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

28 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug for type 2 diabetes with CKD stage 3b-4?

Dapagliflozin, a drug used for type 2 diabetes, has been shown to reduce the risk of kidney disease progression and heart-related issues in people with chronic kidney disease, even if they don't have diabetes. It also helps lower blood sugar levels and has some benefits for heart and kidney health. ^{1 2 3 4 5}

Is dapagliflozin safe for humans?

Dapagliflozin (also known as Farxiga or Forxiga) is generally considered safe for humans, with some studies showing it can reduce the risk of kidney and heart problems in people with chronic kidney disease and type 2 diabetes. However, it may cause mild urinary tract infections and mycotic genital infections, especially in women. ^{2 3 6 7 8}

What makes the drug dapagliflozin unique for treating type 2 diabetes with CKD stage 3b-4?

Dapagliflozin is unique because it not only helps lower blood sugar by preventing glucose reabsorption in the kidneys, but it also offers additional benefits like reducing the risk of kidney disease progression and cardiovascular issues, making it a novel option for patients with chronic kidney disease. ^{1 2 3 4 8}

What is the purpose of this trial?

This is a prospective, observational study to assess the effect of SGLT2 inhibitors on surrogate markers of kidney and cardiovascular health in patients with stage 3b and 4 chronic kidney disease (CKD). This study includes three clinic in person visits and weekly telephone visits for 12 weeks. 1. Recruit 28 patients with CKD stages 3b-4 and follow up for 12 weeks 2. Determine the effect of interventions on the primary outcome variable serum klotho measured by immunoprecipitation-immunoblot

Research Team

Robert Toto, MD

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 (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, 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 (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 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 (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]

References

1. England 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. [2021]

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

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

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

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

4. Spain pubmed.ncbi.nlm.nih.gov

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

5. United States 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. [2021]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. [2021]

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

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. [2021]