Type 2 DiabetesEDRSNCT07364045
Pancreas Lipotoxicity in T2D: Edinburgh Diabetes Remission Study (EDRS)
A study testing Total Diet Replacement (TDR) Program in people with Type 2 Diabetes, run by University of Edinburgh at 1 site in United Kingdom.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 45 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Total Diet Replacement (TDR) Program
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 15 Jun 2026to 31 Dec 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 79 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Clinical Research Facility, Royal Infirmary of Edinburgh
Edinburgh, EH16 4SA
Study Team, +44 131 242 6717, edrs@ed.ac.uk
About this study
Official title: 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).
Read more
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.
- Conditions
- Type 2 Diabetes
- Being tested
- Total Diet Replacement (TDR) Program
- Keywords
- Type 2 Diabetes, Obesity, Remission, Weight loss
- Medical subject headings
- Diabetes Mellitus, Type 2, Obesity, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Total Diet Replacement (TDR) ProgramBehavioural
Also called Low-Calorie Diet, Meal Replacement 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.
| Study group | Role | What they receive |
|---|---|---|
| Non-Diabetic Group | Experimental | 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. Receives: Behavioral: Total Diet Replacement (TDR) Program |
| Pre-Diabetic Group | Experimental | 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. Receives: Behavioral: Total Diet Replacement (TDR) Program |
| Short-Duration Type 2 Diabetes Group | Experimental | 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. Receives: Behavioral: Total Diet Replacement (TDR) Program |
| Long-Duration Type 2 Diabetes Group | Experimental | 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. Receives: Behavioral: Total Diet Replacement (TDR) Program |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in body weight from baseline to 6-12 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.
Measured: Baseline, 6 months, and 12 months post-intervention
Change in hepatic de novo lipogenesis measured using stable isotope tracers
Hepatic de novo lipogenesis will be quantified using stable isotope tracer methodology (deuterated water) at baseline and after intervention.
Measured: Baseline, 6 months, and 12 months
Secondary outcomes (8)
Change in liver and pancreas fat measured by MRI
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.
Measured: Baseline, 6 months, and 12 months
Change in beta-cell function assessed by C-peptide response during mixed meal test
Beta-cell function will be evaluated using C-peptide modeling during a standardised mixed meal test at baseline and after intervention.
Measured: Baseline, 6 months, and 12 months
Change in circulating lipoproteins and lipids
Lipoproteins (i.e. VLDL) and plasma/serum lipids will be measured using ultracentrifugation and mass spectrometry techniques.
Measured: Baseline, 6 months, and 12 months
Change in pancreas morphology and tissue inflammation
Pancreas size, shape, and tissue inflammation will be evaluated by assessed by MR methods at baseline and after intervention.
Measured: Baseline, 6 months, and 12 months
Change in adipose tissue biology
MRI will be used to assess fat saturation, and fat biopsies will be performed to evaluate molecular changes in adipose tissue biology.
Measured: Baseline and 6 months post-intervention
Change in circulating markers
Changes in circulating adipokines, inflammatory markers, and exosomes will be measured using commercial kits to assess systemic metabolic responses to weight loss.
Measured: Baseline and 6 months post-intervention
Change in lipid profile
Fasting lipids (TGs, HDL, LD cholesterol) will be measured at baseline and after intervention at NHS- accredited lab to assess cardiometabolic improvement.
Measured: Baseline, 6 months, and 12 months
Change in blood pressure
Blood pressure will be measured at baseline and after intervention to assess cardiometabolic improvement.
Measured: Baseline, 6 months, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2026
- Study start15 Jun 2026
- Primary completion30 Mar 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Participants are assigned to one of four parallel groups based on baseline glycemic status: non-diabetic, pre-diabetic, short-duration type 2 diabetes (\<6 years), and long-duration type 2 diabetes (\>10 years). All groups receive the same dietary intervention (8-12-week Total Diet Replacement followed by food reintroduction and weight maintenance), but remain in their respective groups for analysis. No crossover or sequential assignment occurs.
- Masking
- None (open label)
- Enrolment
- 104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Lothian
- Responsible party
- Sponsor
- Investigators
- Ahmad Al-Mrabeh, PhD, Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07364045
- Sponsor's protocol ID
- AC23027
- Acronym
- EDRS
- Status last verified
- Jun 2026
- First submitted
- 8 Jan 2026
- Last updated
- 18 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms Mediating Reversible Lipotoxicity of the Pancreas in Obesity-induced Type 2 Diabetes: Edinburgh Diabetes Remission Study (EDRS)
- ClinicalTrials.gov ID
- NCT07364045
- Acronym / sponsor ID
- EDRS / AC23027
- Conditions
- Type 2 Diabetes
- Keywords
- Type 2 Diabetes, Obesity, Remission, Weight loss
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 104 participants (estimated)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- NHS Lothian
- Study start
- 15 Jun 2026 (actual)
- Primary completion
- 30 Mar 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 23 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Participants are assigned to one of four parallel groups based on baseline glycemic status: non-diabetic, pre-diabetic, short-duration type 2 diabetes (<6 years), and long-duration type 2 diabetes (>10 years). All groups receive the same dietary intervention (8-12-week Total Diet Replacement followed by food reintroduction and weight maintenance), but remain in their respective groups for analysis. No crossover or sequential assignment occurs.
| Arm | Type | Receives |
|---|---|---|
| Non-Diabetic Group | Experimental | Behavioral: Total Diet Replacement (TDR) ProgramParticipants 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. |
| Pre-Diabetic Group | Experimental | Behavioral: Total Diet Replacement (TDR) ProgramParticipants 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. |
| Short-Duration Type 2 Diabetes Group | Experimental | Behavioral: Total Diet Replacement (TDR) ProgramParticipants 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. |
| Long-Duration Type 2 Diabetes Group | Experimental | Behavioral: Total Diet Replacement (TDR) ProgramParticipants 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. |
Who may qualify
- Ages
- 45 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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).
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Total Diet Replacement (TDR) ProgramAlso: Low-Calorie Diet, Meal Replacement ProgramParticipants 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. | Behavioural | Long-Duration Type 2 Diabetes Group, Non-Diabetic Group, Pre-Diabetic Group, Short-Duration Type 2 Diabetes Group |
Primary outcome
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.
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.
8 secondary outcomes
Change in liver and pancreas fat measured by MRI
Time frame: 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
Change in circulating lipoproteins and lipids
Time frame: Baseline, 6 months, and 12 months
Change in pancreas morphology and tissue inflammation
Time frame: Baseline, 6 months, and 12 months
Change in adipose tissue biology
Time frame: Baseline and 6 months post-intervention
Change in circulating markers
Time frame: Baseline and 6 months post-intervention
Change in lipid profile
Time frame: Baseline, 6 months, and 12 months
Change in blood pressure
Time frame: Baseline, 6 months, and 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ahmad Al-Mrabeh, PhD principal investigator
University of Edinburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Total Diet Replacement (TDR) Program in people with Type 2 Diabetes, run by University of Edinburgh at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Study Team (+44(0)131 242 6717, edrs@ed.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in body weight from baseline to 6-12 months post-intervention (time frame: Baseline, 6 months, and 12 months post-intervention). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2026.