Type2diabetesDepLivNCT06211556
Depletion of Liver Fat in Type 2 Diabetes
A study testing Very-low calorie diet in people with Type2diabetes and Obesity, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 30 to 70 years
- Conditions the study is for
- Type2diabetes, Obesity
- What is being tested?
- Very-low calorie diet
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Feb 2024to Mar 2026
- 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 30 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
- Diagnosis of Type 1 diabetes, MODY-diabetes, Type 1½ diabetes or LADA-diabetes
- 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)
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- Presence of metal in the body that would contraindicate an MRI scan
- 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
- Changes in hypothyroid disease treatment within the last 3 three months prior to enrolment
- 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
- Current treatment with anti-obesity medication
- Current treatment with anti-inflammatory medication
- Weight loss of > 5kg within the last 6 months
- 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)
- 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)
- Biochemical sign of other major diseases
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site, 1 recruiting
- Recruiting
Rigshospitalet - CFAS
Copenhagen, Capital Region, 2100
Inge Holm, +4535457621, inge.holm@regionh.dk
Cody G Durrer, PhD
About this study
Official title: 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).
Read the detailed description
Fibroblast growth factor 21 (FGF21) is a hepatokine that confers multiple beneficial effects when signaling to other tissues in the body. This is particularly true in adipose tissue, where it improves insulin sensitivity and leads to adiponectin production/secretion. In healthy individuals, FGF21 secretion is induced by exercise: however, this effect is absent in people living with type 2 diabetes (T2D). Aberrant secretion of FGF21 and other hepatokines is associated with increases in ectopic fat in the liver, but it is unknown if depletion of ectopic liver fat ameliorate this effect.
42 participants living with T2D will be recruited for this parallel randomized controlled trial. At baseline, participants will have their liver fat assessed via magnetic resonance imaging, exercise-induced FGF21 incremental area under the curve (following ~1 hour of exercise on a cycle ergometer at a workload equivalent to 60% VO2peak) as well as anthropometrics and outcomes relating to cardiometabolic health. Participants will then be randomized to either 1) two weeks of a very-low calorie diet (VLCD; ~800 kcal/day) or 2) two weeks of free living control (CON). Following the two week intervention period, participants will repeat the baseline outcome assessment.
The primary objective of this trial is to determine whether diet-induced liver fat depletion will restore exercise-induced FGF21 secretion in people living with T2D. Secondary objectives include determining the effect of diet-induced liver fat depletion on fasting levels of circulating FGF21 and expression of FGF21 receptor/co-receptors and downstream signals in adipose tissue, as well as other cardiometabolic outcomes.
- Conditions
- Type2diabetes, Obesity
- Being tested
- Very-low calorie diet
- Keywords
- VLCD, Exercise, Type 2 diabetes, hepatokines, Hepatic steatosis, Liver fat
- Medical subject headings
- Obesity, Motor Activity, Diabetes Mellitus, Type 2, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Very-low calorie dietBehavioural
Also called VLCD
~800 kcal/day delivered via commercially available diet plan (NUPO).
| Study group | Role | What they receive |
|---|---|---|
| Very-low calorie diet | Experimental | Two weeks of ~800kcal/day Receives: Behavioral: Very-low calorie diet |
| Free-living control | No intervention | No intervention control group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in change in FGF21 incremental area-under-the-curve
The difference in change between groups of FGF21 incremental area-under-the-curve in plasma following an exercise bout (continuous cycling at an intensity equivalent to 60% VO2peak for a gross energy expenditure of ~2500 kJ) from baseline to follow-up.
Measured: 4 weeks
Secondary outcomes (16)
Difference in change in fasting plasma FGF21
The difference in change between groups in fasting plasma FGF21 from baseline to follow-up.
Measured: 4 weeks
Difference in change in liver fat fraction
The difference in change between groups in liver fat fraction (assessed via MRI) from baseline to follow-up.
Measured: 4 weeks
Difference in change in fasting and post exercise plasma adiponectin
The difference in change between groups in fasting pre- and post-exercise adiponectin in plasma following an exercise bout from baseline to follow-up.
