Semaglutide for Diabetic Eye Disease

(FOCUS Trial)

Recruiting at 320 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

1500 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug semaglutide for diabetic eye disease?

Semaglutide is effective in lowering blood sugar and promoting weight loss in people with type 2 diabetes, as shown in various clinical trials. However, one study (SUSTAIN 6 trial) found a higher rate of eye complications in patients treated with semaglutide compared to those given a placebo. ^{1 2 3 4 5}

Is semaglutide safe for humans?

Semaglutide is generally safe for humans, with most side effects being mild to moderate, such as stomach issues like nausea and vomiting, which often improve over time. There is a small risk of gallbladder problems and a potential increase in diabetic eye disease in some patients, so monitoring is advised, especially for those with existing eye conditions. ^{1 4 5 6 7}

What makes the drug Semaglutide unique for treating diabetic eye disease?

Semaglutide is unique because it is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that can be administered either orally or as a once-weekly injection, offering convenience and flexibility. It is primarily used for type 2 diabetes and obesity, but its potential impact on diabetic eye disease is being explored, although there are concerns about its effects on diabetic retinopathy. ^{1 2 3 8 9}

Research Team

Clinical Reporting Anchor and Disclosure (1452)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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, 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]

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]

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]

References

1. Belgium pubmed.ncbi.nlm.nih.gov

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

2. Japan pubmed.ncbi.nlm.nih.gov

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

3. New Zealand pubmed.ncbi.nlm.nih.gov

Semaglutide and Diabetic Retinopathy Risk in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience. [2023]

5. Belgium pubmed.ncbi.nlm.nih.gov

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety of Semaglutide. [2023]

7. England pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

Semaglutide-eye-catching results. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database. [2023]