Table 1.

Schedule of enrollment, interventions and assessments

	Enrollment	Allocation	Post-allocation						Close-out
Timepoint	− t1	0	K0	K1	K2	K3	K4	K5	tx
Enrolment
Eligibility screen	X
Informed consent	X
Clinical examination	X
Allocation		X
Intervention
Tirzepatide			Started with 2.5 mg with titration up to a maximum of 15 mg (weekly)
Placebo			Placebo injections (weekly)
Assessments
Clinical examination			X	X	X	X	X	X	X
Basic laboratory tests				X		X
Extended hormonal and laboratory investigations and continuous glucose monitoring			X						X
Measurement of body composition, bone mineral density, and muscle strength			X						X
Determination of shivering threshold and thermography			X						X
Measurement of brown adipose tissue quantity and activity using 18F-FDG-PET/CT			X						X
Measurement of brown adipose tissue quantity and liver steatosis using MRI			X						X
Resting energy expenditure measurement			X						X
Physical activity, heart rate and sleep monitoring			X						X
Continuous ketone monitoring					X		X
Subcutaneous WAT biopsies and analysis			X						X
Questionnaires			X						X

K0 refers to the first visit before the intervention, K1–5 refers to the visits after months 1 to 5 of intervention, Tx refers to the last visit after 24 weeks of intervention