Home-based Intervention With Semaglutide Treatment Of Neuroleptica-Related Prediabetes

Absolute change in weight in kilogram

Height measured in meters at baseline and after 30 weeks.

weight (kg) and height (meters) will be combined to report body mass index in kg/m\^2 at baseline and after 30 weeks

Absolute change in waist circumference as measured in cm by the study nurse

Absolute change in insulin resistance as estimated by HOMA, using fasting serum levels of insulin (measured in pmol/Liter) and plasma glucose (measured in mmol/Liter). HOMA is calculated using the formula provided by Matthews et al., 1985 in Diabetologia

Blood sample with plasma triglyceride (reported in mmol/Liter)

Blood sample with cholesterol concentrations (reported in mmol/Liter)

Blood pressure is measured at home by study nurse while the participant is resting in a chair.

Cardiovascular risk markers: cardiovascular autonomic neuropathy (CAN) (Vagus TM®), and circulating levels of cardiovascular risk markers. CAN is considered a serious complication of diabetes, being associated with a 5-fold increased risk of CVD. Of interest to this study, CAN may be present prior to the development of diabetes and it can be improved by weight loss. As CAN may be measured by a hand held apparatus (Vagus TM®), measurements are easily performed in the homes of the enrolled patients. CAN will be measured at inclusion, at 15 weeks and at end of study. Results will not be covered in primary publication. The results will be included in a publication decribing cardiovascular risk in study population.

Pro-atherosclerotic changes: we want to perform a pilot study in a subsample of 20 participants from placebo vs. 20 participants from the Semaglutide group, focusing on pre-symptomatic atherosclerosis assessed by positron emission tomography/computed tomography (PET/CT) using 18F-sodium fluoride (NaF) as tracer. NaF-PET/CT is a novel way of detecting and measuring calcification in major arteries, potentially years or decades before manifest arterial wall calcification becomes detectable by cardiac CT. We plan to perform two NaFPET/CT acquisitions, i.e. at baseline and after 30 weeks treatment. Based on our experience, inclusion of 20 placebo- and 20 Semaglutide-treated subjects is suitable to perform the pilot study. We hypothesize a ≥10% decrease in global disease score as measured by NaF uptake in the heart and/or thoracic aorta, will be present after 30 weeks treatment. Will not be covered in primary publication. The results will be presented in a separate puplication.

Positive and Negative Symptom Scale 6 (PANSS-6): PANSS-6 is an operationalized rating of positive and negative symptoms, in people with schizophrenia, which is sensitive to change. PANSS-6 is a shorter version of the original 30-item version. It is validated and translated into Danish and has proven a good level of inter-rater reliability when rated based on the Simplified Negative and Positive Symptoms Interview (SNAPSI). PANSS-6 interview will be performed at baseline, and after 15 and 30 weeks. Minimum score: 6. Maximum score 42. Higher scores indicate more severe symptoms. These results will be presented in the primary publication.

Impact of Weight on Quality of Life-Lite (IWQOL-Lite): IWQOL-Lite is a reliable and valid self-report measure for assessing weight-related QoL in people with schizophrenia. It provides a total score plus scores on five domains (physical function, self-esteem, sexual life, public distress, and work). IWQOL-Lite will be measured at baseline, and after 15 and 30 weeks. It consist of 31 items with scores in multiple domains. The score is transformed into 0-100 scale (100 being best quality of life). Will not be covered in primary publication.

SF-36v2 is a well-researched, self-reported measure of health. It comprises 36 questions in 8 different domains. The survey will be applied in Danish, using the latest updated version 2 (SF-36v2). It will be measured at baseline, week 15 and week 30. Scoring of the health domain scales involves: (a) recoding item response values, (b) summing recoded response values for all items in a given scale to obtain the scale raw score, (c) transforming the scale raw score to a 0-100 score, (d) transforming the 0-100 score to a z score, and (e) transforming the scale z score to a T score (mean = 50, standard deviation = 10). In general, for individual respondents, T scores of 45 or greater indicate at least average overall functioning or well-being in the health domain or overall health dimension-physical or mental-being assessed, as compared to the U.S. general population. These results will be presented in the primary publication.

Medication Adherence Rating Scale (MARS): MARS is a validated and reliable measure of adherence for psychoactive medication. MARS constitutes 10 items rating the medical adherence. MARS will be measured at baseline, and at weeks 5, 9, 15, 19, 23, 28 and 30. Total scores range from 0 (low likelihood of medication adherence) to 10 (high likelihood). These data will not be presented in the primary publication.

The Simple Physical Activity Questionnaire (SIMPAQ): SIMPAQ has shown good test-retest reliability and has been validated against measures from Actigraph accelerometers. SIMPAQ will be measured at baseline, and at weeks 5, 9, 15, 19, 23, 28 and 30. The 5-item SIMPAQ required people being interviewed to account for time spent in bed overnight, time sedentary, including napping, time spent walking, time spent exercising and time engaged in incidental activity, averaged over the past seven-day period. The sum of the hours recorded in the five SIMPAQ boxes should add to approximately 24-h. Will not be covered in primary publication.

EQ-5D-3L is a widely applied instrument for the measurement and cost-benefit evaluation of health interventions. EQ-5D-3L will be measured at baseline, and at weeks 5, 9, 15, 19, 23, 28 and 30. EQ-5D-3L consists of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Within each dimension, there are three levels: no problems, some problems, and extreme problems. Patients are required to designate their health state by marking the box corresponding to the most relevant statement for each dimension. This choice yields a single-digit number representing the selected level for that dimension. These digits across the five dimensions can be assembled into a 5-digit number that characterizes the patient's overall health state. A total of 243 possible health states is defined in this way. A score of 11111 indicates the best health, while a score of 33333 reflects the poorest health. Will not be covered in primary publication.