Assessment will be based on pounds lost between baseline and final study visit.

Measured in percentage (%)-point.

Change in HbA1c (percentage) from baseline (week 26) to week 52 is presented. The outcome data was evaluated based on the on-intensification phase. On-intensification phase was observed data at planned visits from time of the intensification week 26 until the end of treatment week 52, i.e., for participants who permanently discontinued either insulin icodec or semaglutide treatment, post-discontinuation observations were not included.

Percentage change in body weight from baseline (week 0) to end of treatment (week 44) is presented.

Number of participants who achieved ≥5% body weight reduction at the end of treatment (week 44) 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.

Measured in percentage (%)

Change in gene expression assessed by scRNAseq (cells in CSF) from baseline (week 0) to week 12 is presented. Change in gene expression is presented as the mean number of differentially expressed genes (DEG).

Change in gene expression assessed by scRNAseq (cells in blood) from baseline (week 0) to week 12 is presented. Change in gene expression is presented as the mean number of differentially expressed genes.

Measured in percentage (%)

Measured as count of participants

Number of participants who achieve body weight reduction \>=5% is presented. Yes defines participants who achieved body weight reduction \>= 5% and No defines participants who did not achieve body weight reduction \>=5%.

Relative change in body weight from baseline (week 0) to end of treatment (week 72) is presented.

Number of participants who achieve body weight reduction \>=5% from baseline (week 0) is presented in categories as "yes" or "no" where "yes" defines participants who achieved body weight reduction \>=5% and "no" defines participants who did not achieve body weight reduction \>=5%.

Percentage change in body weight from baseline (week 0) to end of treatment (week 64) is presented.

Change in HbA1c (Noninferiority) from baseline (Week 0) to end of treatment (Week 40) were reported. Here noninferiority was assessed based on the clinically acceptable margin of 0.3%-point for the mean treatment difference in HbA1c.

Change in percentage (%) of body weight from baseline (week 0) to end of treatment (week 44) is presented in this outcome measure and it was evaluated based on the data from in-trial observation period. For end of treatment visit, data collected up to week 49 during the in-trial observation period is included in this Outcome Measure. In-trial observation period: The time period where the participants were assessed in the study. The in-trial observation period begins on the date of randomization (week 0) and ends at the end of study visit (week 49).

Change in percentage (%) of body weight from baseline (week 0) to end of treatment (week 44) is presented in this endpoint. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: The time period where participants were treated with trial product. It started from the date of first trial product administration (week 0) to the date of last trial product administration (week 44) including 2 weeks of follow up. It excludes off treatment period which is defined as at least 2 consecutive missed doses.

Number of participants who achieved body weight reduction more than or equal to 5 percent is presented at week 44 in this outcome measure and it was evaluated based on the data from in-trial observation period. For end of treatment visit, data collected up to week 49 during the in-trial observation period is included in this Outcome Measure. In-trial observation period: The time period where the participants were assessed in the study. The in-trial observation period begins on the date of randomization (week 0) and ends at the end of study visit (week 49).

Number of participants who achieved body weight reduction more than or equal to 5 percent is presented at week 44 in this endpoint. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: the time period where partici-pants were treated with trial product. It started from the date of first trial product administration (week 0) to the date of last trial product administration (week 44) including 2 weeks of follow up. It excludes off treatment period which is defined as at least 2 consecutive missed doses.

Count of participants

WOMAC is a disease-specific patient-reported outcome measure designed to assess changes in symptoms and lower extremity functioning associated with treatment in patients with osteoarthritis of the hip and/or knee. WOMAC is a 24 item questionnaire which assesses clinically important, participant-relevant symptoms in area of pain, stiffness, and physical function in participants with osteoarthritis (OA). It consists of 3 subscales: pain, stiffness and physical function. The WOMAC raw pain score is derived as the sum of the 5 item scores in the pain domain. It will be normalised and expressed on a 0-100 scale. This is done by dividing raw score by the highest possible value of the raw score for the pain domain (i.e. 50) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.

