Canagliflozin for Diabetic Kidney Disease

Overseen By Chrysta C Lienczewski, BS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Michigan

Must be taking: RAAS inhibitors, GLP-1 agonists

Must not be taking: Steroids, Immunosuppressants, Investigational drugs

Disqualifiers: Liver disorders, Cardiovascular disease, Cancer, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 6 months

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Canagliflozin, an already approved medication, can protect kidney function in people with Type 2 diabetes. Participants will take this medication and undergo various tests to assess its benefits for their kidneys. Individuals with Type 2 diabetes for at least three years, without severe kidney issues or other major health problems, might be suitable candidates. The study includes regular check-ups and tests, such as blood and urine samples, to monitor kidney health closely. As a Phase 4 trial, it aims to understand how this FDA-approved treatment can benefit more patients.

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 currently using steroids, immunosuppressants, or certain other drugs. If you are on a RAAS inhibitor or GLP-1 receptor agonist, you must have been on it for at least 3 months before starting the trial.

What is the safety track record for Canagliflozin?

Research has shown that Canagliflozin, a medication for Type 2 diabetes, is generally safe. Studies have found that it can lower the risk of serious kidney and heart problems. Specifically, people taking Canagliflozin experienced fewer cases of kidney failure and heart issues compared to those on a placebo over about 2.6 years.

Other research indicates that Canagliflozin reduced the risk of major kidney problems by about 30%. This means that individuals on Canagliflozin were less likely to reach end-stage kidney disease or experience a significant drop in kidney function.

Overall, Canagliflozin has been well-tolerated by people with diabetes, with no major safety concerns reported. This suggests that the treatment is safe, especially for those with diabetic kidney disease. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Canagliflozin is unique because it targets diabetic kidney disease by inhibiting the SGLT2 protein in the kidneys, which helps lower blood sugar and protect kidney function simultaneously. Unlike traditional treatments that primarily focus on controlling blood sugar through insulin or other glucose-lowering medications, Canagliflozin offers the added benefit of potentially slowing down kidney damage. Researchers are excited about this treatment because it represents a dual-action approach that not only manages diabetes but also directly addresses the progressive nature of kidney disease in diabetic patients.

What is the effectiveness track record for Canagliflozin in protecting kidney function in Type 2 diabetes?

Research has shown that Canagliflozin, a medication for people with Type 2 diabetes, can help protect the kidneys. One study found that people taking Canagliflozin had a lower risk of kidney failure compared to those taking a placebo, which contains no active medicine. Specifically, the chance of serious kidney problems was about 30% lower for those on the drug. It also reduced the need for dialysis or kidney transplants and lowered the risk of death from kidney-related issues. Overall, Canagliflozin has been effective in supporting kidney health in people with Type 2 diabetes. Participants in this trial will receive Canagliflozin as part of the SGLT2i Arm to further evaluate its benefits for diabetic kidney disease. ^{2 3 6 7 8}

Who Is on the Research Team?

Markus Bitzer, MD

Principal Investigator

Professor of Internal Medicine

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with Type 2 diabetes diagnosed at least 3 years ago, who may also have kidney disease. Participants must have two functioning kidneys confirmed by ultrasound and be willing to undergo multiple tests including MRIs, biopsies, and provide blood, urine, and optional stool samples.

Inclusion Criteria

I am willing to join the study after understanding its details.

I have been diagnosed with type 2 diabetes for 3 years or more.

Screening urinary albumin-to-creatinine ratio <3000 mg/g

Exclusion Criteria

Hematuria of unknown etiology

I am allergic to canagliflozin or iodine.

Conditions likely to interfere with informed consent or compliance with the protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive 100 mg of canagliflozin daily for six months, with kidney MRI and biopsy at study entry and follow-up visits

6 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with annual follow-up until death or development of end-stage kidney disease

Annually

What Are the Treatments Tested in This Trial?

Interventions

• Canagliflozin

Trial Overview The study is testing the effects of an FDA-approved SGLT2 inhibitor drug called Canagliflozin (INVOKANA) on kidney function in people with Type 2 diabetes. It's an open-label trial where participants know they're taking Canagliflozin daily for six months while undergoing health assessments.

How Is the Trial Designed?

Group I: SGLT2i Arm Experimental Treatment 1 Intervention

Canagliflozin is already approved in European Union, United States for the following indications:

Approved in European Union as Invokana for:

• Type 2 diabetes mellitus
• Cardiovascular risk reduction

Approved in United States as Invokana for:

• Type 2 diabetes mellitus
• Cardiovascular risk reduction
• Diabetic kidney disease

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

University of Colorado, Denver

Collaborator

Trials

1,842

Recruited

3,028,000+

Renal Pre-Competitive Consortium (RPC3)

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

Canagliflozin is effective in improving glycemic control in adults with type 2 diabetes, specifically by inhibiting SGLT2 to increase urinary glucose excretion, with a focus on patients having a baseline eGFR of 45 mL/min/1.73 m² or higher.

The safety analyses conducted during the clinical development of canagliflozin provided a comprehensive understanding of its impact on renal function, allowing for informed dosing recommendations in patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Canagliflozin use in patients with renal impairment-Utility of quantitative clinical pharmacology analyses in dose optimization. Khurana, M., Vaidyanathan, J., Marathe, A., et al.[2022]

Canagliflozin significantly improved glycemic control in patients with type 2 diabetes and stage 3 chronic kidney disease, reducing HbA1c levels compared to placebo after 26 weeks.

