), fat mass (kg), time‐in‐range for glucose levels (% 3.9–10.0 mmol/L) and use of antidiabetic medication will be evaluated after 1 year of intervention (Table 2).

Body weight will be measured in a fasted state to the nearest 0.1 kg using a digital scale (SECA mBCA 515, Seca gmbh & co. kg, Hamburg, Germany) whilst participants will be wearing light clothes/underwear. Fat mass (kg) will be measured in a fasted state by whole‐body dual‐energy X‐ray absorptiometry (DXA) (Lunar IDXA, GE Medical Systems Ultrasound & Primary Care Diagnostics, Wisconsin, USA). Time‐in‐rage will be assessed by continuous glucose monitoring (CGM) across 10‐day periods. The CGM device will be inserted on the back of the upper arm (Dexcom G7, Dexcom, California, USA). The results of the CGM measurements will be blinded to participants. Information about diabetes medication will be obtained from electronic health records.

4.5.3. Exploratory/descriptive outcomes

Exploratory/descriptive outcomes including a variety of metabolic and behavioural outcomes potentially associated with the intervention will be evaluated after 3 months and 1 year of intervention (see Table 2 and Supporting Information—Data S1 for further details).

4.5.4. MRI sub‐study outcomes

Descriptive/exploratory outcomes including brain insulin resistance and dim light melatonin onset will be evaluated after 3 months of intervention (see Table 2 and Supporting Information—Data S1 for further details).

4.6. Intervention

4.6.1. Intervention group

The intervention group will follow the 1‐year TRE intervention, divided into two periods, added to standard care as shown in Figure 1.

Three months of strict TRE intervention

The intervention consists of a 3‐month strict TRE period, where participants follow the same eating window daily with minimal support to obtain lived experience with TRE (Figure 1).

Conversation and introduction to TRE intervention

Participants in the TRE group will discuss their daily lives, perceptions and expectations with a health care professional. This conversation will cover motivation, needs, barriers and previous experiences with dietary interventions and weight loss. Participants will receive individual support to adapt their daily routines to TRE using the ‘My Day’ dialogue tool, visualising a 24‐h schedule where activities such as eating, drinking, work, sleep, medication, social activities and exercise are illustrated to explore current habitual living and facilitate optimal scheduling of the eating window. ³⁴

Description of the eating window

Participants will be instructed to reduce their eating window by a minimum of 3 h compared to habitual eating and with an eating window of 8–10 h. The timing of the eating window will be self‐selected but should be placed between 6 AM and 8 PM and be kept consistent across the 3 months. There will be no restrictions regarding the type and amount of food and beverages during the window.

Adjustment and social support options

Adjustment and social support options available from baseline to end of intervention are shown in Figure 2.

FIGURE 2.

Overview of adjustments and support options during the 3 months of strict TRE period and the 9 months individually adjusted TRE period. EW, eating window; TRE, time‐restricted eating.

Adjustments in the eating window: The participants will be allowed to drink coffee and tea without milk/cream/sugar and other energy‐free beverages before the window opens (after wake‐up), and energy‐free and caffeine‐free beverages in the evening after the window closes (before bedtime). Participants can drink caffeine‐free coffee and teas like, for example, herbal tea, rooibos tea, fruit tea and chamomile tea in the evening.

Telephone calls: After 2, 6 and 9 weeks of intervention, participants will receive phone calls from health care professionals to provide support or guidance if needed.

Peer‐support group meetings: After 4 weeks of intervention, participants will be offered the possibility to meet with other participants at peer‐support group meetings at SDCC. The meetings will be facilitated by health care professionals and will be arranged as drop‐in sessions once monthly lasting for 1–1.5 h.

Involvement of relatives: Participants will be encouraged to involve relatives (family members or friends) in the intervention. They will be invited to bring their relatives to the trial visits and peer support group meetings. Further, they will receive a tool called ‘Our joint plan’ ³⁵ at the intervention start to help facilitate problem‐solving with relatives.

Nine months individually adjusted TRE

The strict period is followed by a 9‐month individually adjusted TRE period.

Conversation and adjustment of TRE

After 3 months of strict TRE, participants will return to SDCC for individual sessions about their TRE experiences. Based on these, participants will be offered adjustments and support options, including adjustments in their eating window and supplementary phone calls from health care professionals for support (Figure 2). Participants can also continue to make use of the adjustment and support options available from baseline (Figure 2).

4.6.2. Control group

The control group will follow standard care with regular visits at the SDCC or general practitioners 3–4 times/year. Participants will be instructed to continue their habitual lifestyle during the trial. Participants in the control group will not receive telephone calls from health care professionals during the study. After completing the trial, the control group will be offered an introduction to TRE (as described in Section 4.6.1).

