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

Trial Summary

What is the purpose of this trial?

This trial is testing Canagliflozin, a medication that helps remove sugar from the body through urine, on adults with Type 2 diabetes and early kidney disease. The goal is to see if it can protect their kidney function by lowering blood sugar levels.

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 data supports the effectiveness of the drug Canagliflozin for diabetic kidney disease?

Research shows that Canagliflozin can reduce the risk of kidney problems in people with type 2 diabetes by lowering blood sugar levels and promoting weight loss. It has been found to be effective in improving kidney outcomes across different risk categories, as shown in the CANVAS Program study. ^{1 2 3 4 5}

Is canagliflozin safe for humans?

Canagliflozin, used for type 2 diabetes, has been studied for safety and shows some rare but serious side effects like acute pancreatitis and severe ketoacidosis (a dangerous condition with high acid levels in the blood). Common side effects include genital infections and mild urinary tract infections, and caution is advised for elderly patients due to the risk of low blood pressure. ^{1 2 3 6 7}

How is the drug canagliflozin unique for treating diabetic kidney disease?

Canagliflozin is unique because it works by inhibiting a protein in the kidneys called SGLT2, which helps lower blood sugar levels by increasing the amount of sugar excreted in urine. This mechanism is insulin-independent, making it different from many other diabetes treatments, and it also offers potential kidney protection benefits. ^{1 2 3 8 9}

Research Team

Markus Bitzer, MD

Principal Investigator

Professor of Internal Medicine

Eligibility Criteria

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 am between 18 and 80 years old.

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

Exclusion Criteria

Hematuria of unknown etiology

I am allergic to canagliflozin or iodine.

I have had a fracture due to osteoporosis.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 (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 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]

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]

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 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, 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]

References

1. India 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. [2020]

2. Belgium pubmed.ncbi.nlm.nih.gov

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

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

Canagliflozin use in patients with renal impairment-Utility of quantitative clinical pharmacology analyses in dose optimization. [2022]

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

Canagliflozin: first global approval. [2021]

5. United States 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. [2021]

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

Severe Ketoacidosis Associated with Canagliflozin (Invokana): A Safety Concern. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Effects of the SGLT-2 Inhibitor Canagliflozin on Adenine-Induced Chronic Kidney Disease in Rats. [2020]