SGLT2 Inhibitors for Type 2 Diabetes with CKD Stage 3b-4

Overseen By Nancy Wang, Bachelor

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: SGLT2 inhibitors

Disqualifiers: Polycystic kidney disease, Lupus, Transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess how dapagliflozin, an SGLT2 inhibitor, affects kidney and heart health in individuals with both type 2 diabetes and moderate to severe chronic kidney disease (CKD). The researchers seek to understand changes in specific health markers over a 12-week period. Participants will attend three in-person clinic visits and have weekly phone check-ins. Suitable candidates have type 2 diabetes, high blood pressure, and moderate to severe CKD but have not recently used similar medications.

As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants an opportunity to contribute to the development of a promising treatment.

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 must not be using SGLT2 inhibitors before joining. You should also be able to keep a stable dose of any vitamin D and calcium supplements for 180 days after starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that dapagliflozin, a type of medication, is generally safe for people with chronic kidney disease (CKD). In studies, patients taking dapagliflozin had a lower risk of kidney failure and lived longer. These benefits appeared even in those with more advanced CKD, such as stages 3b and 4.

Some patients experienced side effects, but serious issues were rare. The most common side effect was mild urinary tract infections. Overall, evidence suggests that dapagliflozin is safe for people with CKD when monitored by a healthcare professional. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Dapagliflozin is unique because it targets SGLT2 proteins in the kidneys, which helps remove excess glucose from the blood through urine. This mechanism not only aids in controlling blood sugar levels but also offers kidney-protective benefits, making it particularly promising for people with Type 2 Diabetes and chronic kidney disease (CKD). Unlike many standard treatments that primarily focus on blood sugar regulation, dapagliflozin provides dual benefits by also potentially slowing kidney damage progression. Researchers are excited about this treatment because it addresses two significant health issues simultaneously, offering a new approach to improving patient outcomes.

What evidence suggests that this trial's treatments could be effective for Type 2 Diabetes with CKD?

Studies have shown that dapagliflozin, a type of medication, can significantly lower the risk of kidney failure in people with chronic kidney disease (CKD). Research indicates that this treatment slows the progression of kidney disease and can improve survival rates. The US has approved dapagliflozin for treating CKD, demonstrating its effectiveness in managing the condition. In patients with CKD, whether or not they have type 2 diabetes, dapagliflozin has shown benefits for kidney and heart health. This evidence strongly supports its use in patients with CKD stages 3b-4. Participants in this trial will receive dapagliflozin to further evaluate its effects in this population. ^{1 2 5 6 7}

Who Is on the Research Team?

Robert Toto, MD

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with type 2 diabetes and moderate to severe chronic kidney disease (stages 3b-4). Participants should have a history of hypertension, maintain stable doses of vitamin D and calcium supplements, and not be on any SGLT2 inhibitors prior to the study. Exclusions include those with recent immunotherapy or organ transplants, severe liver issues, BMI over 45, active malignancies (except certain skin cancers), or women who are pregnant/breastfeeding and not using contraception.

Inclusion Criteria

Ability of study participant or legally authorized representative to provide informed written consent

I have high blood pressure or I'm on medication to control my normal blood pressure.

I can keep my vitamin D and calcium supplement doses the same for 6 months after starting the trial.

Exclusion Criteria

Inability of the patient, in the opinion of the investigator, to understand and/or comply with procedures and/or follow-up OR any conditions that, in the opinion of the investigator, may render the patient unable to complete the study. Patients who cannot complete the patient reported outcome (PRO) assessments can still participate in the study

I haven't had treatments like chemotherapy or immunotherapy for kidney disease in the last 6 months.

I have been on SGLT2 inhibitor medication or had a bad reaction to it within the last 8 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Baseline visit where participants start taking prescribed SGLT2i

1 day

1 visit (in-person)

Treatment

Participants receive SGLT2 inhibitors and are monitored for changes in cardiovascular and kidney biomarkers

12 weeks

3 visits (in-person), weekly telephone visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dapagliflozin
• EffCaMgCitrate 480 mg
• Placebo Dapagliflozin
• Placebo EffCaMgCitrate

Trial Overview The trial is observing how SGLT2 inhibitors affect heart and kidney health markers in patients with stage 3b-4 chronic kidney disease over a period of 12 weeks. It involves three clinic visits and weekly phone calls. The main focus is on changes in serum klotho levels—a protein linked to aging—measured by specific lab techniques.

How Is the Trial Designed?

Group I: Group 1 Experimental Treatment 1 Intervention

Group 1: take prescribed SGLT2i after baseline visit.

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

Approved in European Union as Forxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Approved in United States as Farxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Approved in Canada as Farxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

Dapagliflozin (Farxiga) is approved for reducing the risk of declining kidney function and kidney failure in adults with chronic kidney disease, regardless of whether they have type 2 diabetes.

It also helps lower the risk of cardiovascular death and hospitalization for heart failure, highlighting its efficacy in managing both kidney and heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. Aschenbrenner, DS.[2023]

Dapagliflozin is an effective treatment for type 2 diabetes, proven through multiple controlled clinical trials that assess its efficacy, safety, and tolerability.

