Semaglutide for Diabetic Kidney Disease in Type 1 Diabetes

(RT1D Trial)

Recruiting at 3 trial locations

Overseen By Leila Zelnick, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must be taking: Blood pressure drugs, Lipid-lowering drugs

Must not be taking: Pramlintide, Metformin, SGT-2 inhibitors, GLP-1 agonists

Disqualifiers: Type 2 diabetes, Thyroid carcinoma, Pancreatitis, 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: 26 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how semaglutide affects kidney health and blood sugar control in people with type 1 diabetes. Researchers aim to determine if this treatment can improve kidney function and oxygen levels while remaining safe and effective for diabetes management. Participants will receive either semaglutide (a medication for managing blood sugar levels) or a placebo (a harmless pill with no active medicine) to compare results. The trial seeks adults who have had type 1 diabetes for at least 5 years and experience certain kidney-related issues, such as elevated protein levels in their urine. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in diabetes care.

Will I have to stop taking my current medications?

The trial requires that you stay on stable doses of blood pressure and lipid-lowering medications for at least 4 weeks before starting and throughout the trial. Other medications, especially those not approved for type 1 diabetes, may need to be stopped.

Is there any evidence suggesting that semaglutide is likely to be safe for humans?

Research has shown that semaglutide is generally well-tolerated. In one study, fewer participants taking semaglutide experienced serious side effects compared to those on a placebo (49.6% vs. 53.8%). This finding suggests semaglutide might be safer than not taking it. Additionally, semaglutide is already approved for other conditions, which supports its safety profile. While this trial continues to gather more data, current evidence indicates that semaglutide is a safe option for further study in individuals with type 1 diabetes. ^{1 2 3 4 5}

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

Researchers are excited about semaglutide for diabetic kidney disease in Type 1 diabetes because it offers a new approach beyond the standard care of blood pressure control and glucose management. Semaglutide is a GLP-1 receptor agonist, which not only helps in controlling blood sugar levels but also has potential kidney-protective effects by reducing inflammation and oxidative stress in the kidneys. This dual action makes semaglutide particularly promising, as it could slow the progression of kidney damage while simultaneously managing diabetes.

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

Research shows that semaglutide, which participants in this trial may receive, can help improve kidney health. In past studies, semaglutide reduced the risk of kidney problems in people with type 2 diabetes and lowered the chances of heart issues and death from any cause. For people with type 1 diabetes, early research suggests semaglutide might improve kidney function and reduce protein leakage into the urine. These promising results suggest semaglutide might also effectively improve kidney health in type 1 diabetes. ^{1 2 3 4 5}

Who Is on the Research Team?

David Cherney

Principal Investigator

University of Toronto

Irl Hirsch, MD

Principal Investigator

University of Washington

Ian de Boer, MD

Principal Investigator

University of Washington

Jessica Kendrick, MD

Principal Investigator

University of Colorado Anschutz Medical Campus and Children's Hospital Colorado

Katherine Tuttle, MD

Principal Investigator

Providence Healthcare

Are You a Good Fit for This Trial?

This trial is for adults over 18 with type 1 diabetes who have had the condition for at least five years and are showing signs of kidney disease. They must have stable blood pressure and cholesterol medication use, and women able to have children need to use birth control.

Inclusion Criteria

Adequate contraceptive method for females of child-bearing potential

I have been on stable doses of my cholesterol medication for at least 4 weeks.

Persistent urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g, on the most recent two measurements within the prior 3 years

Exclusion Criteria

I have had pancreatitis before.

I have a type of diabetes that is not caused by another condition.

My blood pressure is controlled and not above 160/100 mm Hg.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Real-time continuous glucose monitoring is used to control glycemia prior to randomization

2-4 weeks

Treatment

Participants receive semaglutide or placebo with titration to maximum target dose over 12 weeks

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Semaglutide

Trial Overview The study tests if Semaglutide can improve kidney oxygenation and function in people with type 1 diabetes. It also looks at how it affects blood sugar levels and its overall safety compared to a placebo (a treatment with no active drug).

How Is the Trial Designed?

Group I: Semaglutide Experimental Treatment 1 Intervention

Semaglutide group from 0.25mg to 1.0mg

Group II: Placebo Placebo Group 1 Intervention

Placebo group

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 Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Juvenile Diabetes Research Foundation

Collaborator

Trials

237

Recruited

142,000+

Providence Healthcare

Collaborator

Trials

19

Recruited

3,500+

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

University of Colorado, Denver

Collaborator

Trials

1,842

Recruited

3,028,000+

Published Research Related to This Trial

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]

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]

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]

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]

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 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 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]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2403347

Effects of Semaglutide on Chronic Kidney Disease in ... In this trial, semaglutide reduced the risk of clinically important kidney outcomes, major cardiovascular events, and death from any cause in ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38785209/

Effects of Semaglutide on Chronic Kidney Disease in Patients ... Conclusions: Semaglutide reduced the risk of clinically important kidney outcomes and death from cardiovascular causes in patients with type 2 ...

3. breakthrought1d.org breakthrought1d.org/grants/united-states/washington/randomized-trial-of-semaglutide-for-diabetic-kidney-disease-in-type-1-diabetes/

Randomized trial of semaglutide for diabetic kidney ... The goals of this research are first, to find out if semaglutide improves kidney oxygenation and lowers albuminuria in people with type 1 diabetes, and second, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05822609

NCT05822609 | Trial of Semaglutide for Diabetic Kidney ... The primary objective of this study is to determine the effects of semaglutide on kidney oxygenation and function in type 1 diabetes. The secondary objective is ...

5. diabetesjournals.org diabetesjournals.org/care/article/48/11/1878/163056/Effects-of-Semaglutide-With-or-Without-Concomitant

Effects of Semaglutide With or Without Concomitant ... Semaglutide reduced the risk of the primary kidney outcome by 49% (59 events; hazard ratio [HR] 0.51 [95% CI 0.30, 0.86]) and 21% (682 events; ...