Patients will receive 4.5 mg of placebo (NNC0174-0833) once a week as injections for 26 weeks.

Patients will receive 1.2 mg of placebo (NNC0174-0833) once a week as injections for 26 weeks.

Patients will receive 0.6 mg of placebo (NNC0174-0833) once a week as injections for 26 weeks.

Patients will receive 0.3 mg of NNC0174-0833 once a week as injections for 26 weeks.

Patients will receive 3.0 mg of liraglutide once daily as injections for 26 weeks.

Patients will receive placebo 3.0 mg(liraglutide) once daily as injections for 26 weeks.

Participants will get one dose of Placebo (NNC0174-0833) once weekly. The medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm using NovoPen® 4. Participants will gradually increase the dose until they reach the target dose, and will continue on the this dose once weekly up to 26 weeks.

Participants will get one dose of liraglutide 3.0 mg once daily. The medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm using pre-filled PDS290 pen-injector. Participants will gradually increase their dose every week until they reach the target dose of 3.0 mg daily. The participants will continue on 3.0 mg of liraglutide, once daily up to 26 weeks.

Participants will get one dose of Placebo (liraglutide 3.0 mg) once daily. The medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm using pre-filled PDS290 pen-injector. Participants will gradually increase their dose every week until they reach the target dose of 3.0 mg. The participants will continue on Placebo (liraglutide 3.0 mg), once daily up to 26 weeks.

Change in body weight (Kg) from week 0 to week 26 is presented. 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. Follow-up time for positive antibodies was not included in the in-trial period.

Change in waist circumference from week 0 to week 26 is presented. 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. Follow-up time for positive antibodies was not included in the in-trial period.

Change in total cholesterol from week 0 to week 26 is presented. 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. Follow-up time for positive antibodies was not included in the in-trial period.

Change in HDL cholesterol from week 0 to week 26 is presented. 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. Follow-up time for positive antibodies was not included in the in-trial period.

Change in LDL cholesterol from week 0 to week 26 is presented. 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. Follow-up time for positive antibodies was not included in the in-trial period.

Change in VLDL cholesterol from week 0 to week 26 is presented. 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. Follow-up time for positive antibodies was not included in the in-trial period.

Change in triglycerides from week 0 to week 26 is presented. 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. Follow-up time for positive antibodies was not included in the in-trial period.

Change in HbA1c (measured as percentage point of HbA1c) from week 0 to week 26 is presented. 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. Follow-up time for positive antibodies was not included in the in-trial period.

Change in HbA1c (measured as millimoles per mole (mmol/mol)) from week 0 to week 26 is presented. 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. Follow-up time for positive antibodies was not included in the in-trial period.

Change in FPG (measured as mmol/L)) from week 0 to week 26 is presented. 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. Follow-up time for positive antibodies was not included in the in-trial period.

Change in FPG (measured as milligrams per decilitre (mg/dL)) from week 0 to week 26 is presented. 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. Follow-up time for positive antibodies was not included in the in-trial period.

In the below table, fasting insulin data at week 0 and at week 26 is presented. 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. Follow-up time for positive antibodies was not included in the in-trial period.

Percentage change in HOMA-IR from week 0 to week 26 is presented. Insulin resistance is a condition in which cells fail to respond to normal actions of hormone in body. HOMA-IR is calculated using a subject's fasting plasma insulin and glucose levels. HOMA-IR = fasting serum insulin (micro international units per milliliter (μU/ml)) × fasting plasma glucose (millimoles per liter (mmol/l)) / 22.5. HOMA-IR scores are classified as follows: less than 1.0: considered Insulin sensitive, 0.5-1.4: considered Healthy, Above 1.8: considered Early insulin resistance; Above 2.7 is considered significant insulin resistance. HOMA-IR score ranges from 0-infinity (no upper limit). Higher the score, higher the level of insulin resistance. Endpoint was evaluated based on 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. Follow-up time for positive antibodies was not included in in-trial period.

