Semaglutide for Diabetic Kidney Disease in Type 1 Diabetes

(RT1D Trial)

Recruiting at 3 trial locations

Overseen By Ernest Ayers, MSPH

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

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 to determine the glycemic effects and safety of semaglutide in type 1 diabetes.

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.

What data supports the effectiveness of the drug semaglutide for diabetic kidney disease in type 1 diabetes?

Semaglutide, a drug used for type 2 diabetes, has shown benefits like better blood sugar control, weight loss, and kidney protection in patients with kidney disease. These effects suggest it might help people with type 1 diabetes and kidney issues too. ^{1 2 3 4 5}

Is semaglutide safe for humans?

Semaglutide, used under names like Ozempic, Wegovy, and Rybelsus, has been shown to be generally safe in humans, with studies indicating it is well-tolerated and has a good safety profile, especially in people with type 2 diabetes and chronic kidney disease. ^{1 2 3 4 6}

How is the drug semaglutide unique for treating diabetic kidney disease in type 1 diabetes?

Semaglutide is unique because it is a glucagon-like peptide-1 receptor agonist (GLP-1RA) that not only improves blood sugar control but also offers additional benefits like reducing blood pressure, inflammation, and weight, which are important for kidney health. It is administered once weekly as a subcutaneous injection, making it convenient for patients, and it has shown potential in preserving kidney function, which is crucial for those with diabetic kidney disease. ^{1 3 4 7 8}

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

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Placebo (Other)
• Semaglutide (Glucagon-like peptide-1 (GLP-1) receptor agonist)

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).

Participant Groups

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 Canada, Japan for the following indications:

Approved in Canada as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Japan as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

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+

Findings from Research

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]

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]

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]

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 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®) 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 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]

References

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

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

3. 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]

4. 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]

5. 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]

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

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

7. 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]

8. 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]