Trial Outcomes & Findings for Research Study of How Well Semaglutide Works in People Living With Overweight or Obesity. (NCT NCT04251156)

The trial was conducted at 28 sites in 3 countries as follows (all sites screened and randomized): Region China (includes China mainland and Hong Kong) China mainland (23 sites) and Hong Kong (1 site), Brazil (2 sites) and South Korea (2 sites).

Participants were randomized in 2:1 ratio to receive 2.4 mg semaglutide subcutaneously (s.c.) or semaglutide matching placebo. The trial has a 44-week treatment period (16 weeks of dose escalation period and 28 weeks of maintenance period), followed by a 7-week follow-up period.

Research Study of How Well Semaglutide Works in People Living With Overweight or Obesity.

Change from baseline at week 0 to week 44 in body weight (%) is presented.The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Number of participants who achieved \>=5% weight reduction at week 44 for in-trial observation period is presented.In the reported data, 'Yes' infers the number of participants who have achieved greater than or equal to 5% weight reduction, whereas 'No' infers the number of participants who have not achieved greater than or equal to 5% weight reduction. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Number of participants who achieved \>=10% weight reduction at week 44 for in-trial observation period is presented. In the reported data, 'Yes' infers the number of participants who have achieved greater than or equal to 10% weight reduction, whereas 'No' infers the number of participants who have not achieved greater than or equal to 10% weight reduction. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Number of participants who achieved \>=15% weight reduction at week 44 for in-trial observation period is presented. In the reported data, 'Yes' infers the number of participants who have achieved greater than or equal to 15% weight reduction, whereas 'No' infers the number of participants who have not achieved greater than or equal to 15% weight reduction. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change in waist circumference from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change in body weight from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change in BMI from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Number of participants who achieved \>=20% weight reduction at week 44 for in-trial observation period is presented. In the reported data, 'Yes' infers the number of participants who have achieved greater than or equal to 20% weight reduction, whereas 'No' infers the number of participants who have not achieved greater than or equal to 20% weight reduction. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change in systolic blood pressure from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

SF-36 is a 36-item participants-reported survey of participants health that measures the partici-pants overall health-related quality of life (HRQoL). SF-36 questionnaire measured 8 domains of functional health and well-being as well as 2 component summary scores (physical component summary and mental component summary). This outcome measure shows results for 'physical functioning domain'. Physical function domain score ranges from 0 to 100, with higher values indicating better functional health and well-being. Change from baseline (week 0) in the domain scores were evaluated at week 44. These outcome measures were evaluated based on data from in-trial observation period which is the uninterrupted time interval from (week 0) to (week 51).

The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on participants quality of life within the context of clinical trials. IWQOL-Lite-CT is a 20-item questionnaire-based instrument used to assess the impact of body weight changes on participants overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite and physical function domain scores range from 0 to 100, with higher scores reflecting better levels of functioning. This outcome measure shows results for 'physical function domain'. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change in glycosylated haemoglobin (HbA1c) (%) from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change in HbA1c (mmol/mol) from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change in fasting plasma glucose (mg/dL) from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change in FPG (mmol/L) from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change in fasting serum insulin measured as milli-international units per milliliter (mIU/mL) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change in diastolic blood pressure from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change in total cholesterol measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change in HDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change in LDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change in VLDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change in free fatty acids measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change in triglycerides measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

SF-36 is a 36-item participant-reported survey of health that measures the overall HRQoL. SF-36 questionnaire measured 8 domains of functional health and well-being as well as 2 component summary scores (physical and mental component summary). This outcome measure shows results for all domains (except physical functioning) and 2 component summary scores. The score ranges from 0 to 100, with higher values indicating better functional health and well-being. Change from baseline week 0 in domain and component summary scores were evaluated at week 44 based on data from in-trial observation period which is uninterrupted time interval from (week 0) to (week 51).

The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on participants quality of life within the context of clinical trials. IWQOL-Lite-CT is a 20-item questionnaire-based instrument used to assess the impact of body weight changes on participants overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite scores for physical domain score, psychosocial domain score and total score ranges from 0 to 100, with higher scores reflecting better levels of functioning. This outcome measure shows results for 'physical and psychosocial domains, and for total'. The outcome measure was evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of randomization (week 0) to last trial-related participant-site contact (week 51).

