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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mediterranean Diet/GLP1a/Metformin | Experimental |
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| Metformin/Mediterranean Diet/GLP1a | Experimental |
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| GLP1a/Metformin/Mediterranean Diet | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | Drug | 16 weeks of using metformin: Dosing will initiate at 500mg TID and increased to 1000mg BID after one week. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Time in Range (TIR) | Change in Time in Rage (TIR) as measured by continuous glucose monitor (CGM). TIR is defined as a range of 70-140 mg/dL. The study team will calculate the changes from beginning to end or each intervention and compare efficacy of each treatment in TIR. | At month 0, month 4, month 8, month 11, month 15, month 18 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Alina Choi, BS | Contact | 7144884516 | linachoi@stanford.edu | |
| Jasmine Yang, BA | Contact | jasminey@stanford.edu |
| Name | Affiliation | Role |
|---|---|---|
| Tracey McLaughlin, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University | Stanford | California | 94305 | United States |
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| ID | Term |
|---|---|
| D011236 | Prediabetic State |
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| C055453 | glucagon-like peptide 1 (7-36)amide |
| D052216 | Glucagon-Like Peptide 1 |
| D038441 | Diet, Mediterranean |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D004763 |
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| GLP-1A | Drug | 16 weeks using GLP1a: Dosing will be titrated per clinical guidelines and as per FDA approved clinical protocols. |
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| 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. |
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| Change in body weight | Compare efficacy of each treatment in change in body weight (kg). | At month 0, month 4, month 8, month 11, month 15, month 18 |
| Change in Blood Pressure | Compare efficacy of each treatment in change in blood pressure. | At month 0, month 4, month 8, month 11, month 15, month 18 |
| Change in LDL Cholesterol | Change in LDL cholesterol at the beginning and end of each intervention to compare the efficacy of each treatment. | At month 0, month 4, month 8, month 11, month 15, month 18 |
| Change in Triglycerides | Change in triglycerides at the beginning and end of each intervention period to compare the efficacy of each treatment. | At month 0, month 4, month 8, month 11, month 15, month 18 |
| Change in high-sensitivity C-reactive protein (hsCRP) | hsCRP will be measured at the beginning and end of each intervention period to compare the efficacy of each treatment. | At month 0, month 4, month 8, month 11, month 15, month 18 |
| Change in alanine transaminase (ALT) | ALT will be measured at the beginning and end of each intervention period to compare the efficacy of each treatment. | At month 0, month 4, month 8, month 11, month 15, month 18 |
| Change in adiponectin | Adiponectin will be measured at the beginning and end of each intervention period to compare the efficacy of each treatment. | At month 0, month 4, month 8, month 11, month 15, month 18 |
| HOMA-B | Change from baseline in HOMA-B at the beginning and end of each intervention period to compare the efficacy of each treatment. | At month 0, month 4, month 8, month 11, month 15, month 18 |
| HOMA-IR | Change from baseline in HOMA-IR at the beginning and end of each intervention period to compare the efficacy of each treatment. | At month 0, month 4, month 8, month 11, month 15, month 18 |
| Change in body fat mass | Body fat mass will be measured by dual-energy x-ray absorptiometry (DXA) scan at the beginning and end of each intervention period to compare the efficacy of each treatment. | At month 0, month 4, month 8, month 11, month 15, month 18 |
| D004700 | Endocrine System Diseases |
| Glucagon-Like Peptides |
| D052336 | Proglucagon |
| D005768 | Gastrointestinal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D000095500 | Diet, Plant-Based |
| D004035 | Diet Therapy |
| D044623 | Nutrition Therapy |
| D013812 | Therapeutics |
| D004032 | Diet |
| D009747 | Nutritional Physiological Phenomena |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |