Weight Management for Obesity and Kidney Disease

Overseen By Heather LaPier, BSc

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Western University, Canada

Must not be taking: Semaglutide, Liraglutide, Dulaglutide

Disqualifiers: Type 1 diabetes, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 4

Duration: 26 weeks

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using more than the starting dose of certain medications like semaglutide, liraglutide, or dulaglutide.

What data supports the effectiveness of the drug Semaglutide for weight management in patients with obesity and kidney disease?

Research shows that Semaglutide, a drug used for diabetes, can help with weight loss and improve kidney function in people with obesity and kidney disease. It has been effective in reducing body weight and managing blood sugar levels, which can be beneficial for patients with these conditions. ^{1 2 3 4 5}

Is the treatment safe for humans?

Semaglutide, marketed under names like Rybelsus, Ozempic, and Wegovy, has been shown to be safe in humans, including those with type 2 diabetes and chronic kidney disease. It is generally well-tolerated and has a good safety profile, with benefits such as weight loss and cardiovascular protection. ^{2 6 7 8 9}

How is the drug Semaglutide unique for treating obesity and kidney disease?

Semaglutide is unique because it is a once-weekly injection that not only helps with weight loss but also improves kidney function by reducing albuminuria (protein in urine) and preserving kidney function, which is particularly beneficial for patients with chronic kidney disease. ^{1 2 3 4 10}

What is the purpose of this trial?

OK-TRANSPLANT 2 is a vanguard study for a large randomized, pragmatic, open-label trial. We will randomize participants with obesity, high-risk CKD/dialysis who are hoping for lose weight for the purpose of kidney transplant. Subjects will either be enrolled on a virtual weight management program or continue their usual care.

Research Team

Kristin K Clemens, MD, MSc

Principal Investigator

St. Joseph's Health Care London

Louise Moist

Principal Investigator

London Health Sciences Centre

Eligibility Criteria

This trial is for individuals with obesity and high-risk chronic kidney disease (CKD) or those on dialysis, aiming to lose weight for a kidney transplant. Participants must be seeking to manage their weight and willing to engage in a virtual program.

Inclusion Criteria

I am at high risk for severe kidney failure or am on dialysis.

BMI > 35 kg/m^2

Exclusion Criteria

I do not have insurance coverage for semaglutide.

I have Type 1 diabetes.

I cannot have a kidney transplant due to health reasons.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vanguard Phase

Feasibility study to ensure recruitment and process inclusivity, and assess program acceptability

12 months

Treatment

Participants receive either usual care or a virtual weight management program with semaglutide and coaching

26 weeks

Virtual coaching once every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Semaglutide
• Virtual Weight Management Coaching

Trial Overview The OK-TRANSPLANT 2 study is testing the effectiveness of virtual weight management coaching compared to usual care practices. Additionally, it will evaluate the use of Semaglutide, a medication that may aid in weight loss.

Participant Groups

Group I: Virtual Weight Management Program Experimental Treatment 2 Interventions

A maximum tolerated dose of semaglutide (Ozempic/Wegovy) will be administered once weekly subcutaneously, up to a dose of 2.0 mg. Participants will also receive nutritional and movement advice, as well as virtual coaching once every 4 weeks for 6 months.

Group II: Usual Care Active Control 1 Intervention

Usual care participants will continue to receive the typical standard of kidney and diabetes care. They will not receive any study medication or coaching.

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?

Western University, Canada

Lead Sponsor

Trials

270

Recruited

62,500+

Lawson Health Research Institute

Collaborator

Trials

684

Recruited

432,000+

Unity Health Toronto

Collaborator

Trials

572

Recruited

470,000+

Queen Elizabeth II Health Sciences Centre

Collaborator

Trials

26

Recruited

14,200+

St. Michael's Hospital (Toronto, Canada)

Collaborator

Trials

1

Recruited

60+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Collaborator

Trials

668

Recruited

424,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Collaborator

Trials

678

Recruited

421,000+

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Collaborator

Trials

686

Recruited

427,000+

Findings from Research

In the STEP 2 trial involving 1,205 participants, semaglutide (both 1.0 mg and 2.4 mg) significantly improved kidney function as measured by urine albumin-to-creatinine ratio (UACR), with reductions of -14.8% and -20.6% respectively, compared to an increase of +18.3% in the placebo group.

Across pooled data from STEP 1-3, semaglutide did not affect estimated glomerular filtration rate (eGFR) decline in participants with normal kidney function, indicating its safety in terms of kidney function preservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Semaglutide on Albuminuria and Kidney Function in People With Overweight or Obesity With or Without Type 2 Diabetes: Exploratory Analysis From the STEP 1, 2, and 3 Trials. Heerspink, HJL., Apperloo, E., Davies, M., et al.[2023]

Subcutaneous semaglutide (Ozempic®), a GLP-1 receptor agonist, has shown significant efficacy in improving glycemic control and reducing HbA1c, albuminuria, and blood pressure in patients with advanced diabetic kidney disease (DKD) during a 6-month follow-up study involving patients on maintenance hemodialysis.

