Table 1

Study timeline of activities and measurements taken at each of the study events and visits

Location and timeMeasurements
Pre-screeningPhone
−35±10 days
  • Interview (by an experienced staff)

Local pathology
  • 75 g OGTT and HbA1c tests

Screening/enrolment
(non-fasting)
Clinical Research Facility
−30±15 days
  • Informed consent signed

  • Medical history, medications and medical examination

  • Blood (full blood count, liver and kidney function tests)

  • Height and weight (BMI calculated)

  • BIA (RMR)

  • Blood pressure

  • FreeStyle Libre Pro (to remove and send back after 14 days in a pre-paid envelope)

  • Smartphone app training

Home
  • Stool sample

  • Study entry questionnaire*

Baseline
(fasting)
Clinical Research Facility
0, treatment clock starts
  • Anthropometry

  • Blood pressure, pulse wave analysis

  • Blood (lipids)

  • Indirect calorimetry (REE, RQ)

  • DXA, FibroScan

  • Metformin 3 months’ supply with instructions and logbooks

  • Smartphone app training, according to study arm allocation

3 months
(fasting)
Clinical Research Facility
+90±10 days
  • Anthropometry

  • Blood pressure, pulse wave analysis

  • Blood (HbA1c)

  • Indirect calorimetry (REE, RQ)

  • FreeStyle Libre Pro (to remove and send back after 14 days in a pre-paid envelop)

  • Metformin 3 months’ supply with logbooks

  • Adverse events recording and monitoring

Home
  • Stool sample†

5.5 months
(non-fasting)
Clinical Research Facility
+166±10 days
  • FreeStyle Libre Pro and ActivePal

Local pathology
  • 75 g OGTT and HbA1c

6 months
(fasting)
Clinical Research Facility
+180±10 days
  • Anthropometry

  • Blood pressure, pulse wave analysis

  • Blood (lipids, HbA1c)

  • Indirect calorimetry (REE, RQ)

  • DXA, FibroScan

  • Metformin—unused pills collected and counted

  • Adverse events recording

Home
  • Stool sample†

  • Diet Satisfaction Questionnaire‡

12 monthsLocal pathology
  • HbA1c

Home
  • 12 months questionnaire§

  • *Questionnaire includes hunger/fullness, dietary habits and dislikes, physical activity, medications, dietary supplements, personal and family history of disease, food-frequency questionnaire.

  • †Gut microbiome features from stool samples collected at 3 and 6 months will be compared with baseline (exploratory outcome).

  • ‡The Laboratory for the Study of Human Ingestive Behavior, Pennsylvania State University are the copyright holders of the Diet Satisfaction Questionnaire.30

  • §Questionnaire includes diet (are you following the diet you were allocated to?), metformin (are you continuing the metformin treatment and dosage) and current body weight.

  • BIA, bioelectrical impedance analysis; BMI, body mass index; DXA, dual-energy X-ray absorptiometry; HbA1c, glycated haemoglobin; OGTT, oral glucose tolerance test; REE, resting energy expenditure; RMR, resting metabolic rate; RQ, respiratory quotient.