Pancreas Lipotoxicity in T2D: Edinburgh Diabetes Remission Study (EDRS) (EDRS)

March 2, 2026 updated by: University of Edinburgh

Mechanisms Mediating Reversible Lipotoxicity of the Pancreas in Obesity-induced Type 2 Diabetes: Edinburgh Diabetes Remission Study (EDRS)

This study aims to investigate how fat accumulation in the pancreas contributes to the development of type 2 diabetes (T2D), and how weight loss may reverse this process. Previous research has shown that reducing body weight can lead to diabetes remission, and this was accompanied by lowering intrapancreatic fat and restoration of insulin secretion, but the mechanisms behind this are not fully understood. In particular, the study aims to unravel the role of hepatic de novo lipogenesis (DNL) and lipoprotein metabolism on pancreas lipotoxicity and beta cell recovery after weight loss.

Four groups of participants will be recruited (n=26 per group): non-diabetic, pre-diabetic, short-duration T2D (<6 years), and long-duration T2D (>10 years). Participants will be aged between 45 and 79 years and have a BMI between 30 and 45 kg/m². All participants will follow a structured weight loss programme using an 800 kcal/day Total Diet Replacement (TDR) for 8-12 weeks, followed by dietary support to maintain weight loss. The study is sponsored by NHS-Lothian and the University of Edinburgh and will be carried out at the Clinical Research Facility, Royal infirmary of Edinburgh by a specialist team (Senior Diabetes Research Nurse, Clinical Fellow, and Research Dietitian).

The primary endpoint of this study is to achieve a 10-15% reduction in body weight (~10 kg) through a low-calorie diet (800 kcal/day) to induce T2D remission and maintain this weight loss with structured dietary support for up to 6-12 months. The primary aim is to compare hepatic de novo lipogenesis-the conversion of sugar into fat by the liver-and lipoprotein export among the groups, and to examine how these parameters change in response to weight loss, improvement in metabolic status, and restoration of normal pancreatic function.

Secondary endpoints include changes in weight, HbA1c, intraorgan fat (liver/pancreas), pancreas volume and tissue characteristics, beta cell mass and function (MRI/mixed meal test), circulating blood markers (i.e. lipids, exosomes, adipokines, and inflammatory markers), and the change in adipose tissue biology (fat biopsies).

Ultimately, this study aims to understand the mechanisms of T2D remission. It will help clarify the sequence of metabolic events leading to reversible pancreatic lipotoxicity and may inform the development of new, targeted therapies for T2D.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
104

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Study Team
  • Phone Number: +44(0)131 242 6717
  • Email: edrs@ed.ac.uk

Study Locations

  • United Kingdom
      • Edinburgh, United Kingdom, EH16 4SA
        • Recruiting
        • Clinical Research Facility, Royal Infirmary of Edinburgh
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Overweight/obese (BMI: 30-45 kg/m²) who have had T2D for less than 6 years or longer than 10 years, and are on treatment with diet alone or diet plus oral medication.
  • Overweight/obese (BMI: 30-45 kg/m²) who are at pre-diabetes stage, defined as fasting blood glucose 5.6-6.9 mmol/L.
  • Overweight/obese (BMI: 30-45 kg/m²) who are non-diabetic (control group).
  • Age between 45 and 79 years inclusive.
  • Post-menopausal women only (to exclude sex hormone effects on lipid metabolism).
  • Good communication in English (able to give informed consent and follow dietary advice).
  • Willing and able to adhere to the study protocol, including dietary intervention and scheduled follow-up visits.

Exclusion Criteria:

  • Insulin therapy
  • HbA1c >12% (108 mmol/mol)
  • Weight loss >5 kg in last 6 months
  • Recent MI (within 6 months)
  • Known cancer in last 5 years
  • First-degree relatives of people with T2D (control group)
  • History of gestational diabetes
  • MRI contraindications (metal implants, claustrophobia)
  • Alcohol >14 units/week
  • Advanced kidney or liver disease
  • Use of steroids or antipsychotics
  • Participation in another clinical trial
  • Life expectancy <1 year
  • Allergy to local anaesthetic (for biopsy subgroup)
  • Any disorder that may jeopardise safety or compliance