The number of participants experiencing a meaningful within participant improvement in SF-36 Physical function after 44 weeks was determined based on 3.7 threshold. The threshold of 3.7 is specific for overweight or obese population included in the study and calculated using participant global rating anchor questionnaires to reflect participants own perspective based on Food and Drug Administration (FDA) recommendations. In the reported data, "Yes" infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and "No" infers number of participants who have not achieved an improvement in score greater than or equal to the threshold. The outcome measure was evaluated based on in-trial observation period which is the uninterrupted time interval from start of randomization (week 0) to last trial-related participant-site contact (week 51).

The number of participants experiencing a meaningful within participant improvement in IWQOL-Lite-CT physical function after 44 weeks was determined based on thresholds of 14.6. The threshold of 14.6 is specific for the population with overweight or obesity included in the study and calculated using patient global rating anchor questionnaires to reflect participants own perspective based on FDA recommendations. In the reported data, "Yes" infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and "No" infers the number of participants who have not achieved an improvement in score greater than or equal to the threshold. The outcome measure was evaluated based on in-trial observation period which is the uninterrupted time interval from start of randomization (week 0) to last trial-related participant-site contact (week 51).

Number of participants with T2D who achieved HbA1c \< 7% (53 mmol/mol) at week 44 is presented. In the reported data, "Yes" infers the number of participants who have achieved HbA1c values less than the 7% and "No" infers the number of participants who have not achieved HbA1c values less than the 7%. The outcome measure was evaluated based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Number of participants with T2D who achieved HbA1c \<= 6.5% (48 mmol/mol) at week 44 is presented. In the reported data, "Yes" infers the number of participants who have achieved HbA1c values less than or equal to 6.5% and "No" infers the number of participants who have not achieved HbA1c values less than or equal to 6.5%. The outcome measure was evaluated based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change from baseline in number of participants in glycaemic categories (normo-glycaemia, pre-diabetes and type 2 diabetes) at baseline (week 0) to week 44 are presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change from baseline in number of participants in antihypertensive medication (decrease, no change, increase) at baseline (week 0) to week 44 are presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change from baseline in number of participants in lipid-lowering medication (decrease, no change, increase) at baseline (week 0) to week 44 are presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change from basline in number of participants with concomitant oral antidiabetic medication (decrease, no change, increase) at baseline (week 0) to week 44 are presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Change from baseline in number of participants in fatty liver index (FLI) at baseline (week 0) to week 44 are presented. The fatty liver index is based on an algorithm including body mass index, waist circumference, triglycerides and gamma-glutamyl-transferase. The FLI scores less than (\<) 30 indicates no hepatic steatosis (no fatty liver), FLI greater than or equal to (\>=) 30 to less than (\<) 60 indicates intermediate status of hepatic steatosis and \>=60 indicates severe/worse hepatic steatosis. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Number of participants who permanently discontinued randomized trial product from baseline (week 0) to week 44 are presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to last trial-related participant-site contact (week 51).

Time to permanent discontinuation of randomised trial product from baseline (week 0) to week 44 is reported. Participants who permanently discontinued the randomised trial product during the in-trial observation period were only included in the analysis. In-trial observation period: the uninterrupted time interval from the start of randomization (week 0) to date of last contact with trial site (week 51).

An adverse event (AE) defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned are treatment emergent adverse events (TEAE) defined as an event with onset during the on-treatment observation period. On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 44) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.

A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. SAE results occurred from week 0 to week 51 is presented based on the on-treatment observation, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 44) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.

Hypoglycaemic episodes with onset during on-treatment observation period were considered treatment-emergent. Number of treatment emergent severe or BG confirmed symptomatic hypoglycaemia episodes in participants with T2D at week 0 with onset during on-treatment observation period were presented.

Change in pulse from baseline (week 0) to week 44 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 44) plus a 7 week follow-up period and excluding any off-treatment time intervals.

Change in amylase measured in units/liter (U/L) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 44) plus a 7 week follow-up period and excluding any off-treatment time intervals.

Change in lipase measured in units/liter (U/L) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 44) plus a 7 week follow-up period and excluding any off-treatment time intervals.

Change in calcitonin measured in units/liter (U/L) from baseline (week 0) to week 44 is presented as ratio to baseline. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 44) plus a 7 week follow-up period and excluding any off-treatment time intervals.