Safety and efficacy of intermittent fasting with or without exercise in people living with overweight or obesity and type 2 diabetes-The INTERFAST-3 study design

AIMS: Lifestyle modification, including caloric restriction and exercise, is fundamental in the treatment of people living with overweight and type 2 diabetes mellitus (T2D). The overall aim of lifestyle intervention schemes is to reduce body weight and improve glycaemic control to reduce the future risk of diabetes-associated complications. The aim of this study is to determine whether intermittent energy restriction, exercise or their combination is best suited for reaching these targets in individuals with T2D not treated with insulin. METHODS: This randomized, controlled, monocentric parallel-group trial is designed to investigate participants living with T2D, body mass index >27 kg/m², HbA1c ≥53 mmol/mol (≥7.0%) and ≤86 mmol/mol (≤10.0%) and without insulin therapy. Participants are equally and randomly allocated to one of four study groups: (1) intermittent energy restriction group, (2) exercise group, (3) combined intermittent energy restriction and exercise group and (4) control group. The intervention phase lasts 12 weeks, followed by a two-year follow-up phase. In addition to assessing body weight and glycaemic parameters, resting energy expenditure (REE) and body composition are measured. An oral glucose tolerance test is carried out at baseline and at the end of the intervention. Additionally, stool samples for microbiome analyses and individual-related outcomes are collected, and all participants are equipped with continuous glucose monitoring (CGM). The primary outcome measure is the change in bodyweight from baseline to day 84. TRIAL REGISTRATION: The study was registered at DRKS (Deutsches Register Klinischer Studien-German Clinical Trial Register DRKS-ID: DRKS00032036)-Date of registration: 11.10.2023.