4.7. Assessment of adherence

Twice weekly, participants in the TRE group will receive a text message with a link to an online questionnaire asking to report yesterday's eating window (using REDCap). The questionnaires will be sent to participants on random days, including weekdays and weekend days. Adherent days will be defined as participants reducing their eating window by at least 3 h compared to their habitual window and reporting an eating window of maximum 10 h. The habitual eating window will be measured during a 10‐day free‐living period between V0 and V1, from which an average habitual eating window will be calculated. Adherence to the intervention will be calculated as adherent days/total intervention duration X 100. Per protocol will be defined as ≥80% adherence. Participants in the TRE group will be offered paper diaries to voluntarily register daily eating windows, that is, start and stop time for intake of food and beverages as a tool to enhance adherence.

4.8. Trial visits

Figure 1 illustrates the six trial visits (see V0‐V5). On V1 (baseline), V3 (after 3 months) and V5 (after 1 year) test days, participants will arrive in the morning at SDCC ~9 am after a minimum of 12 h overnight fast. All participants will be instructed to have their last meal between 7 and 8 PM the day before to minimise the potential acute effect of varying fasting duration on the outcome of interest. ³⁶ Furthermore, no alcohol or strenuous physical activity will be allowed 48 h before V1, V3 and V5.

V2 (10 days before V3) and V4 (10 days before V5) visits will be short non‐fasting visits to initiate free‐living assessments including insertion of CGM, instruction to 4‐day dietary registrations and 10‐day registration of eating window.

A schematic overview of trial visits and process evaluation are displayed in Table 2, and descriptions of clinical assessments, questionnaires and process evaluation methods can be found in Supporting Information—Data S1.

4.9. Statistical methods

4.9.1. Sample size determination

The sample size was estimated based on a general linear model that is equivalent to a repeated measures mixed model with two timepoints (Proc GLMpower, SAS 9.4, SAS institute, NC, USA). A 5.5 mmol/mol (0.5%) difference in change was defined as the minimally important difference for the primary outcome, HbA_1c. The estimation was based on the following conditions/assumptions: an allocation ratio of 1:1, alpha = 0.025, beta = 0.1, a mean HbA_1c of 60 mmol/mol, ³⁷ , ³⁸ a standard deviation (SD) for HbA_1c at each timepoint of 13 mmol/mol ³⁷ , ³⁸ , ³⁹ , ⁴⁰ , ⁴¹ , ⁴² and a correlation between repeated measures of 0.8. ³⁷ This resulted in a total number of participants required to complete the trial of 114 for the ability to test the co‐primary endpoints; differences in HbA_1c changes from baseline to 3 months (hypothesis 1) and from baseline to 1 year (hypothesis 2). To account for potential uncertainties in the conditions used in the power calculation, the total number or participants was multiplied by 1.1 and then by 1.25 to account for potential dropouts, resulting in 160 participants to be included. However, in case it is not possible to recruit 160 participants due to practical reasons, we will only test HbA_1c changes from baseline to 1 year (hypothesis 2), which will increase alpha to 0.05, but otherwise with the same assumptions as described above; this will require 96*1.1*1.25 = 132 participants.

The RESET2 MRI sub‐study

The sample size was estimated from a previous study that evaluated cerebral insulin sensitivity as a change in cerebral blood flow in response to intranasal insulin before and after 8 weeks of Sodium‐Glucose Cotransporter‐2 treatment in individuals with prediabetes. ⁴³ The calculation was performed in R (version 4.2.2) with a power of 80% and type 1 error of 5%. Assuming a similar change in cerebral blood flow in response to intranasal insulin before and after the intervention of 8.89 mL/100 g/min and standard deviation of 8.68, ⁴³ a drop‐out rate of 10%, and a risk of missing data of 10%, 20 participants need to be included in each group.

4.9.2. Statistical analysis plan

Intention‐to‐treat analysis including all randomised participants will be performed after the last participant has completed the last visit. Furthermore, per protocol analysis will be performed including participants who are adherent during the TRE intervention. Descriptive statistics will be shown as mean (SD) for normally distributed data and as median (Q1; Q3) for non‐normally distributed data. Continuous variables, including the primary outcome, will be analysed using a baseline‐corrected linear mixed effects model. A full statistical analysis plan will be uploaded to ClinicalTrials.gov before the inclusion of participants is finalised.

4.10. Data management

All trial‐related information will be entered directly into electronic case report forms (eCRFs), pseudonymised by unique trial ID in the electronic data management system REDCap by the project staff (including health care professional) (version 13.7.14, Vanderbilt University, Tennessee, USA). The principles of Good Clinical Practice (GCP) will be followed in all data collection, records and completion of CRFs. For CGM measurements, liver scans, DXA scans and biometric measurements and food preferences, data will be registered on the device or related hardware, and uploaded to a secured logged drive which will only be accessible for project staff. Project staff and investigators will have access to the full dataset.

