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

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.

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

Study Overview

• Status: Not yet recruiting
• Conditions: Weight Loss Maintenance; Overweight or Obesity; Type 2 Diabetes
• Intervention / Treatment: Behavioral: AI assisted multi-domain lifestyle intervention; Drug: Tirzepatide

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.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Gang Liu, PHD; Phone Number: 86-15926238366; Email: liugang026@hust.edu.cn
• Study Contact Backup: Name: Zijun Tang; Phone Number: 86-13037181387; Email: tangzj_2024@163.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Tongji Medical College, Huazhong University of Science and Technology
      • Principal Investigator: Gang Liu
      • Contact: Gang Liu; Phone Number: 86-15926238366; Email: liugang026@hust.edu.cn
      • Principal Investigator: Tianshu Zeng

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. History of type 1 diabetes mellitus or other types of diabetes, or treatment with insulin.
2. History of obesity attributable to endocrine disorders or monogenic mutations.
3. A self-reported change in body weight ≥5.0% within 3 months prior to the day of screening.
4. Use of medications or products causing weight changes or affecting weight assessment within 3 months prior to the day of screening;
5. History of major adverse cardiovascular or cerebrovascular events within 6 months before screening (e.g., angina, myocardial infarction, arrhythmia, stroke, intracranial hemorrhage).
6. History of acute or chronic pancreatitis, pancreatic injury, or other high-risk factors for pancreatitis.
7. 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).
8. History of organ transplantation, congenital or acquired immunodeficiency disorders.
9. History of schizophrenia or major depressive disorder or other severe psychiatric disorders.
10. 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).
11. 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.
12. 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.

13. 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
14. 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.
15. 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).
16. Patients with active bacterial, viral, or fungal infections requiring hospitalization or antibiotic treatment.
17. History of infectious diseases such as human immunodeficiency virus (HIV), syphilis, or active hepatitis.
18. Female patients who are pregnant, lactating, or planning to become pregnant within the next two years.
19. Participation in other clinical trial within 3 months before screening or currently enrolled in other clinical trial study.
20. History of drug abuse or alcohol dependence within 6 months before screening.
21. Any other reasons that researchers deem to unsuitable for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AI assisted multi-domain lifestyle intervention; Participants will be randomized to receive multi-domain lifestyle intervention including diet, physical activity and psychological support for 52 weeks. Additionally, the weight loss maintenance program will integrate AI-assisted nutritional analysis to facilitate long-term weight management.	Behavioral: AI assisted multi-domain lifestyle intervention; AI-assisted multi-domain lifestyle interventions that integrate dietary, physical activity, and psychological components.
Active Comparator: Tirzepatide; Participants will be randomized to receive tirzepatide 5 mg treatment for 52 weeks.	Drug: Tirzepatide; Administered subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight change (kg)	Weight will be measured to the nearest 0.1 kg	Change from randomization (week 20) to week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in body weight	Percent change from week 20 to week 72	Change from randomization (week 20) to week 72
Body mass index	Weight / Height^2 (kg/m²)	Change from randomization (week 20) to week 72
Waist and hip circumference	Waist and hip circumference will be measured to the nearest 0.1cm	Change from randomization (week 20) to week 72
Body fat percentage	Change in body fat percentage (BF%) from randomization to the week 72	Change from randomization (week 20) to week 72
Skeletal muscle mass	Change in skeletal muscle mass (SMM) from randomization to the week 72, measured in kg	Change from randomization (week 20) to week 72
Fat mass	Change in fat mass (FM) from randomization to the week 72, measured in kg	Change from randomization (week 20) to week 72
Fat free mass	Change in fat free mass (FFM) from randomization to the week 72, measured in kg	Change from randomization (week 20) to week 72
Blood pressure	Blood pressure (systolic/diastolic) will be measured with a digital blood pressure monitor in sitting position (mmHg)	Change from randomization (week 20) to week 72
Concentration of glycated hemoglobin (HbA1c)	Concentration of HbA1c, measured in the percentage of hemoglobin	Change from randomization (week 20) to week 72
Concentration of fasting glucose	Concentration of fasting glucose, measured in mmol/L	Change from randomization (week 20) to week 72
Concentration of Insulin	Concentration of fasting insulin, measured in mU/L	Change from randomization (week 20) to week 72
Concentration of C-peptide	Concentration of fasting C-peptide, measured in mmol/L	Change from randomization (week 20) to week 72
Concentration of blood lipids	Concentration of blood lipids (total cholesterol, triglycerides, low-density lipoprotein cholesterol, high density lipoprotein cholesterol), measured in mmol/L	Change from randomization (week 20) to week 72
Body weight change (kg)	Weight will be measured to the nearest 0.1 kg	Change from baseline (week 0) to week 72
Percent change in body weight	Percent change from week 0 to week 72; Percentage of participants who achieve ≥5% body weight reduction; Percentage of participants who achieve ≥10% body weight reduction; Percentage of participants who achieve ≥15% body weight reduction	Change from baseline (week 0) to week 72
Waist and hip circumference	Waist and hip circumference will be measured to the nearest 0.1cm	Change from baseline (week 0) to week 72
Concentration of glycated hemoglobin (HbA1c)	Concentration of HbA1c, measured in the percentage of hemoglobin.	Change from baseline (week 0) to week 72
Concentration of blood lipids	Concentration of blood lipids (total cholesterol, triglycerides, low-density lipoprotein cholesterol, high density lipoprotein cholesterol), measured in mmol/L	Change from baseline (week 0) to week 72

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of high-sensitivity C-reactive protein (hs-CRP)	Concentration of hs-CRP, measured in mU/L	Change from baseline (week 0) to week 72
HOMA-IR	Fasting insulin (μU/mL) * fasting glucose (mmol/L) / 22.5	Change from baseline (week 0) to week 72
HOMA-β	20*Fasting insulin(μU/mL)／[fasting glucose (mmol／L)-3.5]	Change from baseline (week 0) to week 72
Visceral fat	MRI will be performed to measure liver and pancreatic fat	Change from baseline (week 0) to week 72
Liver stiffness measurement	Transient elastography will be performed to measure liver stiffness measurement (kPa).	Change from baseline (week 0) to week 72
Controlled attenuation parameter	Transient elastography will be performed to measure controlled attenuation parameter (dB/m)	Change from baseline (week 0) to week 72
Metagenomic analysis of the gut microbiota	The diversity of the gut microbiota will be assessed by whole-metagenomic sequencing	Change from baseline (week 0) to week 72
Liver function	Concentration of fasting Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT)	Change from baseline (week 0) to week 72
Concentration of serum creatinine	Concentration of serum creatinine, measured in μmol/L	Change from baseline (week 0) to week 72
Concentration of serum Cystatin C	Concentration of serum Cystatin C, measured in mg/L	Change from baseline (week 0) to week 72
Concentration of serum uric	Concentration of serum uric, measured in μmol/L	Change from baseline (week 0) to week 72
Estimated glomerular filtration rate	Estimated glomerular filtration rate (eGFR) was calculated using the MDRD equation, reported in mL/min/1.73 m²	Change from baseline (week 0) to week 72
Number of adverse events	N, frequency	Change from baseline (week 0) to week 72

Collaborators and Investigators

• Sponsor: Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: April 15, 2026
• First Submitted That Met QC Criteria: April 21, 2026
• First Posted (Actual): April 29, 2026

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Diabetes Mellitus, Type 2; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide
• Other Study ID Numbers: Lifestyle, Tirzepatide in T2D

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No