Overview

This study is being done to look at the safety and effect of NNC0487-0111 in people with Heart Failure with preserved Ejection Fraction (HFpEF) or Heart Failure with mildly reduced Ejection Fraction (HFmrEF) and excess body weight when compared to placebo. The purpose of this clinical study is to find out if NNC0487-0111 is safe and effective for treating people who have HFpEF or HFmrEF and excess body weight. Participants will get NNC0487-0111 or placebo by injection once a week. Which treatment participants get is decided by chance. NNC0487-0111 is a new medicine that doctors cannot prescribe yet, but it has been tested in people before.

Eligibility

Inclusion Criteria:

• Body Mass Index (BMI) greater than or equal to (\>=) 30 kilograms per square metre (kg/m\^2) at screening.
• Diagnosis of HF with New York Heart Association (NYHA) class II-IV and in stable condition at screening, at the discretion of the investigator.

For participants with Type 2 Diabetes (T2D) at screening:

\- Diagnosed with T2D \>= 30 days before screening.

Exclusion Criteria:

• MI, stroke, unstable angina pectoris or worsening HF leading to either hospitalization or intravenous loop diuretics within 30 days prior to the day of screening and until randomization.
• HF due to infiltrative cardiomyopathy (e.g., sarcoid, amyloid), arrhythmogenic right ventricular cardiomyopathy, Takutsubo cardiomyopathy, Chagas cardiomyopathy, genetic hypertrophic cardiomyopathy or obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, or uncorrected primary valve disease of moderate or severe degree.
• Severe pulmonary disease including primary pulmonary hypertension, chronic pulmonary embolism, or severe chronic obstructive pulmonary disease (COPD) defined as:
• requiring home oxygen; or - ongoing oral corticosteroid therapy; or - hospital for COPD Exacerbation within 12 months prior to screening.
• Any other condition judged by the investigator to be the cause of HF symptoms (e.g., anaemia, hypothyroidism).

Glycaemia-related:

• History of type 1 diabetes.
• Participant with diabetic retinopathy or maculopathy who received treatment with retinal photocoagulation, vitrectomy or anti-Vascular Endothelial Growth Factor (anti-VEGF) within 180 days before screening or who, at the time of screening, are expected to require treatment within 180 days after screening. Diabetic retinopathy or maculopathy must be verified by an eye examination performed within 90 days before screening or in the period between screening and randomization. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
• Glycated haemoglobin (HbA1c) greater than (\>) 10 percent (%) (86 \[millimoles per mole\] mmol/mol) as measured by local or central laboratory at screening.