Number of participants who achieved weight loss greater than or equal to 5% of their baseline body weight (yes/no) at end-of-treatment (week 68) is presented.

Change in body weight from randomisation (week 0) to end of treatment (week 52) is presented. The endpoint was evaluated based on the data from in-trial observation period which was defined as the time period where the participant was assessed in the main phase of the study. The 'in-trial' (main phase) observation period for a participant begins on the date of randomisation and ends at the first of the following dates (both inclusive): safety visit, withdrawal of consent, last contact with participant (for participants lost to follow-up), death.

Number of participants in glycaemic categories, "normoglycaemia, pre-diabetes and type 2 diabetes" at Week 52 are presented. These categories were set as per the following criteria: 1) Normoglycaemia: glycosylated haemoglobin (HbA1c) lesser than (\<) 6.0 percentage (%) and fasting plasma glucose (FPG) lesser than (\<) 5.5 millimoles per liter (mmol/L). 2) Pre-diabetes: 6.0% lesser than or equal (≤) HbA1c lesser than (\<) 6.5% or 5.5 mmol/L lesser than or equal (≤) FPG lesser than (\<) 7.0 mmol/L or non-verified type 2 diabetes. 3) Type 2 diabetes: HbA1c greater than or equal (≥) 6.5% or FPG greater than or equal (≥) 7.0 mmol/L.

Score on a scale of 0 to 100 where the score 100 means the least burden for the participant.

Percentage (%)

Score on scale (0 to 18) Measures the impact of cognitive decline on daily function using the following six domains commonly affected in Alzheimer's disease: * Cognitive domains: memory, orientation, and judgement and problem solving * Function domains: community affairs, home and hobbies, and personal care Based on clinical information obtained from the subject and informant, an individual box score ranging from 0 to 3 is determined that represents "none" to "severe" impairment for each of the six domains. The CDR-Sum of Boxes (CDR-SB) score will be derived by adding the individual scores of the six domains at a given time point. The total CDR-SB score ranges from 0 to 18 with higher scores representing greater impairment.

Change in kidney oxygenation in cortex assessed by BOLD (blood oxygenation level dependent) MRI from baseline (week 0) to end of treatment (week 52) is presented. R2\* is a measure used in BOLD MRI to indicate the level of tissue oxygenation. A higher R2\* value means lower tissue oxygenation while a lower R2\* value means higher tissue oxygenation.

Change in kidney oxygenation in medulla assessed by BOLD (blood oxygenation level dependent) MRI from baseline (week 0) to end of treatment (week 52) is presented. R2\* is a measure used in BOLD MRI to indicate the level of tissue oxygenation. A higher R2\* value means lower tissue oxygenation while a lower R2\* value means higher tissue oxygenation.

Change in global kidney perfusion assessed by phase contrast MRI from baseline (week 0) to end of treatment (week 52) is presented.

Change in kidney inflammation in cortex assessed by T1 mapping MRI from baseline (week 0) to end of treatment (week 52) is presented.

Change in kidney inflammation in medulla assessed by T1 mapping MRI from baseline (week 0) to end of treatment (week 52) is presented.

Count of subject

Count of subject

Count of subject

The KCCQ is a standardized 23-item, self-administered instrument that quantifies heart failure symptoms (frequency, severity, and recent change), physical limitation, quality of life, and social limitation. The overall summary score and all domains have been independently demonstrated to be valid, reliable, and responsive to clinical change. KCCQ-CSS includes the symptom and physical limitation domains of the KCCQ. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.

Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment. Percentage point refers to arithmetic difference between two percentages.

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).

Percentage point

Change in maximum walking distance on a constant load treadmill test is presented. The constant-load treadmill test with fixed speed (3.2 km/h, 2 mph) and fixed inclination (12%) is a standardised method for functional assessment of patients with peripheral artery disease. Participants continue on the treadmill after indicating onset of pain and should continue as long as possible until pain limits further activity. This distance is noted as the maximum walking distance. The outcome measure was evaluated based on data from in-study observation period. In-study observation period is defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.

Change in BMI (%) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.

Change from baseline (week 0) to week 68 in body weight (%) is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.

