AI-assisted Multi-domain Lifestyle Versus Tirzepatide for Weight Loss Maintenance in Adults With Type 2 Diabetes (AIM-MAINTAIN)

Official title

Effect of AI-assisted Multi-domain Lifestyle Intervention Versus Tirzepatide Treatment on Weight Loss Maintenance in Adults With Type 2 Diabetes: a Randomized Clinical Trial.

Overview

This is a randomized controlled trial to compare the effect of AI-assisted multi-domain lifestyle and continued tirzepatide on body weight loss maintenance. The study consists of two phases: a 20-week lead-in phase, during which all participants will receive weekly subcutaneous tirzepatide at the maximum tolerated dose (MTD), followed by a 52-week intervention phase. Participants who meet the randomization criteria after the lead-in phase will be randomly assigned to either AI-assisted multi-domain lifestyle intervention or tirzepatide 5 mg

Detailed description

Diabetes and obesity have emerged as critical public health problems in China. Notably, more than half of Chinese adults with diabetes are concurrently with overweight or obesity. Weight management is a cornerstone of type 2 diabetes treatment, with robust evidence showing that weight loss improves glycemic control, blood pressure, lipid profiles, and may facilitate diabetes remission. However, maintaining long-term weight loss remains a formidable clinical challenge. Current clinical guidelines recommend several maintenance strategies after achieving target weight loss, including continued use of anti-obesity medications (AOMs), dose reduction, or structured lifestyle interventions. Few studies have suggested that compared with continued tirzepatide treatment, switching to placebo resulted in significant weight regain. However, important knowledge gaps remain regarding the effectiveness of AI-assisted multi-domain lifestyle interventions that integrate dietary, physical activity, and psychological components compared with reduced dose of tirzepatide treatment on weight loss maintenance in patients with type 2 diabetes.

This study aims to investigate the effect of AI-assisted multi-domain lifestyle interventions on weight loss maintenance in overweight or obese patients with type 2 diabetes, compared with tirzepatide treatment.

Interventions

• Behavioral AI assisted multi-domain lifestyle intervention
  AI-assisted multi-domain lifestyle interventions that integrate dietary, physical activity, and psychological components.
• Drug Tirzepatide
  Administered subcutaneously.

Primary outcome measures

• Body weight change (kg) [Time frame: Change from randomization (week 20) to week 72]

Secondary outcome measures (12)

• Percent change in body weight [Time frame: Change from randomization (week 20) to week 72]
• Body mass index [Time frame: Change from randomization (week 20) to week 72]
• Waist and hip circumference [Time frame: Change from randomization (week 20) to week 72]
• Body fat percentage [Time frame: Change from randomization (week 20) to week 72]
• Skeletal muscle mass [Time frame: Change from randomization (week 20) to week 72]
• Fat mass [Time frame: Change from randomization (week 20) to week 72]
• Fat free mass [Time frame: Change from randomization (week 20) to week 72]
• Blood pressure [Time frame: Change from randomization (week 20) to week 72]
• Concentration of glycated hemoglobin (HbA1c) [Time frame: Change from randomization (week 20) to week 72]
• Concentration of fasting glucose [Time frame: Change from randomization (week 20) to week 72]
• Concentration of Insulin [Time frame: Change from randomization (week 20) to week 72]
• Concentration of C-peptide [Time frame: Change from randomization (week 20) to week 72]

Eligibility criteria

Inclusion criteria

• Male or female participants aged 18 to 65 years at the time of signing informed consent;
• Body Mass Index (BMI) ≥27.0 kg/m²;
• Type 2 diabetes mellitus diagnosed by physicians within the past 5 years prior to screening.
• Voluntary participation and provide written informed consent.

Exclusion criteria

• History of type 1 diabetes mellitus or other types of diabetes, or treatment with insulin.
• History of obesity attributable to endocrine disorders or monogenic mutations.
• A self-reported change in body weight ≥5.0% within 3 months prior to the day of screening.
• Use of medications or products causing weight changes or affecting weight assessment within 3 months prior to the day of screening;
• History of major adverse cardiovascular or cerebrovascular events within 6 months before screening (e.g., angina, myocardial infarction, arrhythmia, stroke, intracranial hemorrhage).
• History of acute or chronic pancreatitis, pancreatic injury, or other high-risk factors for pancreatitis.
• History of cancers (except for localized basal cell carcinoma, adenocarcinoma in situ of cervix or prostate carcinoma in situ); personal or family history of medullary thyroid carcinoma (MTC) or type 2 multiple endocrine neoplasia syndrome (MEN2), or history of thyroid nodules (category IV or higher).
• History of organ transplantation, congenital or acquired immunodeficiency disorders.
• History of schizophrenia or major depressive disorder or other severe psychiatric disorders.
• Poorly controlled hypertension at screening (systolic blood pressure (SBP) ≥160 mmHg and/or diastolic blood pressure (DBP) ≥100 mmHg despite at least 4 weeks of conventional antihypertensive therapy).
• History of clinically significant gastric emptying abnormalities, or history of severe chronic gastrointestinal disease, or history of diabetic gastroparesis, or long-term use of drugs that directly affect gastrointestinal motility, or history of gastrointestinal surgery.
• Those who are known to be allergic to any component of GLP-1 receptor agonists drugs, or have more than two allergies, or be allergic to soy, dairy, or similar foods.
• Laboratory evaluation at screening meet any of the following criteria:

• Calcitonin ≥50 pg/mL;
• Thyroid stimulating hormone (TSH) >6.0 or <0.4 mIU/L;
• Fasting C-peptide <0.81 ng/mL;
• Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) >2.5 × upper limit of normal (ULN) or total bilirubin (TBIL) >2.5 × ULN (except Gilbert's syndrome with conjugated bilirubin <35%);
• Triglycerides ≥5.7 mmol/L;
• Serum amylase >2.5 × ULN;
• eGFR <30 mL/min/1.73m²
• History of uncontrolled and potentially unstable proliferative retinopathy or maculopathy within 1 year prior to screening, or history of diabetic ketoacidosis, diabetic non-ketotic hyperosmolar coma, or severe metabolic disturbances with neurological and psychiatric disorders.
• History of clinically significant anemia, or epilepsy, or syncope or cardiac conditions (e.g. cardiac arrest, arrhythmias, atrioventricular block, structural heart disease, torsades de pointes).
• Patients with active bacterial, viral, or fungal infections requiring hospitalization or antibiotic treatment.
• History of infectious diseases such as human immunodeficiency virus (HIV), syphilis, or active hepatitis.
• Female patients who are pregnant, lactating, or planning to become pregnant within the next two years.
• Participation in other clinical trial within 3 months before screening or currently enrolled in other clinical trial study.
• History of drug abuse or alcohol dependence within 6 months before screening.
• Any other reasons that researchers deem to unsuitable for participation in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Tongji Medical College, Huazhong University of Science and Technology — Wuhan

Identifiers

NCT: NCT07555730 · Lifestyle, Tirzepatide in T2D

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