The Effect of Diet or Medication to Lose Weight in People with Type 2 Diabetes and Liver Scarring

Phase 4

Recruiting

• Conditions: Diabetes Mellitus, Type 2; Liver Steatoses; Overweight or Obesity; Liver Fibrosis; Hepatic Steatosis; Hepatic Fibrosis
• Interventions: Other: early time restricted Mediterranean diet; Drug: Mysimba

• Registration Number: NCT06845345
• Lead Sponsor: Carmen Dietvorst

Brief Summary

In the Netherlands, there are many people with type 2 diabetes. More than half of these people also have fatty liver. This is a build-up of fat in the liver and can lead to long-term scarring and even death of the liver. Losing weight can help reduce this. Losing weight can be done with medication such as Mysimba®, which is often prescribed to people with type 2 diabetes, but losing weight can also be done with diet. In this study, the investigators want to combine a Mediterranean diet (with lots of vegetables, fruits, whole grain products, nuts and olive oil) with intermittent fasting. In addition participants are not allowed to eat after the evening meal. The investigators will compare this with a group of participants receiving Mysimba®, to see if a diet with intermittent fasting might be better for reducing fatty liver and liver scarring in people with type 2 diabetes.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-17
• Study First Submitted QC: 2025-02-24
• Last Update Submitted: 2025-02-24
• Study First Posted: 2025-02-25
• Last Update Posted: 2025-02-25
• Study Start: 2025-03
• Primary Completion: 2026-07
• Study Completion: 2027-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• Type 2 diabetes
• Moderate to severe liver fibrosis (LSM >8.0 kPa and <13.6 kPa)
• BMI > 27 kg/m2
• Aged 18-75 years
• Written informed consent

Exclusion Criteria

• An insufficient comprehension of the Dutch language (spoken and written)
• Female who is pregnant, breast-feeding or intends to become pregnant
• Participants with an established diagnosis of liver pathology like, but not limited to: Hepatitis B, Hepatitis C, Autoimmune hepatitis, Wilson's disease, Hemochromatosis, Primary biliary cholangitis, Primary sclerosing cholangitis, Alcoholic liver disease
• History of liver transplant, or current placement on a liver transplant list
• History of cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy or variceal bleeding
• Participants with active HIV infection and/or treatment
• Participants with diagnosed malignancies with or without active treatment
• Participants with history or pre-existing renal disease (eGFR <30 mL/min/1.73 m2)
• Participants with corticosteroid induced diabetes (while still using corticosteroids)
• Participants using GLP-1 agonists for less than 3 months or not yet on a stable dose
• Participants using MAO-inhibitors, opioids and/or methadone (due to contraindication)
• Known or suspected excessive alcohol consumption (>21 drinks/week for males or >14 drinks/week for females. One drink is equivalent to 10 grams of alcohol)
• Previous or planned (during the trial period) obesity treatment with surgery. However, previous interventions that, due to reversal or removal, do not have any influence on the patient's weight, in the opinion of the investigator, are allowed.
• Participants with a history or evidence of any other clinically significant condition or planned or expected procedure that in the opinion of the investigator, may compromise the patient's safety or ability to complete the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dietary arm	early time restricted Mediterranean diet	Calorie restricted Mediterranean diet, with an eating window between 8AM till 6PM (early time-restricted eating)
Pharmacological arm	Mysimba	32 mg/360 mg naltrexone/bupropion (Mysimba)

Primary Outcome Measures

Name	Time	Method
Between-group difference in liver fibrosis during six months	Change from baseline to 6 months	Measured as liver stiffness in kilopascals (kPa) by transient elastography with FibroScan. For a value between 0 and 8 kPa, no liver fibrosis is assumed. Anything above 8 kPa means liver fibrosis. The highest possible result is 75 kPa.

