A Research Study to Look at How Semaglutide Compared to Placebo Affects Diabetic Eye Disease in People With Type 2 Diabetes

Study Overview
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Brief Summary
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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.

Official Title
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Long-term Effects of Semaglutide on Diabetic Retinopathy in Subjects With Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Semaglutide
* Drug: Placebo (semaglutide)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide<br>Participants will receive semaglutide once weekly as subcutaneous (s.c., under the skin) injection added to standard of care. | Drug: Semaglutide<br>* Participants will get one dose of semaglutide once weekly in addition to their diabetes medicines - which treatment they get is decided by chance. Participants will inject the study medicine using a pre-filled PDS290 pen-injector. The medicine must be injected in a skin fold in the stomach, thigh or upper arm once a week. Participants will start with once-weekly doses of 0.25 mg for 4 weeks, then the dose will be gradually increased to 0.5 mg once weekly for 4 weeks, and finally to 1.0 mg once weekly (maximum dose) up to 260 weeks (5 years).<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo (semaglutide) once weekly as subcutaneous subcutaneous (s.c., under the skin) injection added to standard of care. | Drug: Placebo (semaglutide)<br>* Participants will get one dose of placebo (semaglutide) once weekly in addition to their diabetes medicines - which treatment they get is decided by chance. Participants will inject the study medicine using a pre-filled PDS290 pen-injector. The medicine must be injected in a skin fold in the stomach, thigh or upper arm once a week. Participants will start with once-weekly doses of 0.25 mg for 4 weeks, then the dose will be gradually increased to 0.5 mg once weekly for 4 weeks, and finally to 1.0 mg once weekly (maximum dose) up to 260 weeks (5 years).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of at least 3 steps Early Treatment Diabetic Retinopathy Study (ETDRS) subject level progression. | Percentage of subjects (yes/no). | Year 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from randomisation to first at least 3 steps ETDRS subject level progression or central involved diabetic macular oedema (ciDME) in either eye. | Measured in months. | Up to 5 years | 
| Change in visual acuity in the worse seeing eye. | Measured in number of letters using the ETDRS protocol. | Week 0, Year 5 | 
| Change in visual acuity in the better seeing eye. | Measured in number of letters using the ETDRS protocol. | Week 0, Year 5 | 
| Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with focal/grid laser photocoagulation. | Percentage of subjects (yes/no). | Week 0-Year 5 | 
| Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with pan-retinal laser photocoagulation. | Percentage of subjects (yes/no). | Week 0-Year 5 | 
| Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with intravitreal injection with anti-vascular endothelial growth factor (VEGF). | Percentage of subjects (yes/no). | Week 0-Year 5 | 
| Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with intravitreal injection with steroid. | Percentage of subjects (yes/no). | Week 0-Year 5 | 
| Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye with vitrectomy. | Percentage of subjects (yes/no). | Week 0-Year 5 | 
| Presence of at least 3 steps ETDRS subject level improvement. | Percentage of subjects (yes/no). | Year 5 | 
| Presence of at least 2 steps ETDRS subject level progression. | Percentage of subjects (yes/no). | Year 5 | 
| Presence of at least 2 steps ETDRS subject level improvement. | Percentage of subjects (yes/no). | Year 5 | 
| Presence of persistent visual acuity up to 38 ETDRS letters in either eye. | Percentage of subjects (yes/no). | Year 5 | 
| Presence of persistent at least 2 lines (10 letters) ETDRS worsening in visual acuity in either eye from baseline. | Percentage of subjects (yes/no). | Year 5 | 
| Presence of persistent at least 3 lines (15 letters) ETDRS worsening in visual acuity in either eye from baseline. | Percentage of subjects (yes/no). | Year 5 | 
| Presence of persistent at least 2 lines (10 letters) ETDRS improvement in visual acuity in either eye from baseline. | Percentage of subjects (yes/no). | Year 5 | 
| Persistent at least 3 lines (15 letters) ETDRS improvement in visual acuity in either eye from baseline. | Percentage of subjects (yes/no). | Year 5 | 
| Presence of ciDME in either eye. | Percentage of subjects (yes/no). | Year 5 | 
| Change in glycosylated haemoglobin (HbA1c). | Measured in %-points. | Week 0, Year 5 | 
| Change in body weight. | Measured in kg. | Week 0, Year 5 | 
| Change in systolic and diastolic blood pressure. | Measured in mmHg. | Week 0, Year 5 | 
| Change in Lipids: Total-cholesterol, High density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol and triglycerides. | Measured in mmol/L | Week 0, Year 5 |