Change between the value of HOMA-beta cell function collected at Week 26 and HOMA-beta cell function collected at Week 0 is presented. The homeostatic model assessment estimates steady state beta cell function as a percentage of a normal reference population (%B). HOMA %B = 20 * insulin (micro international units per milliliter (µIU/mL)) / fasting plasma glucose (millimoles per liter (mmol/L)) - 3.5. HOMA-beta score ranges from minus infinity to infinity (no limits). The higher the score the better beta-cell function for HOMA-beta. 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. Follow-up time for positive antibodies was not included in the in-trial period.

An adverse event (AE) was any untoward medical occurrence in a clinical trial participant administered or used a medicinal product, whether or not considered related to the medicinal product or usage. All AEs reported here are TEAEs. TEAE is defined as an event that had onset date during the on-treatment period. The endpoint was evaluated based on the data from on-treatment period which started from the date of first trial product administration to date of last trial product administration excluding potential off-treatment time intervals triggered by at least 6 consecutive missed doses for cagrilintide or 6 consecutive weeks of missed dosing with liraglutide.

An AE was any untoward medical occurrence in a clinical trial participant administered or used a medicinal product, whether or not considered related to the medicinal product or usage. Serious AE is an AE that resulted in death, life threatening, persistent or significant incapacity or substantial disruption of ability to conduct normal life functions, hospitalization or prolongation of existing hospitalization, congenital anomaly or birth defect, important medical events that may not result in death, be life threatening, or require hospitalization. All SAEs reported in the below table are TESAEs. The endpoint was evaluated based on the data from on-treatment period which started from the date of first trial product administration to date of last trial product administration excluding potential off-treatment time intervals triggered by at least 6 consecutive missed doses for cagrilintide or 6 consecutive weeks of missed dosing with liraglutide.

Number of participants with occurrence of anti-drug antibodies towards cagrilintide from randomisation from week 0 to week 32 is presented. The endpoint was evaluated based on the data from in-trial period. The in-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. Follow-up time for positive antibodies was not included in the in-trial period. This endpoint is applicable only for the cagrilintide treatment arms.

Blood pressure was measured in a sitting position after 5 minutes of rest. The end point is evaluated while the subject is treatment-adherent. A participant is treatment adherent until the first time of non-adherence defined as: a) the participant has not been dosed with trial product within the prior 14 days; b) the participant has received other weight management drug or bariatric surgery c) the participant has not reached target dose at a pre-specified week d) After the pre-specified evaluation week for the target dose, the participant has not received the target dose +/- 10 % within the prior 14 days. This endpoint is applicable only for the cagrilintide treatment arms.

Blood pressure was measured in a sitting position after 5 minutes of rest. The end point is evaluated while the subject is treatment-adherent. A participant is treatment adherent until the first time of non-adherence defined as: a) the participant has not been dosed with trial product within the prior 14 days; b) the participant has received other weight management drug or bariatric surgery c) the participant has not reached target dose at a pre-specified week d) After the pre-specified evaluation week for the target dose, the participant has not received the target dose +/- 10 % within the prior 14 days. This endpoint is applicable only for the cagrilintide treatment arms.

Change in pulse from week 0 to week 26 is presented. The endpoint was evaluated based on the data from on-treatment period which started from the date of first trial product administration to date of last trial product administration excluding potential off-treatment time intervals triggered by at least 6 consecutive missed doses for cagrilintide or 6 consecutive weeks of missed dosing with liraglutide.

In the below table, hsCRP data at week 0 and at week 26 is presented. The endpoint was evaluated based on the data from on-treatment period which started from the date of first trial product administration to date of last trial product administration excluding potential off-treatment time intervals triggered by at least 6 consecutive missed doses for cagrilintide or 6 consecutive weeks of missed dosing with liraglutide.

Due to the assay development issue faced by the laboratory, the Plasminogen Activator Inhibitor-1 (PAI-1) activity (mg/L) was not performed in the study.

Change in renin activity from week 0 to week 26 is presented. The endpoint was evaluated based on the data from on-treatment period which started from the date of first trial product administration to date of last trial product administration excluding potential off-treatment time intervals triggered by at least 6 consecutive missed doses for cagrilintide or 6 consecutive weeks of missed dosing with liraglutide.