Measured: 4 weeks
Difference in change in adipose tissue mRNA targets relating to FGF21 signaling
Difference in change between groups in expression of the genes encoding adiponectin, FGFR1c, FGFR3c, and β-Klotho in subcutaneous adipose tissue from baseline to follow-up.
Measured: 4 weeks
Difference in change in fasting and post exercise plasma glucose
The difference in change between groups in fasting pre- and post-exercise glucose in plasma following an exercise bout from baseline to follow-up.
Measured: 4 weeks
Difference in change in fasting and post exercise plasma insulin
The difference in change between groups in fasting pre- and post-exercise insulin in plasma following an exercise bout from baseline to follow-up.
Measured: 4 weeks
Difference in change in fasting and post exercise plasma glucagon
The difference in change between groups in fasting pre- and post-exercise glucagon in plasma following an exercise bout from baseline to follow-up.
Measured: 4 weeks
Difference in change in the ratio of glucagon to insulin
The difference in change between groups in the fasting and post-exercise glucagon-to-insulin ratio in plasma from baseline to follow-up.
Measured: 4 weeks
Difference in change in fasting and post exercise plasma free fatty acids
The difference in change between groups in fasting pre- and post-exercise free fatty acids in plasma following an exercise bout from baseline to follow-up.
Measured: 4 weeks
Difference in change in HOMA indices
The difference in change between groups in homeostatic model assessment of insulin resistance and beta-cell function from baseline to follow-up.
Measured: 4 weeks
Difference in change in OGTT derived insulin sensitivity.
The difference in change between groups in OGTT derived insulin sensitivity (Matsuda index) from baseline to follow-up.
Measured: 4 weeks
Difference in change in OGTT derived insulin secretion.
The difference in change between groups in OGTT derived insulin secretion (area-under-the-curve for the ratio of insulin/glucose) from baseline to follow-up.
Measured: 4 weeks
Difference in change in OGTT derived beta-cell function
The difference in change between groups in OGTT derived beta cell function (disposition index calculated via the Matsuda index multiplied by the area-under-the-curve for the ratio of insulin/glucose) from baseline to follow-up.
Measured: 4 weeks
Difference in change in fasting plasma gamma-glutamyl transferase
The difference in change between groups in fasting levels of circulating gamma-glutamyl transferase (GGT) from baseline to follow-up.
Measured: 4 weeks
Difference in change in fasting plasma aspartate aminotransferase
The difference in change between groups in fasting levels of circulating aspartate aminotransferase (AST) from baseline to follow-up.
Measured: 4 weeks
Difference in change in fasting plasma alanine aminotransferase
The difference in change between groups in fasting levels of circulating alanine aminotransferase (ALT) from baseline to follow-up.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2024
- Study start1 Feb 2024
- Primary completionMar 2026 (estimated)
- Study completionMar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type2diabetesStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two arm open-label parallel group randomized controlled trial
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- Diabetesforeningen, Canadian Institutes of Health Research (CIHR), Region Hovedstadens Forskningsfond
- Responsible party
- Principal investigator, Cody Garett Durrer, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Cody G Durrer, Ph.D., Principal investigator, Center for Aktiv Sundhed - Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06211556
- Sponsor's protocol ID
- H-23045368
- Acronym
- DepLiv
- Status last verified
- Jul 2025
- First submitted
- 7 Dec 2023
- Last updated
- 22 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: If the data can be fully anonymized, the data can be shared.
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06211556
- Acronym / sponsor ID
- DepLiv / H-23045368
- Conditions
- Type2diabetes, Obesity
- Keywords
- VLCD, Exercise, Type 2 diabetes, hepatokines, Hepatic steatosis, Liver fat
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Collaborators
- Diabetesforeningen, Canadian Institutes of Health Research (CIHR), Region Hovedstadens Forskningsfond
- Study start
- 1 Feb 2024 (actual)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Mar 2026 (estimated)
- First posted
- 18 Jan 2024 (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.
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).