The treatment was generally well tolerated, with similar rates of adverse events compared to placebo, although there were slightly higher instances of urinary tract infections and other osmotic diuresis-related effects at the higher dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Yale, JF., Bakris, G., Cariou, B., et al.[2022]

Canagliflozin, a sodium-glucose co-transporter 2 inhibitor for type 2 diabetes, can cause acute pancreatitis, a very rare side effect occurring in less than 1% of patients, as demonstrated in a case of a 50-year-old male who developed diabetic ketoacidosis after 4 days of treatment.

The case highlights the importance of monitoring for serious side effects like acute pancreatitis when prescribing canagliflozin, emphasizing the need for more detailed guidelines on patient selection for this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute pancreatitis in the use of canagliflozin: A rare side-effect of the novel therapy for type 2 diabetes mellitus. Srivali, N., Thongprayoon, C., Cheungpasitporn, W., et al.[2020]

Canagliflozin, an SGLT2 inhibitor, effectively lowers blood sugar levels and HbA1c by promoting glucose excretion in urine, with an average HbA1c reduction of 0.75% when used alongside other diabetes treatments.

While canagliflozin is generally safe, it can cause genital infections and urinary tract infections, and caution is advised for elderly patients and those with renal insufficiency, as its efficacy decreases with lower kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Canagliflozin (Invokana): kidney SGLT2 cotransporter inhibitor for treating type 2 diabetes]. Scheen, AJ.[2018]

Canagliflozin, an SGLT-2 inhibitor, showed potential in improving kidney function in rats with non-diabetic chronic kidney disease (CKD) induced by adenine, significantly reducing inflammation and oxidative stress markers.

The drug did not cause any significant adverse effects, suggesting it may be safe for further investigation in human trials for CKD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the SGLT-2 Inhibitor Canagliflozin on Adenine-Induced Chronic Kidney Disease in Rats. Ali, BH., Al Salam, S., Al Suleimani, Y., et al.[2020]

In a large retrospective cohort study involving over 55,000 patients with type 2 diabetes, canagliflozin was associated with a significantly lower risk of hospital admission for heart failure compared to DPP-4 inhibitors, GLP-1 receptor agonists, and sulfonylureas.

Canagliflozin showed similar risks for major cardiovascular events (like heart attacks and strokes) when compared to these other diabetes medications, indicating its safety profile in terms of cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study. Patorno, E., Goldfine, AB., Schneeweiss, S., et al.[2022]

Canagliflozin (Invokana™) is the first SGLT2 inhibitor approved in the USA for treating type 2 diabetes, working by blocking glucose reabsorption in the kidneys, which lowers blood glucose levels independently of insulin.

By increasing urinary glucose excretion, canagliflozin may also help reduce body weight, making it a potentially beneficial option for managing diabetes and associated weight issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Canagliflozin: first global approval. Elkinson, S., Scott, LJ.[2021]

Canagliflozin, an SGLT-2 inhibitor introduced for type 2 diabetes, shows potential for type 1 diabetes treatment due to its insulin-independent mechanism of action.

However, it carries serious risks, including severe metabolic acidosis and euglycemic diabetic ketoacidosis, which require immediate recognition and treatment to prevent life-threatening complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe Ketoacidosis Associated with Canagliflozin (Invokana): A Safety Concern. Gelaye, A., Haidar, A., Kassab, C., et al.[2022]

Canagliflozin significantly reduces the risk of cardiovascular events and kidney outcomes in individuals with type 2 diabetes, showing a consistent relative effect across different KDIGO risk categories based on kidney function and albumin levels.

Higher KDIGO risk categories experienced greater absolute reductions in cardiovascular outcomes, suggesting that patients with more severe kidney disease may benefit more from canagliflozin treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative and Absolute Risk Reductions in Cardiovascular and Kidney Outcomes With Canagliflozin Across KDIGO Risk Categories: Findings From the CANVAS Program. Neuen, BL., Ohkuma, T., Neal, B., et al.[2021]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1811744

Canagliflozin and Renal Outcomes in Type 2 Diabetes and ... The risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30990260/

Canagliflozin and Renal Outcomes in Type 2 Diabetes and ... The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02065791

NCT02065791 | Evaluation of the Effects of Canagliflozin ... The goal of this study is to assess whether canagliflozin has a renal and vascular protective effect in reducing the progression of renal impairment ...

4. invokanahcp.com invokanahcp.com/dkd-benefit/

DKD Benefit | INVOKANA® (canagliflozin) HCP INVOKANA® reduced the relative risk of the primary composite outcome of end-stage kidney disease, doubling of serum creatinine, and renal or CV death.

5. yoda.yale.edu yoda.yale.edu/clinical-trial/nct02065791-a-randomized-double-blind-event-driven-placebo-controlled-multicenter-study-of-the-effects-of-canagliflozin-on-renal-and-cardiovascular-outcomes-in-subjects-with-type-2-diabetes-mell/

NCT02065791 - The YODA Project A Randomized, Double-blind, Event-driven, Placebo-controlled, Multicenter Study of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Subjects ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7217416/

Renal, Cardiovascular, and Safety Outcomes of Canagliflozin ... Canagliflozin safely prevents clinically important renal and cardiovascular events in people with diabetes, substantial albuminuria, and an eGFR at commencement ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7261301/

Canagliflozin for the Treatment of Diabetic Kidney Disease ... Canagliflozin treatment was associated with a 30% relative risk reduction of the primary composite outcome of ESKD, doubling of serum creatinine ...

8. diabetesjournals.org diabetesjournals.org/care/article/47/3/501/154163/Impact-of-Canagliflozin-on-Kidney-and

Impact of Canagliflozin on Kidney and Cardiovascular ... Canagliflozin demonstrated CV and kidney benefits, including a reduction in CKD progression regardless of diabetes duration. These findings may ...