Does a short course of rifaximin improve glycaemic control compared to standard therapy in patients with poorly controlled type 2 diabetes?

Study setting: Professorial Medical Unit, North Colombo Teaching Hospital, Ragama.

Participants will be requested to attend on an allocated day prior to lunch after due medications. They will be requested to bring a sample of stool in a provided stool culture bottle to be handed over. Stool samples will be stored at – 80 0 C for analysis by RNA sequencing of gut microbiota on a later date as the second phase of the study.

Participants will be randomized to intervention arm and control arm using simple randomization.Each patient will be subjected to a series of capillary glucose testing (prior to lunch, 1/2hr, 1 hour, and 2 hours after a standard lunch) and recorded as baseline values.

Intervention arm: patients will receive oral rifaximin 400 mg to be taken three times daily for two weeks along with standard of care.

Control arm: patients will receive standard management only.

Both groups will be subjected to standard diabetic management according to 2017 American Diabetic Association (ADA) guidelines. Advice regarding importance of drug compliance and diet control will be given to both groups.

At the end of two weeks and four weeks all participants will be requested to bring a stool sample which will be stored in – 80 0 C for future analysis. They will be subjected to the same series of capillary glucose testing after the same diet that was given during the previous occasion.

After three months, HbA1c will be performed in all the patients. If a significant difference in glycaemic control (either >1% reduction in HbA1c level or >10% reduction in PPBS in the rifaximin arm compared to control arm) at the end of statistical analysis is observed, the second phase of the study will be conducted.

Phase 2 All the patients registered in the first phase of the study will be registered for the second phase with their consent. In the second phase, stored stool samples will be analyzed using RNA sequencing technique to see the composition of gut microbiota identify correlates of the the difference in glycaemic control and restoration of gut microbiota.

1. Male and female patients aged between 18-80 years
2. Type 2 diabetes for more than 5 years with last HbA1c done within three months of recruitment of more than 8%

1. Patients with known allergies to rifaximin.
2. Patients who have taken any antibiotic within three months prior to the recruitment.
3. Patients who are on continuous proton pump inhibitors for more than one month duration at the time of recruitment
4. Patients who are on concurrent vitamin supplements at the time of recruitment.
5. Patients who have chronic lower gastro intestinal symptoms at the time of recruitment.
6. Patients who are pregnant or lactating