Semaglutide for Polycystic Kidney Disease

Overseen By Diana George

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must be taking: Glucagon-like peptide 1

Must not be taking: Tolvaptan, Weight-affecting drugs

Disqualifiers: Diabetes, Hypertension, Eating disorders, others

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: 12 months

126 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The proposed clinical trial aims to assess if a year of treatment with a glucagon-like peptide 1 receptor agonist, a medication approved for weight management that also improves the body's response to glucose and insulin, can slow kidney growth in adults with autosomal dominant polycystic kidney disease who are overweight or obese. The study will also evaluate changes in abdominal fat and kidney metabolism using cutting-edge images techniques. Blood and urine samples will provide further insight into biological changes that may be linked to the benefits of the intervention, while ensuring careful monitoring of safety and tolerability.

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 regularly use medications that affect weight, appetite, food intake, or energy metabolism.

Is semaglutide safe for humans?

Semaglutide, used under names like Ozempic, Wegovy, and Rybelsus, has been shown to be generally safe in humans, particularly for managing type 2 diabetes and related kidney issues. It is well-tolerated, with benefits like weight loss and cardiovascular protection, and has been tested in large clinical trials with a good safety profile. ^{1 2 3 4 5}

How does the drug semaglutide differ from other treatments for polycystic kidney disease?

Semaglutide is unique because it is a glucagon-like peptide-1 receptor agonist (GLP-1RA) that not only helps control blood sugar levels but also has potential benefits for kidney health, such as reducing inflammation and oxidative stress, which may help preserve kidney function. Unlike other treatments, it is administered once weekly as a subcutaneous injection, offering convenience and potentially improving adherence. ^{1 4 6 7 8}

What data supports the effectiveness of the drug Semaglutide for Polycystic Kidney Disease?

Semaglutide, a drug used for type 2 diabetes, has shown benefits like improved blood sugar control, weight loss, and kidney protection in patients with diabetes-related kidney issues. These effects suggest it might help with kidney function in other conditions, like Polycystic Kidney Disease. ^{1 5 6 9 10}

Are You a Good Fit for This Trial?

Adults aged 18-65 with autosomal dominant polycystic kidney disease (ADPKD), overweight or obese, and a reasonable level of kidney function. Participants should not be in other weight loss programs or clinical studies and must have had a recent ultrasound or MRI.

Inclusion Criteria

ADPKD diagnosis based on the modified Pei-Ravine criteria

Body-mass index of ≥27 kg/m^2

Ability to provide informed consent

Exclusion Criteria

Uncontrolled hypertension (systolic blood pressure > 160 or diastolic blood pressure >100 mm Hg)

I have not been hospitalized or had major surgery in the last 3 months.

Inability to cooperate with or clinical contraindication for MRI including: severe claustrophobia, implants, devices, or non-removable body piercings

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a glucagon-like peptide 1 receptor agonist or placebo for 12 months to assess its efficacy in slowing kidney growth in ADPKD patients

12 months

Weekly visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Semaglutide

Trial Overview The trial is testing Semaglutide, a drug used for weight management that may slow kidney growth in ADPKD patients. It compares the effects of this drug to a placebo over two years, using advanced imaging to monitor changes.

How Is the Trial Designed?

Group I: Tirzepatide Experimental Treatment 1 Intervention

To minimize the risk of gastrointestinal adverse events, we will use a standard dose-escalation regimen for tirzepatide (placebo-matched), starting at 2.5 mg once weekly (OW) at randomization. After 4 weeks of treatment at 2.5 mg, the dose will be escalated to 5 mg OW, which will be maintained for another 4 weeks and then continued as the target dose for 10 months until the end of treatment. As with other nutrient stimulating hormone (NuSH) therapies, dose reductions and extensions of dose-escalation intervals will be permitted if participants experience unacceptable adverse events. The minimum tolerated dose required for continued study participation is 2.5 mg/week. All dose changes will be documented in the study records.

