Semaglutide for Diabetic Eye Disease

(FOCUS Trial)

Not currently recruiting at 415 trial locations

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Must not be taking: GLP-1 agonists, DPP-4 inhibitors

Disqualifiers: Recent heart events, Severe renal impairment, Cancer history, Pregnancy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effects of semaglutide, a medication, on diabetic eye disease in individuals with type 2 diabetes. The researchers aim to determine if semaglutide can prevent or slow down diabetes-related eye issues over five years. Participants will receive either semaglutide or a placebo (a dummy medicine) alongside their regular diabetes treatment. The trial seeks individuals with type 2 diabetes who have stable blood sugar levels (HbA1c between 7.0-10.0%) and have not recently received eye treatments for diabetic eye conditions. Participants will need to inject the study medicine once a week. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions that participants will continue their diabetes medicines while taking the study drug or placebo.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that semaglutide is usually well-tolerated. Studies indicate it does not increase the risk of eye problems or diabetic retinopathy, which can damage the back of the eye. Some research even suggests it might reduce the risk of vision loss that could lead to blindness. However, some reports link semaglutide to a higher chance of vision issues compared to other diabetes treatments. Overall, the evidence is mixed, but many studies emphasize its safety for eye health. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for diabetic eye disease?

Unlike the standard treatments for diabetic eye disease, which often involve laser therapy or injections directly into the eye, semaglutide offers a unique approach. It's administered as a weekly under-the-skin injection, making it potentially more convenient and less invasive. Semaglutide is a GLP-1 receptor agonist, which is primarily used to manage blood sugar levels in diabetes but may also have protective effects on the eye's blood vessels. Researchers are excited because this could offer a dual benefit for patients with diabetes, managing both blood sugar and eye health simultaneously.

What evidence suggests that semaglutide might be an effective treatment for diabetic eye disease?

In this trial, participants will receive either semaglutide or a placebo. Research has shown that semaglutide, a medication commonly used for diabetes, may help lower the risk of vision loss. One study found it reduced the risk of vision loss leading to blindness by 24.2% and decreased the chance of serious eye problems by 30.2%. Although a few individuals taking semaglutide experienced eye issues like bleeding in the eye, this was a small number. Most people using semaglutide did not see their diabetic eye disease worsen. Overall, semaglutide appears promising in managing diabetic eye disease. ^{2 5 6 7 8}

Who Is on the Research Team?

Clinical Reporting Anchor and Disclosure (1452)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

Adults with type 2 diabetes and moderate diabetic eye disease, who haven't had certain eye treatments or conditions that could affect the study. They should have an HbA1c level between 7.0-10.0% and not be on any GLP-1 receptor agonists or DPP-4 inhibitors from randomisation.

Inclusion Criteria

I haven't had eye treatments for diabetes-related conditions in the last 6 months.

Your HbA1c level is between 7.0% and 10.0%.

My eyes are healthy except for diabetes-related issues.

Exclusion Criteria

I am scheduled for a procedure to improve blood flow to my heart, neck, or limbs.

My kidney function is low, with an eGFR under 30.

Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive semaglutide or placebo once weekly as a subcutaneous injection added to standard of care

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo (semaglutide)
• Semaglutide

Trial Overview

The trial is testing if semaglutide can help diabetic eye disease compared to a placebo over five years. Participants will inject either semaglutide or placebo once a week alongside their regular diabetes medication.

How Is the Trial Designed?

Group I: Semaglutide Experimental Treatment 1 Intervention

Participants will receive semaglutide once weekly as subcutaneous (s.c., under the skin) injection added to standard of care.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive placebo (semaglutide) once weekly as subcutaneous subcutaneous (s.c., under the skin) injection added to standard of care.

Semaglutide is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Canada as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Japan as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Wegovy for:

• Obesity

Approved in United States as Rybelsus for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Published Research Related to This Trial

Semaglutide, a GLP-1 receptor agonist, has been shown to effectively improve blood sugar control and promote weight loss, with a favorable safety profile similar to other GLP-1RAs, based on extensive phase 3 trials including cardiovascular outcome studies.

The most common side effects of semaglutide are mild-to-moderate gastrointestinal disturbances, and while there are concerns about pancreatic and thyroid cancer, no unexpected safety issues have been identified, making it a beneficial option for patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Semaglutide. Smits, MM., Van Raalte, DH.[2023]

Semaglutide, a long-acting GLP-1 receptor agonist, has been shown to significantly reduce HbA1c, fasting plasma glucose, body weight, and blood pressure in over 9,000 patients with type 2 diabetes, demonstrating greater efficacy than other GLP-1RAs.

While semaglutide has a low risk of hypoglycemia, it is associated with gastrointestinal side effects, and there is a warning regarding an increased risk of diabetes-related retinopathy in patients with preexisting conditions, necessitating further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical potential of treatment with semaglutide in type 2 diabetes patients. Røder, ME.[2020]

In a study of 20 patients with type 2 diabetes in Slovenia, oral semaglutide significantly reduced HbA1c levels and fasting plasma glucose, indicating its efficacy in improving glycaemic control.

