Strategic Lifestyle Intervention for Metabolic Syndrome (SLIM-MET)

Summary

This study is a randomized, parallel-group, observer-masked clinical trial. A total of 200 obese participants with MetS will be enrolled. Eligible subjects will be randomly assigned to the ILI group or ULI group with an allocation ratio of 2:1. The ILI group will be instructed to eat in 8 hours while fasting in 16 hours on daily basis over 24 weeks. Furthermore, enhanced daily physical activities with walking more than 10,000 steps will be implemented. The enrolled participants will be instructed to follow a diet with reduction of daily intake of 500 kcals per day. ILI group will be asked to use the Health2Sync mobile app to track self-measured outcomes and daily diet control. The investigators objectively measure step counts for participants of ILI group during 24-week intervention period using a wearable device (Fitbit Inspire 2). Participants are asked to attach the pedometer on their waist belt, except while bathing and sleeping. The ULI group will be instructed to follow habitual meal timing. In addition, all participants of both groups will receive the health education. Anthropometric, sociodemographic data, biochemical variables, and metabolic variables will be measured at baseline and during follow-up visit. DEXA and MRI of abdomen will be measured at baseline and during following up visits. The proposed trial is designed to provide 85% statistical power to detect a significant difference in changes in the metabolic syndrome severity score after reduction \> 5% body weight over 24 weeks.

After completion of the initial 24-week lifestyle intervention, which often has limited weight loss efficacy when used alone, a second-phase intervention will be conducted from week 26 to week 52. Participants in both the ILI and ULI groups will be randomly assigned in a 1:1 ratio to receive one of two evidence-based oral weight control medications: a GLP-1 receptor agonist (Rybelsus) or an SGLT-2 inhibitor (Forxiga), for a duration of 26 weeks. The ILI group will continue with the daily 8-hour time-restricted eating and 16-hour fasting regimen, along with walking more than 10,000 steps per day. This phase aims to evaluate the effects of these two medications on weight reduction and liver fat content, with or without prior 26-week intensive lifestyle intervention. After the 26-week medication intervention, all participants will be followed for an additional 52 weeks to assess the sustainability of weight loss.

Conditions

• Metabolic Syndrome

Interventions

OTHER

Strategic lifestyle and drug interventions

Participants in the Intensive Lifestyle Intervention (ILI) group will follow a program including: 1. time-restricted eating with a 16:8 pattern (eating within an 8-hour window, fasting for 16 hours), 2. walking over 10,000 steps daily, and 3. a daily calorie reduction of 500 kcal (with macronutrient distribution: 40-55% carbohydrates, 15-20% protein, 20-30% fat). Participants in the Usual Lifestyle Intervention (ULI) group will maintain their habitual meal timing. After the initial 24-week lifestyle program, ILI participants will be randomized (1:1) to receive either a GLP-1 receptor agonist (Rybelsus) or an SGLT-2 inhibitor (Forxiga) for 26 weeks, while continuing their lifestyle regimen. This phase will assess the impact of medication-with or without prior lifestyle intervention-on weight loss and liver fat. All participants will then be followed for an additional 52 weeks to evaluate long-term weight maintenance.

OTHER

Control

Participants in the ULI group will maintain their usual lifestyle without intervention during the first 24 weeks. After the initial 24-week usual lifestyle intervention, participants in the ULI group will be randomly assigned in a 1:1 ratio to receive either Rybelsus (GLP-1 receptor agonist) or Forxiga (SGLT-2 inhibitor) for a duration of 26 weeks. This phase aims to assess the effects of these medications on weight reduction and liver fat content without prior intensive lifestyle intervention. All participants will be followed for an additional 52 weeks to evaluate the long-term sustainability of weight loss.

Sponsors & Collaborators

• Tri-Service General Hospital

  collaborator OTHER

• Chang Gung Memorial Hospital

  collaborator OTHER

• National Taiwan University Hospital Hsin-Chu Branch

  collaborator OTHER

• Taichung Armed Forces General Hospital

  collaborator OTHER_GOV

• National Health Research Institutes, Taiwan

  lead OTHER

Principal Investigators

• Wayne Huey-Herng Sheu, MD, PhD · National Health Research Institutes, Taiwan

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

20 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-03-14

Primary Completion

2027-10-10

Completion

2027-12-31

Countries

• Taiwan

Study Locations