Table 1.

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

	Location and time	Measurements
Pre-screening	Phone −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 months	Local 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.