It is approved by the FDA for use as a standalone therapy or in combination with other glucose-lowering medications, including insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. Davis, PN., Ndefo, UA., Oliver, A.[2021]

Dapagliflozin effectively lowers blood sugar levels and glycated hemoglobin (HbA1c) in patients with type 2 diabetes, with a low risk of hypoglycemia and additional benefits like weight loss and reduced blood pressure.

While it is generally safe, dapagliflozin can increase the risk of genital infections, particularly in women, and its efficacy may be reduced in patients with kidney issues; ongoing trials are investigating its potential cardiovascular and renal protective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dapagliflozin (forxiga®) : SGLT 2 cotransporter inhibitor as glucose-lowering agent in type 2 diabetes]. Scheen, AJ.[2021]

Dapagliflozin (Forxiga) is no longer authorized for the treatment of type 1 diabetes mellitus, indicating a significant change in its regulatory status.

This decision reflects safety concerns or efficacy issues that may have arisen from clinical evaluations or post-marketing surveillance, emphasizing the importance of ongoing drug safety assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin no longer licensed for type 1 diabetes. [2022]

Dapagliflozin, an SGLT2 inhibitor, is effective in treating type 2 diabetes and has been shown to significantly reduce cardiovascular and major renal events in clinical trials.

In the DAPA-CKD trial, dapagliflozin notably decreased the risk of kidney disease progression in patients with chronic kidney disease, making it a valuable treatment option for both diabetic and non-diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on dapagliflozin for chronic kidney disease. Kelly, MS.[2022]

Dapagliflozin, an SGLT2 inhibitor, effectively reduces blood sugar levels in type 2 diabetes by increasing urinary glucose excretion, with a pharmacokinetic profile similar to previous studies in non-Chinese subjects.

The drug was well tolerated in a study of 14 healthy Chinese participants, with minimal accumulation after multiple doses and a low incidence of adverse effects, supporting its use at the recommended dose of 10 mg daily.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic properties of single- and multiple-dose of dapagliflozin, a selective inhibitor of SGLT2, in healthy Chinese subjects. Yang, L., Li, H., Li, H., et al.[2021]

Dapagliflozin 10 mg significantly reduced HbA1c levels, body weight, fasting plasma glucose, and systolic blood pressure in patients with type 2 diabetes and moderate renal impairment over 24 weeks, compared to placebo.

The treatment was well-tolerated, with no significant increase in adverse events, and any decrease in kidney function (eGFR) returned to baseline levels shortly after stopping the medication, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dapagliflozin in patients with type 2 diabetes and moderate renal impairment (chronic kidney disease stage 3A): The DERIVE Study. Fioretto, P., Del Prato, S., Buse, JB., et al.[2021]

Dapagliflozin (DAPA) is an effective SGLT2 inhibitor for treating type 2 diabetes, showing favorable pharmacokinetics and pharmacodynamics that help lower blood sugar levels while having beneficial effects on other metabolic risk factors.

While DAPA is generally safe, it carries an increased risk of genital and urinary infections, and concerns about bladder cancer and cardiovascular safety remain, prompting the FDA to seek further data on these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. Maranghi, M., Carnovale, A., Durante, C., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8729835/

Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease The sodium-glucose cotransporter 2 inhibitor dapagliflozin significantly reduced risk of kidney failure and prolonged survival in patients with CKD with or ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2024816

Dapagliflozin in Patients with Chronic Kidney Disease The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known.

3. astrazeneca.com astrazeneca.com/media-centre/press-releases/2021/farxiga-approved-in-the-us-for-ckd.html

Farxiga approved in the US for the treatment of chronic ... We've shown impressive efficacy for Farxiga in type-2 diabetes, heart failure with reduced ejection fraction and, most recently, chronic kidney ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38730538/

The long-term effects of dapagliflozin in chronic kidney ... Treatment with dapagliflozin delayed time to first event for kidney failure, all-cause mortality, sustained decline in kidney function and hospitalization for ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03036150

A Study to Evaluate the Effect of Dapagliflozin on Renal ... The purpose of this study is to evaluate the effect of dapagliflozin on renal outcomes and cardiovascular mortality in patients with chronic kidney disease.

6. astrazeneca.com astrazeneca.com/media-centre/medical-releases/new-sub-analyses-further-support-consistency-of-farxigas-cardiorenal-and-mortality-benefits-in-treating-chronic-kidney-disease.html

New sub-analyses further support consistency of Farxiga's ... DAPA-CKD Phase III trial sub-analyses showed that kidney and cardiovascular outcomes were consistent regardless of geographic region or use of ...

7. farxiga.com farxiga.com/type-2-diabetes/ckd-t2d-connection

CKD And Type 2 Diabetes | FARXIGA® (dapagliflozin) For adults with type 2 diabetes, FARXIGA reduces the risk of hospitalization for heart failure in those with heart disease or risk factors for it.