The goal of our site was to recruit 150 primarily Native American participants into GRADE. Participants will be recruited from the urban population in Phoenix mostly via the Phoenix Indian Medical Center. Potential volunteers will undergo screening examinations, followed by run-in period in which participants are titrated to maximal tolerated dose of metformin. At the completion of the run-in period, participants with hemoglobin A1Cs 6.8-8.5% will be eligible to continue in the study and be randomized to one of the additional medications noted above. Participants will undergo baseline and yearly oral glucose tolerance tests, neuropathy screens, cognitive testing, and health care questionnaires. Urine for albumin will be collected every 6 months. All participants will have their diabetes managed by GRADE staff. Participants whose hemoglobin A1Cs rise above 7.5% on repeated measurements will have their therapy intensified with the addition of insulin glargine or for those already on glargine with the rapid acting insulin aspart at meals. The recruitment began in June, 2013 and was completed in July 2017. We are currently following 144 randomized participants (142 randomized at our site and 2 who have transferred from other sites), the study will continue through 2021. This study has also included several important ancillary and sub-studies. We have participated in a study which investigates the role of auto-immunity in type 2 diabetes, and whether this affects response to treatment. We have also collected stool for gut microbiome measurements which will be analyzed for changes in gut microbiome in response to treatment and if these changes affect glycemia. We have also invited participants to wear a continuous glucose monitor (CGM) for 2 weeks to allow us to correlated average glucose to hemoglobin A1C in a racially and ethnically diverse cohort and to analyze how glucose variability is affected by treatment and whether it predicts longer term diabetes related outcomes.
