A Feasibility Study of Optimal Non-Pharmacological Lifestyle Modifications in People With Type 2 Diabetes (ON LiMiT)

Steno Diabetes Centers

Status: Enrolling

Conditions: Type 2 Diabetes

Treatments: Other: CH-rich diet with exercise; Other: CH-reduced diet with exercise

Study type: Interventional

Funder types: Other

Identifiers

NCT07262788

1-10-72-77-25

Details and patient eligibility

About

The overall aim of this study is to examine the feasibility of a 12-month, two-arm lifestyle intervention to induce and maintain remission of type 2 diabetes (T2D). The findings from the feasibility study will inform the recruitment, design and delivery of the interventions in a 5-arm, 24-month randomised controlled trial.

Full description

Studies on T2D remission have reported varying rates of remission, often around 50% in intervention groups. These studies typically involve individuals with a recent T2D diagnosis, usually within six to ten years of diagnosis, with intervention periods most commonly lasting between twelve and twenty-four months, though durations have ranged from six to sixty months. Lifestyle interventions combining dietary changes and increased physical activity generally yield modest remission rates, but maintaining adherence over time remains challenging. Trials that include an initial phase of a very low-calorie diet, followed by ongoing structured support, tend to report higher remission rates. This emphasizes the critical role of significant and sustained weight loss. However, the most effective combination of dietary, exercise, and behavioral support strategies remains to be determined.

In addition to calorie restriction, changes in dietary composition may influence the underlying mechanisms of T2D. For instance, reducing carbohydrate intake can promote ketone production, affecting liver glucose production and improving glycemic control. Higher protein intake has been linked to an improved insulin response. Replacing saturated fats with polyunsaturated fats and increasing dietary fiber may also support glucose metabolism. However, it remains unclear whether carbohydrate-reduced or carbohydrate-rich diets are more effective in supporting long-term remission following initial weight loss.

Physical activity, particularly high-intensity exercise, plays a key role in reducing the risk of T2D, supporting weight management, and improving remission rates when combined with dietary interventions. Significant improvements in blood glucose control are usually seen with regular moderate-to-high-intensity exercise.

Moreover, there is considerable variation-or sometimes an absence-in the inclusion of key lifestyle intervention components, such as specific dietary and exercise protocols, as well as levels of supportive activities. This inconsistency complicates effective care provision for healthcare professionals and makes it difficult for individuals with T2D to adhere to non-pharmacological management recommendations.

Despite the known benefits of lifestyle modifications, initiating and maintaining these changes is challenging due to barriers such as a lack of support, motivation, and knowledge about nutrition and portion sizes. Involving individuals with T2D in designing and evaluating interventions may improve adherence, reduce participant burden, and increase the feasibility and scalability of lifestyle programs for wider implementation.

The overall aim of this study is to examine the feasibility of a 12-month, two-arm intervention designed to induce and maintain remission of T2D. After baseline measurements, participants will be randomized to one of two groups: Group A: Very-low-calorie-diet (VLCD)/weight loss followed by a carbohydrate-reduced (CH-reduced) diet combined with high-intensity exercise. Group B: VLCD/weight loss followed by a carbohydrate-rich (CH-rich) diet combined with high-intensity exercise. Participants will be blinded to the intervention arm during the VLCD phase. To determine the optimal macronutrient composition of the Mixed Meal Tolerance Test (MMTT) for subsequent testing, participants will attend three MMTTs in random order at baseline. The MMTTs consists of three different macronutrient compositions (X energy percentage (E%)carbohydrate, XE% protein, XE% fat; XE% carbohydrate, XE% protein, XE%fat; E% carbohydrate, XE% protein, XE% fat)

Feasibility will be evaluated based on the recruitment process, intervention acceptability, and participant adherence. This includes assessing whether the intervention components and outcome measurements are delivered and conducted as intended. Additionally, the study will examine how these elements perform in a real-life setting among individuals with T2D. Findings from this feasibility study will inform recruitment strategies, study design, and implementation of a subsequent five-arm, 24-month randomized controlled trial.

Specific aims:

1. To study the recruitment process (including recruitment of general practitioners and participants) and identify related barriers and facilitators.
2. To investigate retention, adherence, and acceptability of the interventions (carbohydrate-reduced or carbohydrate-rich diet combined with high-intensity exercise), including participant experiences with the intervention components and data collection procedures.
3. To assess whether the intervention is delivered as intended, covering supervised/unsupervised sessions, study visits, online support, and group education.
4. To evaluate the effectiveness of safety procedures in responding to changes in participants' glycemic control, blood pressure, physical injuries, and related risk markers.
5. To determine the optimal macronutrient composition and sampling schedule for the Mixed Meal Tolerance Test (MMTT).
6. To explore the potential impact of the two interventions on T2D remission rates and related metabolic outcomes such as body weight, body composition, blood pressure, vascular function, glycemic control, lipid profile, beta-cell function, and inflammation.

Enrollment: 24 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Building on previous findings from T2D remission studies involving VLCD interventions, the study include individuals with recently diagnosed T2D who are overweight or obese and not receiving insulin therapy. This subgroup has demonstrated the greatest benefit from significant weight loss. Participants using GLP-1 receptor agonists (GLP-1 RAs) are eligible, provided their weight has been stable for at least three months prior to inclusion. Individuals on insulin therapy will be excluded. Allowing GLP-1 RA use enhances the study's generalizability, as approximately 29% of people with T2D in Denmark are currently treated with these medications.

Inclusion Criteria:

• Diagnosis of T2D and treatment with lifestyle and/or oral anti-diabetic medication and/or glucagon-like peptide-1 receptor agonists (GLP-1RAs)
• HbA1c between 36-86 mmol/mol
• T2D duration of ≤6 years
• BMI ≥27 kg/m2
• Body weight changes over 3 months ≤3 kg

Exclusion Criteria:

• Insulin treatment within 6 months prior to screening (any type)
• Heart failure (ejection fraction<40%) and treated with SGLT-2i (current or planned)
• Kidney disease (eGFR<60 ml/min) and treated with SGLT-2i (current or planned)
• Physical comorbidity, which precludes the physical activity during intervention
• Dietary restrictions or allergies making the participant unable adhere to the dietary interventions
• Unable to comply with trial procedures and/or interventions
• Alcohol/drug abuse
• Planned or present pregnancy
• Unstable psychiatric disease
• Diagnosed with binge eating disorder
• Participation (present or planned) in other clinical trials including lifestyle or pharmacy trials for any condition
• If HbA1c ≥60 mmol/mol and the participant is on 2 or more anti-diabetic drugs a positive GAD65 and/or stimulated C-peptide <800 pM excludes the patient

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

CH-rich diet with exercise

Experimental group

Description:

A CH-rich diet combined with an exercise programme (n=12)

Treatment:

Other: CH-rich diet with exercise

CH-reduced diet with exercise

Experimental group

Description:

A CH-redcued diet combined with an exercise programme (n=12)

Treatment:

Other: CH-reduced diet with exercise