Change in HbA1c from baseline to week 26 in percentage (%) point of HbA1c is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period and in-trial observation period. On-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication. In-trial observation period: the time period where participants were considered to be in the trial, regardless of discontinuation of trial product or initiation of rescue medication.

Change from baseline (week 0) to week 40 in glycosylated haemoglobin (HbA1c) was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first; and 'In-trial' observation period which started at the date of randomisation and ended at the first of the following dates, both inclusive: end-of-treatment visit (week 40), death, participant withdrew informed consent, last contact for participant lost to follow-up.

Number of participants with first occurrence of EAC (event adjudication committee) confirmed major adverse cardiovascular event (MACE), a composite end-point. i.e., from time of randomization to first occurrence of cardiovascular (CV) death, non-fatal myocardial infarction and non-fatal stroke combined data during in-trial period were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

Number of participants with first composite renal event i.e., from time of randomization to first occurrence of an onset of persistent greater than or equal to (≥) 50 percent (%) reduction in estimated glomerular filtration rate (eGFR) (chronic kidney disease - epidemiology collaboration \[CKD-EPI\]), onset of persistent eGFR (CKD-EPI) \<15 milliliter per minute per 1.73 meter square (mL/min/1.73m\^2), initiation of chronic renal replacement therapy (dialysis or kidney transplantation), renal death, and cardiovascular (CV) death combined data were reported in this outcome measure.

Percentage of subjects (yes/no).

Number of participants who achieved greater than or equal to (≥) 5% weight loss at week 68 for in-trial observation period is presented. In the reported data, 'Yes' infers the number of participants who have achieved ≥ 5% weight loss, whereas 'No' infers the number of participants who have not achieved ≥ 5% weight loss. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75).

Number of participants with first occurrence of composite outcome measure consisted of CV death (undetermined cause of death presumed CV death), non-fatal MI, or non-fatal stroke are presented. The outcome measure was evaluated based on data from in-trial observation period. In-trial observation period defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death.

Percentage change in body weight for both in-trial and on-treatment observation period from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site. On-treatment observation period: the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as \>2 consecutive missed doses (corresponding to \>2 weeks off-treatment).

Number of participants who achieved greater than or equal to (\>=) 5% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved \>=5% weight loss, whereas 'No' infers the number of participants who have not achieved \>=5% weight loss. The outcome measure was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site. On-treatment observation period: the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as \>2 consecutive missed doses (corresponding to \>2 weeks off-treatment).

Change from baseline in HbA1c at week 52 is presented. Data is reported for 'on-treatment' observation period: from the date of first dose of trial product (week 0) to the last date on trial product with a visit window of +7 days (week 52).

Number of participants who achieved greater than or equal to (≥) 5% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved ≥ 5% weight loss, whereas 'No' infers the number of participants who have not achieved ≥ 5% weight loss. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption.

Change in body weight from baseline (week 20) to week 68 is presented. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).

Change in body weight (%) from baseline (week 0) to week 68 is presented. Results are based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75). 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 68) plus a 2-week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.

Number of participants who achieved weight reduction ≥5% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. 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 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.

Number of participants who achieved weight loss more than or equal to 5% (yes/no) at week 68 are presented. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption.

Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 26. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. The endpoint was also analysed based on data from the on-treatment without rescue medication observation period. On-treatment without rescue medication observation period started at the date of the first dose of trial product and includes the period after initiation of rescue medication, if any, and excludes the period after premature trial discontinuation, if any.

Number of participants experiencing a first event of a MACE, defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 57 (52-week treatment period plus the 5-week follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Participants who achieved HbA1c \<7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at week 52. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 26. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

Estimated mean change from baseline in HbA1c at week 30. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening \[\<= 8.0% or \> 8.0%\] crossed with use of metformin \[yes or no\]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using mixed model for repeated measurements.

An adverse events (AEs) was defined as any unfavourable 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 here are treatment emergent adverse events (TEAE) defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment (week 0-30 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).

Change in HbA1c from baseline to week 30.