Patients reported high satisfaction with the treatment, and while some experienced mild gastrointestinal side effects, the overall safety profile was considered good, suggesting that oral semaglutide is a promising option for diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience. Janić, M., Jovanović, M., Janež, A., et al.[2023]

Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.

The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. Paquot, N.[2022]

Semaglutide, a GLP-1 receptor agonist for type 2 diabetes, has a good safety profile but is associated with a high prevalence of gastrointestinal disorders, reported in over 3500 cases (53.2%).

Compared to other diabetes medications like sitagliptin and empagliflozin, semaglutide has a significantly higher number of reported gastrointestinal adverse events, indicating the need for careful monitoring in certain patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database. Cabral Lopes, A., Roque, F., Lourenço, O., et al.[2023]

Semaglutide, a GLP-1 receptor agonist with a long half-life, effectively promotes insulin secretion in a glucose-dependent manner, making it a valuable treatment for type 2 diabetes, approved for use worldwide and in Japan since 2018.

Oral semaglutide (Rybelsus®) is the first GLP-1 receptor agonist available in pill form, showing continuous benefits in glycemic control for patients with type 2 diabetes across various stages, as demonstrated in multiple global clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New drug for type 2 diabetes: introduction of oral Semaglutide (Rybelsus® tablets), an oral GLP-1 receptor agonist]. Miyasaka, K.[2022]

Semaglutide (Ozempic®) is an effective once-weekly treatment for type 2 diabetes, showing superior glucose-lowering effects and greater weight loss compared to other GLP-1 receptor agonists in Phase III clinical trials.

It is approved for use in Belgium for patients with type 2 diabetes who have not achieved adequate control with other antidiabetic therapies, particularly in those with a body mass index of 30 kg/m² or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. Scheen, AJ.[2019]

In a meta-analysis of 23 randomized trials involving 22,096 patients with type 2 diabetes, semaglutide was not found to significantly increase the overall risk of diabetic retinopathy (DR) compared to control groups.

However, the analysis indicated that semaglutide was associated with a higher risk of DR in specific subgroups, particularly in patients aged 60 years or older and those with a diabetes duration of 10 years or more, suggesting that caution is warranted in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide and Diabetic Retinopathy Risk in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials. Wang, F., Mao, Y., Wang, H., et al.[2022]

Semaglutide, a glucagon-like peptide-1 receptor agonist, is effective for treating type 2 diabetes and obesity, providing significant weight loss and cardiovascular benefits, making it crucial for high-risk patients.

However, during the SUSTAIN clinical trial program, a safety concern arose regarding the worsening of diabetic retinopathy, potentially linked to rapid reductions in HbA1c levels, which requires further investigation and careful clinical management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide-eye-catching results. Cigrovski Berkovic, M., Strollo, F.[2023]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11997011/

Semaglutide and the Retina - PMC

In pre‐cardiovascular outcome trials (CVOT) of semaglutide, baseline history of diabetic retinopathy was present in 3.7%–14.5% of participants, ...

2.

njretina.com

njretina.com/wp-content/uploads/2023/06/NJR_Newsletter_JUNE_23_wEB_m1.pdf

Semaglutide (Ozempic®, Wegovy®) and its effect on ...

However, despite its clear benefits, semaglutide has also been linked to an increased incidence of diabetic retinopathy (DR). The SUSTAIN clinical trial program ...

3.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2837378

GLP-1 Receptor Agonists and Sight-Threatening ...

Furthermore, GLP-1 RA use was associated with a 24.2% reduction in the risk of vision loss progressing to blindness, with 30.2% reduction in ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8727607/

Semaglutide and the risk of diabetic retinopathy—current ...

16 (1%) patients developed vitreous haemorrhage in semaglutide group when compared to only 7 (0.4%) patients in the placebo group and 5 (0.3%) ...

5.

aao.org

aao.org/newsroom/news-releases/detail/study-weight-loss-drug-doesnt-worsen-eye-disease

Popular Weight Loss Drug Does Not Appear to Worsen ...

It appears that most people taking semaglutide do not develop diabetic retinopathy or experience a worsening of existing diabetic retinopathy.

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40810985/

Ocular Adverse Events With Semaglutide: A Systematic ...

These findings suggest that semaglutide was not associated with an increased risk of eye disorders or diabetic retinopathy.

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S2666396124000128

Long-term use of semaglutide and risk of diabetic ...

Semaglutide use was not associated with increased risk of progression of DR, visual loss, or an increased number of intravitreal injections over a 3-year ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11974072/

Increased vision impairment reports linked to semaglutide

These findings suggest a potentially elevated risk of vision impairment with semaglutide use compared to other diabetes and weight loss medications.