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NCT Number: NCT07364045

Pancreas Lipotoxicity in T2D: 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.

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Key information

Conditions

Type 2 Diabetes Body Weight Body Weight Changes Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms Weight Loss

Age range

45 year–79 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Clinical Research Facility, Royal Infirmary of Edinburgh

Edinburgh, EH16 4SA, United Kingdom

Location status: Recruiting

Location contact

Study Team

CONTACT

[email protected]

+44 131 242 6717

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Total Diet Replacement (TDR) Program

Behavioral

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

Primary outcomes

  1. 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.

  2. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Study Team

CONTACT

[email protected]

+44(0)131 242 6717

Sponsors and collaborators

Lead sponsor

University of Edinburgh

Other

Collaborators

  • NHS Lothian

Registry information

Official study title

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

Acronym: EDRS

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
Jan 23, 2026
Registry last updated
Jun 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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