4.11. Ethics and dissemination

All equipment used in the trial will meet the requirement for patient safety and has previously been used in research projects. All adverse events will be recorded. Any unforeseen physical or psychological discomfort related to the intervention will be reported to the investigators.

The trial was approved by the Ethics Committee of Capital Region (H‐23035125) and registered at ClinicalTrials.gov (NCT06152588) before initiating the recruitment. The trial will be conducted following the Declaration of Helsinki. Possible protocol amendments will be approved by the Ethics Committee before coming into effect. The trial has been approved by the Capital Region of Denmark's Research Register (Privacy). The trial will be reported according to the Consolidated Standards of Reporting Trials (CONSORT). ⁴⁴ The trial protocol follows the Standard Protocol Items: Recommendations for Interventional Trials statement (SPIRIT). ⁴⁵

Positive, negative and inconclusive trial results will be published by the investigators in international peer‐reviewed journals, and all co‐authors will comply with the International Committee of Medical Journal Editors guidelines.

5. TRIAL STATUS

The first participant visit was on 19 April 2024. As of 29 December 2024, we have recruited 38 participants. We expect to recruit the last participant by December 2026.

6. STRENGTHS AND LIMITATIONS

The RESET2 trial, building on a comprehensive needs assessment and pilot study, is designed to include an individualised approach to TRE. This approach addresses potential barriers to adherence and long‐term sustainability. The 1‐year duration will allow for a thorough investigation of TRE's long‐term effects, feasibility and safety in individuals with type 2 diabetes, an underexplored topic. The interdisciplinary nature of the trial combines quantitative and qualitative methods to understand participants' experiences, strategies and support choices during the TRE intervention. Participants will vary within diabetes duration and degree of complications, introducing potential heterogeneity in trial outcomes and a broader generalisability of the study results.

AUTHOR CONTRIBUTIONS

JSQ and KF conceived the idea and JSQ, KF, ADT, AV, NB, GSH and NFH conceptualised and designed the trial. JSQ, KF and NFH obtained funding. All authors contributed to the design of the trial ADT wrote the first draft of the manuscript. All authors reviewed and edited the manuscript and approved the final version of the manuscript.

FUNDING INFORMATION

ADT, AV, NB, HZW, GSH, NJJ, FP, JIB, BE, DLH, KN, JR, LGG, MBB, NFH, KF and JSQ are employed at Steno Diabetes Center Copenhagen, a public hospital and research institution under the Capital Region of Denmark, which is partly funded by a grant from the Novo Nordisk Foundation. This RESET2 project was supported by funds from the Novo Nordisk Foundation (NNF200C0065836), the Danish Diabetes Academy which is funded by the Novo Nordisk Foundation (NNF17SA0031406) and the Danish Diabetes Association. The project funders were not involved in the design of the study; the collection, analysis and interpretation of data; writing the report and did not impose any restrictions regarding the publication of the report.

CONFLICT OF INTEREST STATEMENT

SDCC is a hospital providing health services for the public health care system. The research project and SDCC are funded by the Novo Nordisk Foundation through unrestricted grants. Thus, the Novo Nordisk Foundation has no economic interests in the study. The Novo Nordisk Foundation will not influence (1) the study design; (2) the collection, analysis and interpretation of data; (3) the writing of the study report or any publication and (4) the decision to submit the paper for publication. The investigators employed at SDCC will not benefit economically from conducting the study. SP is the author of the books The Circadian Code and The Circadian Diabetes Code, which advocate for time‐restricted eating. BE owns shares in Novo Nordisk A/S and has received speaker's fees from Novo Nordisk A/S. KN owns shares in Novo Nordisk; has been a paid consultant for Novo Nordisk and Medtronic; has received speaker honorarium and honorarium for Advisory Board to her institution from Medtronic, Novo Nordisk, Convatec and her institution has received research funding from Zealand Pharma, Novo Nordisk, Medtronic and Dexcom. LGG owns shares in Novo Nordisk A/S. KF is employed by Novo Nordisk A/S and owns shares in Novo Nordisk A/S. JSQ has received funding from Novo Nordisk A/S for other studies. AD, AM, NB, HZW, GSH, NJJ, FP, JIB, DLH, JR and MBB declare no conflict of interest.

Supporting information

Data S1: Supporting Information.

Termannsen A‐D, Varming A, Bjerre N, et al. Protocol for a 1‐year randomised, controlled, parallel group, open‐label trial on the effects and feasibility of time‐restricted eating in individuals with type 2 diabetes‐ The REStricted Eating Time in the treatment of type 2 diabetes (RESET2) trial. Diabet Med. 2025;42:e15506. doi: 10.1111/dme.15506

DATA AVAILABILITY STATEMENT

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.