Group II: Placebo Placebo Group 1 Intervention

To minimize the risk of gastrointestinal adverse events, we will use a standard dose-escalation regimen for tirzepatide (placebo-matched), starting at 2.5 mg once weekly (OW) at randomization. After 4 weeks of treatment at 2.5 mg, the dose will be escalated to 5 mg OW, which will be maintained for another 4 weeks and then continued as the target dose for 10 months until the end of treatment. As with other nutrient stimulating hormone (NuSH) therapies, dose reductions and extensions of dose-escalation intervals will be permitted if participants experience unacceptable adverse events. The minimum tolerated dose required for continued study participation is 2.5 mg/week. All dose changes will be documented in the study records.

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?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

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]

In a study involving 56 subjects with varying degrees of renal impairment, semaglutide exposure was found to be similar in those with mild to moderate renal impairment and end-stage renal disease compared to those with normal kidney function, suggesting it is safe for use in these populations.

The drug was well-tolerated overall, with no significant safety concerns or serious adverse events reported, indicating that dose adjustments for semaglutide may not be necessary for patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Tolerability of a Single Dose of Semaglutide, a Human Glucagon-Like Peptide-1 Analog, in Subjects With and Without Renal Impairment. Marbury, TC., Flint, A., Jacobsen, JB., et al.[2018]

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 (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]

Oral semaglutide, a GLP-1 analogue, showed consistent pharmacokinetics across various levels of renal impairment in a trial involving 71 subjects, indicating that kidney function does not significantly affect its absorption or metabolism.

The study found no safety concerns associated with oral semaglutide, and adverse events were similar to those seen with other GLP-1 receptor agonists, suggesting it is safe for use in patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety and Tolerability of Oral Semaglutide in Subjects with Renal Impairment. Granhall, C., Søndergaard, FL., Thomsen, M., et al.[2021]

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]

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]

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]

In a study involving diabetic db/db mice with advanced diabetic kidney disease (DKD), the GLP-1 receptor agonist semaglutide significantly reduced hyperglycemia, hypertension, and albuminuria, while improving kidney health markers such as glomerulosclerosis and podocyte density.

The combination of semaglutide with the ACE inhibitor lisinopril provided additional benefits in managing hypertension and kidney damage, suggesting that semaglutide could be an effective treatment option for patients with DKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nephroprotective Effects of Semaglutide as Mono- and Combination Treatment with Lisinopril in a Mouse Model of Hypertension-Accelerated Diabetic Kidney Disease. Dalbøge, LS., Christensen, M., Madsen, MR., et al.[2022]

Oral semaglutide, a new GLP-1 receptor agonist, significantly reduced glycated hemoglobin (HbA1c) levels by up to 1.4% after 26 weeks compared to placebo, indicating its efficacy in managing blood sugar levels in type 2 diabetes patients.

The treatment also led to greater body weight reductions compared to placebo and sitagliptin, with mild-to-moderate gastrointestinal side effects that typically decreased over time, suggesting it is a safe option with a low risk of severe hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical review of the efficacy and safety of oral semaglutide in patients with type 2 diabetes compared with other oral antihyperglycemic agents and placebo. Lavernia, F., Blonde, L.[2022]

Citations

1. 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]

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

Pharmacokinetics and Tolerability of a Single Dose of Semaglutide, a Human Glucagon-Like Peptide-1 Analog, in Subjects With and Without Renal Impairment. [2018]

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

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

4. Belgium pubmed.ncbi.nlm.nih.gov

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety and Tolerability of Oral Semaglutide in Subjects with Renal Impairment. [2021]

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

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

7. 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]

8. 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]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Nephroprotective Effects of Semaglutide as Mono- and Combination Treatment with Lisinopril in a Mouse Model of Hypertension-Accelerated Diabetic Kidney Disease. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Clinical review of the efficacy and safety of oral semaglutide in patients with type 2 diabetes compared with other oral antihyperglycemic agents and placebo. [2022]