Liver Fat Reduction Through a Very-Low Calorie Diet in Type 2 Diabetes

Trial details

Who runs it

Copenhagen University Hospital, Rigshospitalet

Trial code

NCT06211556

Record updated

22 July 2025

Original description

The aim of this randomized trial is to determine whether liver fat depletion via a short-term (i.e., two weeks) very-low calorie diet will restore the normal exercise-induced secretion of a signaling protein (fibroblast growth factor 21) from the liver in people living with type 2 diabetes. Participants will have their liver fat, body composition, and various markers of metabolic health assessed and then will be randomized to either the very-low calorie diet intervention or a free-living control group for two weeks. Upon completion of the two-week intervention period, participants will redo all of the pre-intervention assessments. The changes in the assessments from before vs. after the intervention period will be compared between the two intervention groups (i.e., the very-low calorie diet group vs. the free living control group).Read full original descriptionShow less

A Parallel Group Randomized Trial Investigating the Effect of Hepatic Fat Depletion Via a Very-low Calorie Diet on Hepatokine Secretion and Function in People With Type 2 Diabetes

The aim of this randomized trial is to determine whether liver fat depletion via a short-term (i.e., two weeks) very-low calorie diet will restore the normal exercise-induced secretion of a signaling protein (fibroblast growth factor 21) from the liver in people living with type 2 diabetes. Participants will have their liver fat, body composition, and various markers of metabolic health assessed and then will be randomized to either the very-low calorie diet intervention or a free-living control group for two weeks. Upon completion of the two-week intervention period, participants will redo all of the pre-intervention assessments. The changes in the assessments from before vs. after the intervention period will be compared between the two intervention groups (i.e., the very-low calorie diet group vs. the free living control group).

Inclusion: Men and women 30-70 years of age; The target population is persons with type 2 diabetes. I.e., persons are eligible if they are diagnosed with type 2 diabetes either only with metformin for managing glucose or without use of glucose lowering medications. Persons with a HbA1c ≥ 48 mmol/mol with or without the use of glucose lowering medications are also eligible. Any glucose lowering medications other than metformin are disallowed (described under "Exclusion criteria, below); Diabetes duration < 7 years; Body Mass Index (BMI) ≥ 30 kg/m2 and ≤ 40 kg/m2; Accepts medical regulation by the study endocrinologist; Inactivity, defined as < 1,5 hours of structured physical activity pr. week at moderate intensity and cycling < 30 minutes/5 km pr. day at moderate intensity (moderate intensity = out of breath but able to speak).

Exclusion: Changes in hypothyroid disease treatment within the last 3 three months prior to enrolment; Current treatment with anti-obesity medication; Current treatment with anti-inflammatory medication; Changes in symptoms or anti-depressive medication three months prior to enrolment; Diagnosis of psychiatric disorder or treatment with anti-psychotic medication; History of suicidal behavior or ideations within the last three months prior enrolment; Previous surgical treatment for obesity (excluding liposuction > 1 year prior to enrolment); Diagnosis of Type 1 diabetes, MODY-diabetes, Type 1½ diabetes or LADA-diabetes; Known or signs of intermediate or severe microvascular complications to diabetes (retino-, neuro- or nephropathy); Known cancer; Lung disease, other than asthma that can be managed with beta2-agonists and does not exhibit seasonal variation; Known cardiovascular disease; Known hyperthyroid disease; Clinical or biochemical signs of hypothyroid disease; Known liver disease - defined as ALAT or ASAT elevated three times above upper limit; Known autoimmune disease; Psoriasis disease requiring systemic treatment or cutan elements bigger than a total area of 25 cm2; Other endocrine disorder causing obesity; Biochemical sign of other major diseases; HbA1c ≥ 75 mmol/mol with no glucose lowering medications; HbA1c ≥ 64 mmol/mol with mono glucose lowering therapy (if compliant with the prescription); HbA1c ≥ 57 mmol/mol with ≥ dual glucose lowering therapy (if compliant with the prescription); eGFR<60mL/min (assessed via screening blood sample); Treatment with any glucose-lowering medications other than metformin (e.g., insulin (long and/or short acting), sulphonylurea based drugs, glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, sodium-glucose co-transporter-2 inhibitors, thiazolidinediones, alpha-glucosidase inhibitors); Presence of metal in the body that would contraindicate an MRI scan; Weight loss of > 5kg within the last 6 months; Pregnant/considering pregnancy, or lactating; Functional impairments that prevent the performance of intensive exercise; Participation in other research intervention studies; Macroalbuminuria at pre-screening (assessed via screening blood sample); Presence of circulating glutamatdecarboxylase anti body (GAD) 65 (assessed via screening blood sample); Objective findings that contraindicate participation in intensive exercise; Incidental findings that contraindicate participation in the study; Unable to allocate the needed time to fulfill the intervention; Language barrier, mental incapacity, unwillingness, or inability to understand and be able to complete the interventions.

ClinicalTrials.gov NCT06211556