Change in aldosterone from week 0 to week 26 is presented. The endpoint was evaluated based on the data from on-treatment period which started from the date of first trial product administration to date of last trial product administration excluding potential off-treatment time intervals triggered by at least 6 consecutive missed doses for cagrilintide or 6 consecutive weeks of missed dosing with liraglutide.

Participants were to receive once weekly s.c. injection of cagrilintide for 26 weeks, using NovoPen® 4 pen-injector. Participants initially received 0.6 mg of cagrilintide and the dose was then escalated every other week until the target dose of 1.2 mg was reached: 0.6 mg (week 0) and 1.2 mg (week 2 to week 26).

Participants were to receive once weekly s.c. injection of cagrilintide for 26 weeks, using NovoPen® 4 pen-injector. Participants initially received 0.6 mg of cagrilintide and the dose was then escalated every other week until the target dose of 2.4 mg was reached: 0.6 mg (week 0), 1.2 mg (week 2), 2.4 mg (week 4 to week 26).

Participants were to receive once weekly s.c. injection of cagrilintide for 26 weeks, using NovoPen® 4 pen-injector. Participants initially received 0.6 mg of cagrilintide and the dose was then escalated every other week until the target dose of 4.5 mg was reached: 0.6 mg (week 0), 1.2 mg (week 2), 2.4 mg (week 4), 4.5 mg (week 6 to week 26).

Participants were to receive once daily s.c. injection of liraglutide for 26 weeks, using PDS290 pen-injector. Participants initially received 0.6 mg of liraglutide and the dose was then escalated every other week until the target dose of 3.0 mg was reached: 0.6 mg (week 0), 1.2 mg (week 1), 1.8 mg (week 2), 2.4 mg (week 3), 3.0 mg (week 4 to week 26).

Participants were to receive once weekly / once daily s.c. injection of placebo matched to cagrilintide / liraglutide (0.3 mg, 0.6 mg, 1.2 mg, 2.4 mg or 4.5 mg / 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, 3.0 mg ) for 26 weeks respectively.

Participants were to receive once weekly / once daily s.c. injection of placebo matched to cagrilintide / liraglutide (0.3 mg, 0.6 mg, 1.2 mg, 2.4 mg or 4.5 mg / 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, 3.0 mg ) for 26 weeks respectively.

Week 26 responses were analysed using an analysis of covariance model with randomised treatment as factor and baseline (week 0) body weight as covariate. For each treatment arm, multiple (x1000) imputation of intermittend missing data was done using Markov Chain Monte Carlo, followed by sequential regression for monotone missing values of body weight including sex and region as factors.

Week 26 responses were analysed using an analysis of covariance model with randomised treatment as factor and baseline (week 0) body weight as covariate. For each treatment arm, multiple (x1000) imputation of intermittend missing data was done using Markov Chain Monte Carlo, followed by sequential regression for monotone missing values of body weight including sex and region as factors.

Week 26 responses were analysed using an analysis of covariance model with randomised treatment as factor and baseline (week 0) body weight as covariate. For each treatment arm, multiple (x1000) imputation of intermittend missing data was done using Markov Chain Monte Carlo, followed by sequential regression for monotone missing values of body weight including sex and region as factors.

Week 26 responses were analysed using an analysis of covariance model with randomised treatment as factor and baseline (week 0) body weight as covariate. For each treatment arm, multiple (x1000) imputation of intermittend missing data was done using Markov Chain Monte Carlo, followed by sequential regression for monotone missing values of body weight including sex and region as factors.

Week 26 responses were analysed using an analysis of covariance model with randomised treatment as factor and baseline (week 0) body weight as covariate. For each treatment arm, multiple (x1000) imputation of intermittend missing data was done using Markov Chain Monte Carlo, followed by sequential regression for monotone missing values of body weight including sex and region as factors.

Week 26 responses were analysed using an analysis of covariance model with randomised treatment as factor and baseline (week 0) body weight as covariate. For each treatment arm, multiple (x1000) imputation of intermittend missing data was done using Markov Chain Monte Carlo, followed by sequential regression for monotone missing values of body weight including sex and region as factors.

