This study will look at the long-term effects of semaglutide (active medicine) on diabetic eye disease when compared to placebo (dummy medicine). The study will be performed in people with type 2 diabetes. Participants will either get semaglutide or placebo in addition to their diabetes medicines - which treatment the participant gets is decided by chance. Participants will inject the study medicine using a pen-injector. The medicine must be injected in a skin fold in the stomach, thigh or upper arm once a week. The study will last for 5 years.

Inclusion Criteria:

• Male or female, age greater than or equal to 18 years at the time of signing informed consent
• Diagnosed with type 2 diabetes mellitus.
• HbA1c of 7.0-10.0% (53-86 mmol/mol) (both inclusive).
• Eye inclusion criteria (both eyes must meet all criteria):
• Early Treatment Diabetic Retinopathy Study (ETDRS) level of 10-75 (both inclusive) evaluated by fundus photography and confirmed by central reading centre
• No ocular or intraocular treatment for diabetic retinopathy or diabetic macular oedema six months prior to the day of screening.
• No anticipated need for ocular or intraocular treatment for diabetic retinopathy or diabetic macular oedema within three months after randomisation.
• Best-corrected visual acuity greater than or equal to 30 letters using the ETDRS visual acuity protocol
• No previous treatment with pan-retinal laser photocoagulation
• No substantial non-diabetic ocular condition that, in the opinion of the ophthalmologist, would impact diabetic retinopathy or diabetic macular oedema progression during the trial
• No substantial media opacities that would preclude successful imaging

Exclusion Criteria:

• Any of the following: myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within the past 60 days prior to the day of screening
• Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
• Subjects presently classified as being in New York Heart Association (NYHA) Class IV
• Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of eGFR less than 30 ml/min/1.73 m^2
• Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
• Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using highly effective contraceptive methods
• Concurrent treatment with any GLP-1 receptor agonist or DPP-4 inhibitor from randomisation.
• Receipt of any investigational medicinal product within 30 days before screening
• Previous participation in this trial. Participation is defined as randomisation
• Known or suspected hypersensitivity to trial products or related products
• Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol

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

Sponsor staff involved in the clinical trial is masked according to company standard procedures.