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Non-Diabetic Group
Participants without diabetes who are overweight or obese (BMI 30-45 kg/m²) will undergo an 8-12-week Total Diet Replacement (TDR) intervention (~800 kcal/day) followed by food reintroduction and weight maintenance. Includes metabolic testing, MRI scans, and blood sampling at baseline and follow-up.
Behavioral: Total Diet Replacement (TDR) Program
Participants will follow a structured Total Diet Replacement (TDR) program consisting of approximately 800 kcal/day using commercially available soups and shakes for 8-12 weeks. This is followed by a 2-week food reintroduction phase and a weight maintenance phase up to 6 months, supervised by a research dietitian. The intervention aims to induce rapid weight loss and assess its impact on intrapancreatic fat, insulin secretion, and type 2 diabetes remission. All participants receive dietary counseling and monitoring throughout the study.
Other Names:
  • Low-Calorie Diet
  • Meal Replacement Program
Experimental: Pre-Diabetic Group
Participants with pre-diabetes who are overweight or obese (BMI 30-45 kg/m²) will receive the same TDR intervention and follow-up schedule as the Non-Diabetic Group, with additional oral glucose tolerance testing during screening.
Behavioral: Total Diet Replacement (TDR) Program
Participants will follow a structured Total Diet Replacement (TDR) program consisting of approximately 800 kcal/day using commercially available soups and shakes for 8-12 weeks. This is followed by a 2-week food reintroduction phase and a weight maintenance phase up to 6 months, supervised by a research dietitian. The intervention aims to induce rapid weight loss and assess its impact on intrapancreatic fat, insulin secretion, and type 2 diabetes remission. All participants receive dietary counseling and monitoring throughout the study.
Other Names:
  • Low-Calorie Diet
  • Meal Replacement Program
Experimental: Short-Duration Type 2 Diabetes Group
Participants with type 2 diabetes diagnosed <6 years who are overweight or obese (BMI 30-45 kg/m²) will undergo the TDR intervention and extended follow-up (up to 12-24 months) with additional metabolic visits and blood sampling.
Behavioral: Total Diet Replacement (TDR) Program
Participants will follow a structured Total Diet Replacement (TDR) program consisting of approximately 800 kcal/day using commercially available soups and shakes for 8-12 weeks. This is followed by a 2-week food reintroduction phase and a weight maintenance phase up to 6 months, supervised by a research dietitian. The intervention aims to induce rapid weight loss and assess its impact on intrapancreatic fat, insulin secretion, and type 2 diabetes remission. All participants receive dietary counseling and monitoring throughout the study.
Other Names:
  • Low-Calorie Diet
  • Meal Replacement Program
Experimental: Long-Duration Type 2 Diabetes Group
Participants with type 2 diabetes diagnosed >10 years who are overweight or obese (BMI 30-45 kg/m²) will receive the same TDR intervention and standard follow-up schedule as other arms.
Behavioral: Total Diet Replacement (TDR) Program
Participants will follow a structured Total Diet Replacement (TDR) program consisting of approximately 800 kcal/day using commercially available soups and shakes for 8-12 weeks. This is followed by a 2-week food reintroduction phase and a weight maintenance phase up to 6 months, supervised by a research dietitian. The intervention aims to induce rapid weight loss and assess its impact on intrapancreatic fat, insulin secretion, and type 2 diabetes remission. All participants receive dietary counseling and monitoring throughout the study.
Other Names:
  • Low-Calorie Diet
  • Meal Replacement Program

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in body weight from baseline to 6-12 months post-intervention
Time Frame: Baseline, 6 months, and 12 months post-intervention
The primary endpoint is achieving a 10-15% reduction in body weight (~10 kg) through a low-calorie diet (800 kcal/day) to induce T2D remission and maintain this weight loss with structured dietary support for up to 6-12 months. The study will also compare four participant groups (non-diabetic, pre-diabetic, short-duration T2D, long-duration T2D) in terms of hepatic de novo lipogenesis and lipoprotein export, and examine changes in these parameters in response to weight loss and improved metabolic status.
Baseline, 6 months, and 12 months post-intervention
Change in hepatic de novo lipogenesis measured using stable isotope tracers
Time Frame: Baseline, 6 months, and 12 months
Hepatic de novo lipogenesis will be quantified using stable isotope tracer methodology (deuterated water) at baseline and after intervention.
Baseline, 6 months, and 12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in liver and pancreas fat measured by MRI
Time Frame: Baseline, 6 months, and 12 months
Hepatic and intrapancreatic fat will be assessed by MRI at baseline and after intervention to evaluate the effect of weight loss on intraorgan fat deposition.
Baseline, 6 months, and 12 months
Change in beta-cell function assessed by C-peptide response during mixed meal test
Time Frame: Baseline, 6 months, and 12 months
Beta-cell function will be evaluated using C-peptide modeling during a standardised mixed meal test at baseline and after intervention.
Baseline, 6 months, and 12 months
Change in circulating lipoproteins and lipids
Time Frame: Baseline, 6 months, and 12 months
Lipoproteins (i.e. VLDL) and plasma/serum lipids will be measured using ultracentrifugation and mass spectrometry techniques.
Baseline, 6 months, and 12 months
Change in pancreas morphology and tissue inflammation
Time Frame: Baseline, 6 months, and 12 months
Pancreas size, shape, and tissue inflammation will be evaluated by assessed by MR methods at baseline and after intervention.
Baseline, 6 months, and 12 months
Change in adipose tissue biology
Time Frame: Baseline and 6 months post-intervention
MRI will be used to assess fat saturation, and fat biopsies will be performed to evaluate molecular changes in adipose tissue biology.
Baseline and 6 months post-intervention
Change in circulating markers
Time Frame: Baseline and 6 months post-intervention
Changes in circulating adipokines, inflammatory markers, and exosomes will be measured using commercial kits to assess systemic metabolic responses to weight loss.
Baseline and 6 months post-intervention
Change in lipid profile
Time Frame: Baseline, 6 months, and 12 months
Fasting lipids (TGs, HDL, LD cholesterol) will be measured at baseline and after intervention at NHS- accredited lab to assess cardiometabolic improvement.
Baseline, 6 months, and 12 months
Change in blood pressure
Time Frame: Baseline, 6 months, and 12 months
Blood pressure will be measured at baseline and after intervention to assess cardiometabolic improvement.
Baseline, 6 months, and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Edinburgh

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
NHS Lothian

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ahmad Al-Mrabeh, PhD, University of Edinburgh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 30, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 30, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 8, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 16, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 23, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 4, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 2, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AC23027

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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