Stanford University
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
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 a…
16 weeks of using metformin: Dosing will initiate at 500mg TID and increased to 1000mg BID after one week.
16 weeks using GLP1a: Dosing will be titrated per clinical guidelines and as per FDA approved clinical protocols.
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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