Secondary Outcome Measures

Name	Time	Method
Between group difference in liver steatosis during six months	Change from baseline to 6 months	Measured as Controlled Attenuation Parameter (CAP) score with FibroScan. This score will range from 100 to 400 decibels per meter (dB/m). A score below 238 dB/m means the amount of fatty change in the liver is not higher than normal.
Between-group difference in waist circumference during six months	Change from baseline to 6 months	Measured in centimeters (cm) with measuring tape. A healthy waist circumference for women is between 68 and 80 cm and for men between 79 and 94 cm.
Between-group difference in weight during six months	Change from baseline to 6 months	Measured in kilograms (kg) with Seca 888 compact digital flat scale. Along with height, BMI is calculated by dividing weight by height squared. BMI should be at least 27 kg/m\^2.
Between-group difference in height during six months	Change from baseline to 6 months	Measured in centimeters (cm) with a yardstick. Along with weight, BMI is calculated by dividing weight by height squared. BMI should be at least 27 kg/m\^2.
Between-group difference in body composition during six months	Change from baseline to 6 months	Impedance, resistance and reactance are measured in Ohm at 50 kHz with bioelectrical impedance analysis (Bodystat 500). The impedance measuring range is between 20 and 1300 Ohm.
Between-group difference in grip strength during six months	Change from baseline to 6 months	Measured in kilograms (kg) with a hand dynamometer (Jamar). The grip strength can be measured between 0 and 90 kg. Normal values depend on gender and age. In people aged 20-29, the average grip strength is 46 kg for men and 29 kg for women.
Between-group difference in glycaemic regulation during six months	Change from baseline to 6 months	Glycaemic regulation is determined from values measured in the blood. These include fasting blood glucose measured in millimoles per litre (mmol/l), haemoglobin A1c (HbA1c) measured in millimoles per mole (mmol/mol) and fasting insulin measured in milligrams per decilitre (mg/dl). Normal values are below 6.1 mmol/l for fasting glucose, below 53 mmol/mol for HbA1c and between 60-110 mg/dl for fasting insulin.
Between-group differences in cholesterol during six months	Change from baseline to 6 months	Total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides are measured in millimoles per litre (mmol/l) through blood samples. Normal values are \<5.0 mmol/l for total cholesterol, \<2.6 for LDL cholesterol, \>0.8 for HDL cholesterol and \<2.0 for triglycerides
Between-group differences in lipoproteins during six months	Change from baseline to 6 months	Apolipoprotein B (ApoB), apolipoprotein AI (ApoAI), lipoprotein a (Lp(a)) and Apolipoproteïne B48 are measured in grams per litre (g/l) through blood samples. Normal values are: ApoB 0.55-1.4 g/l for men and 0.55-1.25 g/l for women; ApoAI 1.1-2.05 g/l for men and 1.25-2.15 g/l for women; Lp(a) \<0.5 g/l. There are no normal values for Apolipoprotein B48 yet.
Between-group difference in blood pressure during six months	Change from baseline to 6 months	Systolic and diastolic blood pressure measured in millimetres of mercury pressure (mmHg). Normal values are 120-140 mmHg for systolic pressure and \<90 mmHg for diastolic pressure.
Between-group difference in liver enzymes during six months	Change from baseline to 6 months	Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are measured in units per litre (U/L). Normal values are \<50 U/L for men and \<35 U/L for women for ALT and \<40 U/L for men and \<32 U/L for women for AST.
Between-group difference in renal function during six months	Change from baseline to 6 months	Renal function is determined by measuring creatinine in micromol per litre (µmol/L) and eGFR in mL/min/1.73m\^2. Normal values are 62-106 µmol/L for men and 44-80 µmol/L for women for creatinine; \>90 mL/min/1.73m\^2 for eGFR.
Between-group difference in blood count during six months	Change from baseline to 6 months	Blood count is determined by thrombocytes and leukocytes in x10⁹/L. Normal values are 150-400 x10⁹/L for thrombocytes and 4.0-10.0 x10⁹/L for leukocytes.
Between-group difference in physical activity during six months	Change from baseline to 6 months	Physical activity will be measured with Activ8 Activity Tracker GEN2. Activity is measured in time (seconds), Metabolic equivalent (MET) and kilocalories (kcal). All for sitting, standing, walking, cycling, running and total/average. In addition, step count is also measured.
Between-group difference in lifestyle factors during six months	Change from baseline to 6 months	Food intake, demographic variables, drug use, smoking and drinking habits, (diabetes) medication use and compliance to the time restriction will be administered with a self-developed questionnaire
Between-group difference in quality of life during six months	Change from baseline to 6 months	Measured with SF-36 Questionnaire. This is a 36-item patient-reported questionnaire that covers eight health domains: physical functioning (10 items), bodily pain (2 items), role limitations due to physical health problems (4 items), role limitations due to personal or emotional problems (4 items), emotional well-being (5 items), social functioning (2 items), energy/fatigue (4 items), and general health perceptions (5 items). Scores for each domain range from 0 to 100, with a total higher score defining a more favorable health state.
Between-group difference in patient satisfaction during six months	Change from baseline to 6 months	Measured with Diabetes Treatment Satisfaction Questionnaire. It consists of 8 items, indicating how satisfied a person is with diabetes treatment. The score can be a minimum of 0 and a maximum of 36. The higher the score the more satisfied.

Trial Locations

Locations (1)

Franciscus; 🇳🇱 Rotterdam, Netherlands