The treatment not only aids in weight loss and appetite suppression but also helps preserve residual kidney function, potentially improving patient outcomes and facilitating their inclusion on kidney transplant waiting lists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Semaglutide, a Glucagon-Like Peptide-1 Receptor Agonist in Real-Life: A Case Series of Patients in Maintenance Incremental Hemodialysis. De la Flor, JC., Lorenzo, JD., Marschall, A., et al.[2022]

Two obese hemodialysis patients successfully lost weight using semaglutide, a GLP-1 receptor agonist, achieving a weight loss of 6.5 to 9.0 kg over 9 months, which is about 1 kg per month.

Semaglutide was well tolerated at a maximum dose of 1 mg/week, suggesting it could be a safe and effective alternative to bariatric surgery for weight management in patients with obesity and kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for treatment of obesity in hemodialysis patients waiting for a kidney transplant: new hope? Touzot, M., Ureña-Torres, P., Dupuy, O.[2022]

In a study involving 486 type 2 diabetes patients, semaglutide was found to be effective in improving glycemic control and achieving weight loss, with no significant differences in efficacy between patients with chronic kidney disease (CKD) and those without.

The treatment was safe for all patients, and CKD severity did not notably affect the treatment response, suggesting that semaglutide can be effectively used in managing type 2 diabetes in patients with varying levels of kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of chronic kidney disease and its severity on the efficacy of semaglutide in type 2 diabetes patients: a multicenter real-world study. García de Lucas, MD., Caballero, I., Fernández-García, JC., et al.[2023]

In a post-hoc analysis of 8416 patients with type 2 diabetes from multiple trials, semaglutide initially caused a decline in estimated glomerular filtration rate (eGFR), but this decline plateaued over time, indicating no long-term adverse effects on kidney function compared to placebo.

Semaglutide significantly reduced urinary albumin-to-creatinine ratio (UACR), suggesting improved kidney health, and there was no increase in kidney-related adverse events compared to other treatments, highlighting its safety and efficacy in managing kidney function in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of once-weekly subcutaneous semaglutide on kidney function and safety in patients with type 2 diabetes: a post-hoc analysis of the SUSTAIN 1-7 randomised controlled trials. Mann, JFE., Hansen, T., Idorn, T., et al.[2020]

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]

Oral semaglutide (Rybelsus®), a GLP-1 receptor agonist, not only helps lower blood sugar levels in people with type 2 diabetes but also promotes significant weight loss and has a lower risk of causing hypoglycemia.

Clinical studies indicate that GLP-1 receptor agonists are safe for individuals with type 2 diabetes and chronic kidney disease, and they may offer additional benefits such as protecting kidney function and reducing the risk of major cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Peptide in a Pill - Oral Semaglutide in the Management of Type 2 Diabetes. Selvarajan, R., Subramanian, R.[2023]

Semaglutide, marketed as Rybelsus, is the first oral glucagon-like peptide receptor agonist approved by the FDA in 2019 for treating type 2 diabetes, highlighting its innovative delivery method.

This medication, taken once daily, aids in glucose control and weight management, potentially leading to improved health outcomes for individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. Blakely, KK., Weaver, K.[2021]

Sodium-glucose cotransporter type 2 (SGLT2) inhibitors provide cardiovascular and renal protection for patients with diabetic kidney disease, but there is still a high residual risk and limited effectiveness in moderate to severe chronic kidney disease (CKD).

Oral semaglutide, a GLP-1 receptor agonist, offers a promising alternative with potent antihyperglycemic effects, low risk of hypoglycemia, and cardiovascular and renal benefits, potentially improving early treatment options for patients with type 2 diabetes and diabetic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide 1(GLP-1) receptor agonists in the management of the patient with type 2diabetes mellitus and chronic kidney disease: an approach for the nephrologist. Cases, A.[2023]

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]

References

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

Effects of Semaglutide on Albuminuria and Kidney Function in People With Overweight or Obesity With or Without Type 2 Diabetes: Exploratory Analysis From the STEP 1, 2, and 3 Trials. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Semaglutide, a Glucagon-Like Peptide-1 Receptor Agonist in Real-Life: A Case Series of Patients in Maintenance Incremental Hemodialysis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Semaglutide for treatment of obesity in hemodialysis patients waiting for a kidney transplant: new hope? [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Influence of chronic kidney disease and its severity on the efficacy of semaglutide in type 2 diabetes patients: a multicenter real-world study. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Effects of once-weekly subcutaneous semaglutide on kidney function and safety in patients with type 2 diabetes: a post-hoc analysis of the SUSTAIN 1-7 randomised controlled trials. [2020]

6. Belgium pubmed.ncbi.nlm.nih.gov

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

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

A Peptide in a Pill - Oral Semaglutide in the Management of Type 2 Diabetes. [2023]

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

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. [2021]

9. Spain pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide 1(GLP-1) receptor agonists in the management of the patient with type 2diabetes mellitus and chronic kidney disease: an approach for the nephrologist. [2023]

10. Belgium pubmed.ncbi.nlm.nih.gov

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