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

Stanford University

Status and phase: Not yet enrolling; Phase 4

Conditions: Prediabetes / Type 2 Diabetes

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

Study type: Interventional

Funder types: Other

Identifiers

NCT06682351

76481

Details and patient eligibility

About

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

Enrollment: 200 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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200 participants in 3 patient groups

Mediterranean Diet/GLP1a/Metformin

Experimental group

Description:

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.

Treatment:

Dietary Supplement: MED

Drug: Metformin

Drug: GLP-1A

Metformin/Mediterranean Diet/GLP1a

Experimental group

Description:

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.

Treatment:

Dietary Supplement: MED

Drug: Metformin

Drug: GLP-1A

GLP1a/Metformin/Mediterranean Diet

Experimental group

Description:

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.

Treatment:

Dietary Supplement: MED

Drug: Metformin

Drug: GLP-1A