Detailed description
Fibroblast growth factor 21 (FGF21) is a hepatokine that confers multiple beneficial effects when signaling to other tissues in the body. This is particularly true in adipose tissue, where it improves insulin sensitivity and leads to adiponectin production/secretion. In healthy individuals, FGF21 secretion is induced by exercise: however, this effect is absent in people living with type 2 diabetes (T2D). Aberrant secretion of FGF21 and other hepatokines is associated with increases in ectopic fat in the liver, but it is unknown if depletion of ectopic liver fat ameliorate this effect.
42 participants living with T2D will be recruited for this parallel randomized controlled trial. At baseline, participants will have their liver fat assessed via magnetic resonance imaging, exercise-induced FGF21 incremental area under the curve (following ~1 hour of exercise on a cycle ergometer at a workload equivalent to 60% VO2peak) as well as anthropometrics and outcomes relating to cardiometabolic health. Participants will then be randomized to either 1) two weeks of a very-low calorie diet (VLCD; ~800 kcal/day) or 2) two weeks of free living control (CON). Following the two week intervention period, participants will repeat the baseline outcome assessment.
The primary objective of this trial is to determine whether diet-induced liver fat depletion will restore exercise-induced FGF21 secretion in people living with T2D. Secondary objectives include determining the effect of diet-induced liver fat depletion on fasting levels of circulating FGF21 and expression of FGF21 receptor/co-receptors and downstream signals in adipose tissue, as well as other cardiometabolic outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Two arm open-label parallel group randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| Very-low calorie diet | Experimental | Behavioral: Very-low calorie dietTwo weeks of ~800kcal/day |
| Free-living control | No intervention | –No intervention control group |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (35 listed)
- 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)
- Diagnosis of Type 1 diabetes, MODY-diabetes, Type 1½ diabetes or LADA-diabetes
- eGFR<60mL/min (assessed via screening blood sample)
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 |
|---|---|---|
| Very-low calorie dietAlso: VLCD~800 kcal/day delivered via commercially available diet plan (NUPO). | Behavioural | Very-low calorie diet |
Primary outcome
Difference in change in FGF21 incremental area-under-the-curve
Time frame: 4 weeks
The difference in change between groups of FGF21 incremental area-under-the-curve in plasma following an exercise bout (continuous cycling at an intensity equivalent to 60% VO2peak for a gross energy expenditure of ~2500 kJ) from baseline to follow-up.
16 secondary outcomes
Difference in change in fasting plasma FGF21
Time frame: 4 weeks
Difference in change in liver fat fraction
Time frame: 4 weeks
Difference in change in fasting and post exercise plasma adiponectin
Time frame: 4 weeks
Difference in change in adipose tissue mRNA targets relating to FGF21 signaling
Time frame: 4 weeks
Difference in change in fasting and post exercise plasma glucose
Time frame: 4 weeks
Difference in change in fasting and post exercise plasma insulin
Time frame: 4 weeks
Difference in change in fasting and post exercise plasma glucagon
Time frame: 4 weeks
Difference in change in the ratio of glucagon to insulin
Time frame: 4 weeks
Difference in change in fasting and post exercise plasma free fatty acids
Time frame: 4 weeks
Difference in change in HOMA indices
Time frame: 4 weeks
Difference in change in OGTT derived insulin sensitivity.
Time frame: 4 weeks
Difference in change in OGTT derived insulin secretion.
Time frame: 4 weeks
Difference in change in OGTT derived beta-cell function
Time frame: 4 weeks
Difference in change in fasting plasma gamma-glutamyl transferase
Time frame: 4 weeks
Difference in change in fasting plasma aspartate aminotransferase
Time frame: 4 weeks
Difference in change in fasting plasma alanine aminotransferase
Time frame: 4 weeks
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 22 Jul 2025.
- Individual participant dataSharing planned: No. If the data can be fully anonymized, the data can be shared.
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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.
Cody G Durrer, Ph.D. principal investigator
Center for Aktiv Sundhed - Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Very-low calorie diet in people with Type2diabetes and Obesity, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
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 6 inclusion and 35 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 22 Jul 2025. 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 Denmark. 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 Cody G Durrer, Ph.D. (+4550104538, cody.garett.durrer@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in change in FGF21 incremental area-under-the-curve (time frame: 4 weeks). 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 22 Jul 2025.