In this study we will be looking into how CagriSema influences metabolism (the process by which food is used to supply energy for the body) compared to a diet. CagriSema is a new investigational medicine. CagriSema cannot yet be prescribed by doctors but has previously been tested in humans. The study is split into 2 parts. In the first part of the study, participants will either get CagriSema or a weight loss diet (calorie reduced). In the second part of the study,all participants will get CagriSema. Which treatment participants get in the first part of the study is decided by chance. Like all medicines, the study medicine may have side effects. The study will last for about 1.5 years.

Inclusion criteria:

• Male or female (sex assigned at birth).
• Age 18-65 years (both inclusive) at the time of signing the informed consent.
• Body Mass Index (BMI) greater than or equal to (≥) 30.0 kilograms per square meter (kg/m^2) at screening (Visit 1). Excess body weight should be due to excess adipose tissue, as judged by the investigator.

Exclusion criteria:

• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective contraceptive method.
• History of diabetes mellitus of any type, other than gestational diabetes mellitus.
• Claustrophobia or severe discomfort of being confined in small rooms.
• Contraindication for magnetic resonance imaging (MRI) scanning as per local guidance, including physical limitations that prevent the MRI scan.
• Unusual meal habits (including, but not limited to, eating disorders) and special diet requirements or unwillingness to eat the food provided in the study.
• Treatment with metformin or other glucose-lowering agent(s) within 90 days before screening (V1), regardless of indication.
• Treatment with any medication prescribed for the indication of obesity or weight management within 90 days before screening (Visit 1).
• Presence or history of malignant neoplasms or in situ carcinomas (other than basal or squamous cell skin cancer, low-risk prostate cancer, or in situ carcinomas of the cervix or carcinoma in situ/high grade prostatic intraepithelial neoplasia) within 5 years before screening (Visit 1).
• Physical measurement exceeding the dimensions or load capacity of the magnetic resonance imaging (MRI)/dual-energy X-ray absorptiometry (DEXA) scanner.

According to the Novo Nordisk disclosure commitment on novonordisk-trials.com.