Heterogeneity of Diabetes: Integrated Muli-Omics to Identify Physiologic Subphenotypes and Evaluate Targeted Prevention

NCT06682351 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: 76481
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The study team will invite participants with prediabetes or mild diabetes (HbA1c 5.7-7.0) to join a 5-year research study that will define subphenotypes of type 2 diabetes based on underlying physiology (eg insulin resistance, beta-cell dysfunction, incretin defect, liver insulin resistance) and then test the hypothesis that response to three first-line treatments will vary according to metabolic subphenotype. Variables of interest include glucose, cardiovascular risk markers, and weight. Treatments include Mediterranean diet, metformin, and a GLP-1 agonist. Participants will go through an initial screening, followed by three treatment periods, each lasting 4 months with 3 month washout in-between treatment periods. This study will help us understand how personalized treatments can help control blood glucose, reduce cardiovascular risk, and manage weight. While there may be minor side effects-like slight discomfort from blood tests, gastrointestinal symptoms from some of the medications, and small radiation exposure from DXA body scans-the treatments offered in this study have all been well studied and are known to lower risk for diabetes and cardiovascular disease

Conditions

Prediabetes / Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Change in HbA1c

  The study team will compare the change in HbA1c levels from beginning to end of intervention to compare the efficacy of each treatment.

  At month 0, month 4, month 8, month 11, month 15, month 18

Secondary Outcomes (11)

• Change in Time in Range (TIR)

  At month 0, month 4, month 8, month 11, month 15, month 18

• Change in body weight

  At month 0, month 4, month 8, month 11, month 15, month 18

• Change in Blood Pressure

  At month 0, month 4, month 8, month 11, month 15, month 18

• Change in LDL Cholesterol

  At month 0, month 4, month 8, month 11, month 15, month 18

• Change in Triglycerides

  At month 0, month 4, month 8, month 11, month 15, month 18

Study Arms (3)

Mediterranean Diet/GLP1a/Metformin

EXPERIMENTAL

1. 16 weeks of following a Mediterranean diet: a mostly plant-based diet that includes vegetables, whole grains, whole fruits, legumes, nuts and seeds, with fish being the primary animal protein, and olive oil the primary fat. 2. 3 months washout 3. 16 weeks using GLP1 agonist: Dosing will be titrated per clinical guidelines and as per FDA approved clinical protocols. 4. 3 months washout 5. 16 weeks of using metformin: Dosing will initiate at 500mg TID and increased to 1000mg BID after one week.

Drug: Metformin; Drug: GLP-1A; Dietary Supplement: MED

Metformin/Mediterranean Diet/GLP1a

EXPERIMENTAL

1. 16 weeks of using metformin: Dosing will initiate at 500mg TID and increased to 1000mg BID after one week. 2. 3 months washout 3. 16 weeks of following a Mediterranean diet: a mostly plant-based diet that includes vegetables, whole grains, whole fruits, legumes, nuts and seeds, with fish being the primary animal protein, and olive oil the primary fat. 4. 3 months washout 5. 16 weeks using GLP1 agonist: Dosing will be titrated per clinical guidelines and as per FDA approved clinical protocols.

Drug: Metformin; Drug: GLP-1A; Dietary Supplement: MED

GLP1a/Metformin/Mediterranean Diet

EXPERIMENTAL

1. 16 weeks using GLP1 agonist: Dosing will be titrated per clinical guidelines and as per FDA approved clinical protocols. 2. 3 months washout 3. 16 weeks of using metformin: Dosing will initiate at 500mg TID and increased to 1000mg BID after one week. 4. 3 months washout 5. 16 weeks of following a Mediterranean diet: a mostly plant-based diet that includes vegetables, whole grains, whole fruits, legumes, nuts and seeds, with fish being the primary animal protein, and olive oil the primary fat.

Drug: Metformin; Drug: GLP-1A; Dietary Supplement: MED

Interventions

Metformin DRUG

16 weeks of using metformin: Dosing will initiate at 500mg TID and increased to 1000mg BID after one week.

Also known as: MET

GLP1a/Metformin/Mediterranean Diet; Mediterranean Diet/GLP1a/Metformin; Metformin/Mediterranean Diet/GLP1a

GLP-1A DRUG

16 weeks using GLP1a: Dosing will be titrated per clinical guidelines and as per FDA approved clinical protocols.

Also known as: Glucagon-like peptide-1 analog

GLP1a/Metformin/Mediterranean Diet; Mediterranean Diet/GLP1a/Metformin; Metformin/Mediterranean Diet/GLP1a

MED DIETARY_SUPPLEMENT

16 weeks of following a Mediterranean diet: a mostly plant-based diet that includes vegetables, whole grains, whole fruits, legumes, nuts and seeds, with fish being the primary animal protein, and olive oil the primary fat.

Also known as: Mediterranean Diet, energy-restricted Mediterranean diet

GLP1a/Metformin/Mediterranean Diet; Mediterranean Diet/GLP1a/Metformin; Metformin/Mediterranean Diet/GLP1a

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BMI ≥23 (≥22 in Asians) kg/m2 but \< 45 kg/m2
• HbA1c 5.7-8.0% while not on antihyperglycemic medications

You may not qualify if:

• Recent (\<6mos) CVD event
• active malignancy, kidney/liver disease pregnancy/lactation, chronic inflammatory disease, eating disorder, bariatric surgery
• history of acute pancreatitis
• family or personal history of medullary thyroid cancer
• current use of antihyperglycemic, diabetogenic, or weight loss medications (washout allowed if approved by primary physician)
• heavy alcohol use
• hct \<30, creatinine \> 1.4, ALT\> 3x ULN
• physical activity \>2 hours/day
• inability to come to Stanford CTRU for metabolic testing

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Prediabetic State; Diabetes Mellitus, Type 2

Interventions

Metformin; glucagon-like peptide 1 (7-36)amide; Glucagon-Like Peptide 1; Diet, Mediterranean

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Diet, Plant-Based; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Tracey McLaughlin, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alina Choi, BS

CONTACT

7144884516; linachoi@stanford.edu

Jasmine Yang, BA

CONTACT

jasminey@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine (Endocrinology)

Study Record Dates

• First Submitted: November 7, 2024
• First Posted: November 12, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)