Change in HbA1c from baseline until week 56.Full analysis set (FAS=1225) included all randomised subjects who had received at least one dose of randomised semaglutide or sitagliptin.

Mean change in HbA1c from baseline to week 56.

Percentage of subjects experiencing a first event of a major adverse cardiovascular event (MACE), defined as cardiovascular (CV) death, non-fatal myocardial infarction (MI), or non-fatal stroke.

Change in HbA1c from baseline (week 0) to week 32 is presented. The endpoint was evaluated based on the data from in-trial period. The in-trial period is defined as the time interval from date of randomization to date of last contact with trial site. The on-treatment without rescue medication period is a subset of the 'on-treatment' observation period and represents the time period where subjects are considered exposed to trial product but have not initiated any rescue medications.

A TEAE is defined as an event that has onset after administration of trial product and no later than the follow-up visit or is present before trial product administration and increases in after the first dose of trial product and no later than the follow-up visit.

Percentage change in body weight (%) from week 32 to week 48 is presented. For descriptive analysis and statistical analysis the endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site.

The intensity of injection site pain was measured on a visual analogue scale (VAS). The VAS consists of a horizontal 100 millimetres (mm) line where 0 mm corresponded to no pain and 100 mm corresponded to unbearable pain. After each injection, the participants rated their pain perception at the VAS by marking a vertical line across the 100 mm line. The distance (mm) between the endpoint "no pain" and the vertical line on the VAS was recorded and analysed.

NASH resolution defined by NASH clinical research network (CRN) as lobular inflammation of 0 or 1; hepatocellular ballooning reduced to 0; both criteria were necessary conditions. Hepatocellular ballooning ranges from 0-2; lobular inflammation ranges from 0-3, higher scores indicating more severe hepatocellular ballooning/lobular inflammation. Worsening of NASH defined by NASH CRN as increase of at least 1 stage of either lobular inflammation, hepatocyte ballooning or steatosis. Worsening of fibrosis defined by increase in fibrosis at least 1 stage of Kleiner fibrosis classification: fibrosis stages range from 0-4, higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

NASH resolution defined by NASH clinical research network as lobular inflammation of 0 or 1 and hepatocellular ballooning reduced to 0; both criteria were necessary conditions. Hepatocellular ballooning ranges from 0-2; lobular inflammation ranges from 0-3, with higher scores indicating more severe hepatocellular ballooning or lobular inflammation. Worsening of fibrosis defined by an increase in fibrosis at least one stage of Kleiner fibrosis classification: fibrosis stages range from 0-4, with higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Endpoint was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Relative change from baseline (week 0) in body weight was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline body weight as covariate. In-trial observation period was defined as the period from randomisation to last contact with trial site.

Change from baseline in HbA1c was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the last observation carried forward (LOCF) approach.

M-value from the HEC is calculated from glucose infusion rate (GIR) over the last 30 minutes of the clamp, corresponding to steady state. M-value is defined as: (GIR150-180 min normalised by body weight \[milligram per minute per kilogram {mg/min/kg}\]). Measured in mg/min/kg.

Measured in hour\*nanomoles per liter (h\*nmol/L).

Measured in hour\*nanomoles per liter (h\*nmol/L).

measured in h\*nmol/L

measured inh\*ng/mL

Measured in h\*pg/mL

Measured in h\*pg/mL

nmol\*h/L

ng\*h/mL

nmol\*h/L

nmol\*h/L

nmol\*h/L

h\*nmol/L

nmol/L

h\*nmol/L

nmol/L

h\*nmol/L

nmol/L

hours\*nmol/L

nmol/L

h\*nmol/L

nmol\*h/L

Ratio

Measured in h\*micrograms/mL

Calculated based on semaglutide measured in blood.

Measured in nmol\*h/L

Measured in nmol/L

Measured in nmol·h/L.

Measured in nmol/L.

Calculated based on plasma SNAC activity measured in blood.

Calculated based on plasma SNAC activity measured in blood.

Measured in KPa

Calculated based on semaglutide measured in blood.

Calculated based on semaglutide measured in blood.