Week 26 responses were analysed using an analysis of covariance model with randomised treatment as factor and baseline (week 0) body weight as covariate. For each treatment arm, multiple (x1000) imputation of intermittend missing data was done using Markov Chain Monte Carlo, followed by sequential regression for monotone missing values of body weight including sex and region as factors.

Week 26 responses were analysed using an analysis of covariance model with randomised treatment as factor and baseline (week 0) body weight as covariate. For each treatment arm, multiple (x1000) imputation of intermittend missing data was done using Markov Chain Monte Carlo, followed by sequential regression for monotone missing values of body weight including sex and region as factors.

Week 26 responses were analysed using an analysis of covariance model with randomised treatment as factor and baseline (week 0) body weight as covariate. For each treatment arm, multiple (x1000) imputation of intermittend missing data was done using Markov Chain Monte Carlo, followed by sequential regression for monotone missing values of body weight including sex and region as factors.

Week 26 responses were analysed using an analysis of covariance model with randomised treatment as factor and baseline (week 0) body weight as covariate. For each treatment arm, multiple (x1000) imputation of intermittend missing data was done using Markov Chain Monte Carlo, followed by sequential regression for monotone missing values of body weight including sex and region as factors.

Participants were to receive once weekly s.c. injection of cagrilintide for 26 weeks, using NovoPen® 4 pen-injector. Participants initially received 0.6 mg of cagrilintide and the dose was then escalated every other week until the target dose of 2.4 mg was reached: 0.6 mg (week 0), 1.2 mg (week 2), 2.4 mg (week 4 to week 26).

Participants were to receive once weekly s.c. injection of cagrilintide for 26 weeks, using NovoPen® 4 pen-injector. Participants initially received 0.6 mg of cagrilintide and the dose was then escalated every other week until the target dose of 4.5 mg was reached: 0.6 mg (week 0), 1.2 mg (week 2), 2.4 mg (week 4), 4.5 mg (week 6 to week 26).

Participants were to receive once daily s.c. injection of liraglutide for 26 weeks, using PDS290 pen-injector. Participants initially received 0.6 mg of liraglutide and the dose was then escalated every other week until the target dose of 3.0 mg was reached: 0.6 mg (week 0), 1.2 mg (week 1), 1.8 mg (week 2), 2.4 mg (week 3), 3.0 mg (week 4 to week 26).

Participants were to receive once weekly / once daily s.c. injection of placebo matched to cagrilintide / liraglutide (0.3 mg, 0.6 mg, 1.2 mg, 2.4 mg or 4.5 mg / 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, 3.0 mg ) for 26 weeks respectively.

Participants were to receive once weekly s.c. injection of cagrilintide for 26 weeks, using NovoPen® 4 pen-injector. Participants initially received 0.6 mg of cagrilintide and the dose was then escalated every other week until the target dose of 2.4 mg was reached: 0.6 mg (week 0), 1.2 mg (week 2), 2.4 mg (week 4 to week 26).

Participants were to receive once weekly s.c. injection of cagrilintide for 26 weeks, using NovoPen® 4 pen-injector. Participants initially received 0.6 mg of cagrilintide and the dose was then escalated every other week until the target dose of 4.5 mg was reached: 0.6 mg (week 0), 1.2 mg (week 2), 2.4 mg (week 4), 4.5 mg (week 6 to week 26).

Participants were to receive once daily s.c. injection of liraglutide for 26 weeks, using PDS290 pen-injector. Participants initially received 0.6 mg of liraglutide and the dose was then escalated every other week until the target dose of 3.0 mg was reached: 0.6 mg (week 0), 1.2 mg (week 1), 1.8 mg (week 2), 2.4 mg (week 3), 3.0 mg (week 4 to week 26).

Participants were to receive once weekly / once daily s.c. injection of placebo matched to cagrilintide / liraglutide (0.3 mg, 0.6 mg, 1.2 mg, 2.4 mg or 4.5 mg / 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, 3.0 mg ) for 26 weeks respectively.