Dapagliflozin for Type 2 Diabetes

(Hyper Trial)

No longer recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: The University of Texas Health Science Center at San Antonio

Must not be taking: Diuretics, Steroids, Beta blockers

Disqualifiers: Heart failure, Cancer, Liver disease, 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

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: 5

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess how the drug dapagliflozin (also known as Farxiga, Forxiga, Xigduo XR, Qtern, Qternmet XR) affects kidney health in individuals with type 2 diabetes who have high kidney filtration rates. It compares dapagliflozin to metformin, a common diabetes medication, to evaluate their effects on kidneys. Individuals newly diagnosed with type 2 diabetes, who are not yet on medication and have specific kidney filtration rates, might be suitable candidates for this study. Participants will engage in the study for approximately 16 weeks. As a Phase 4 trial, this study involves an FDA-approved treatment and aims to further understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial requires that participants do not take medications that interfere with the renin-angiotensin system or renal function, including diuretics, steroids, beta blockers, alpha blockers, and antiobesity drugs. If you are taking any of these, you may need to stop them to participate.

What is the safety track record for these treatments?

Research has shown that dapagliflozin, the treatment tested in this trial, has a well-understood safety record from past studies. In studies with adults, no cases of diabetic ketoacidosis (a serious diabetes complication) appeared in patients with or without type 2 diabetes. However, reports have indicated sudden kidney injury in people with type 2 diabetes taking dapagliflozin, especially if they are at risk of dehydration.

When starting dapagliflozin, individuals might experience a small drop in kidney function, measured by eGFR, which assesses kidney performance. This drop does not appear to lead to long-term kidney problems.

These findings suggest that while dapagliflozin is generally safe, some risks, particularly concerning kidney health, should be considered. Always consult a healthcare provider about any concerns or questions before starting a new treatment. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about dapagliflozin for treating type 2 diabetes-related kidney issues because it offers a unique approach compared to traditional treatments like metformin and sulfonylureas. Unlike these standard options, which mainly lower blood sugar, dapagliflozin is an SGLT2 inhibitor that reduces glucose reabsorption in the kidneys, leading to lower blood sugar levels and potential protective effects on kidney function. This novel mechanism not only helps manage blood sugar but also addresses kidney hyperfiltration, a common issue in diabetic patients. Additionally, dapagliflozin could offer a dual benefit of improving both blood sugar control and kidney health, making it a promising option for comprehensive diabetes management.

What evidence suggests that this trial's treatments could be effective for hyperfiltering T2DM patients?

Research has shown that dapagliflozin, one of the treatments in this trial, can improve kidney function in people with type 2 diabetes. One study found that dapagliflozin significantly lowered the rate at which the kidneys filter blood, often too high in these patients. Another study discovered that dapagliflozin reduced protein in the urine, indicating better kidney health. Additionally, research highlighted that dapagliflozin was more effective at normalizing overactive kidney function than a combination of metformin and glipizide, which are also being studied in separate arms of this trial. These findings suggest that dapagliflozin effectively protects kidney function in patients with diabetes. ^{3 6 7 8 9}

Who Is on the Research Team?

Ralph DeFronzo, MD

Principal Investigator

The University of Texas Health Science Center at San Antonio

Are You a Good Fit for This Trial?

Inclusion Criteria

Your body mass index (BMI) falls between 20 and 45 kg/m2.

HbA1c = 7.5% to 12%

Hematocrit >34% --BP < 145/90 mmHg

Exclusion Criteria

You have had cancer or a serious disease affecting your major organs in the past.

You have moderate to severe heart failure.

You are currently taking steroids, beta blockers, alpha blockers, or antiobesity drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are treated with dapagliflozin or metformin for 4 months to assess changes in renal function and size

16 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dapagliflozin
• Glipizide 5 MG
• Metformin

How Is the Trial Designed?

Group I: Dapagliflozin/Normofiltration Experimental Treatment 1 Intervention

Subjects with eGFR below 124 ml/min per 1.73 m2 will be randomized to dapagliflozin, 5 mg/day. After 2 weeks (Visit 5), dapagliflozin will be increased to 10 mg/day, Subjects who are taking Metformin at time of randomization will have add Dapagliflozin added to current metformin.

Group II: Dapagliflozin/Hyperfiltration Experimental Treatment 1 Intervention

Subjects with eGFR above 125 ml/min per 1.73 m2 will be randomized to dapagliflozin, 5 mg/day. After 2 weeks (Visit 5), dapagliflozin will be increased to 10 mg/day, Subjects who are taking Metformin at time of randomization will have Dapagliflozin added to current metformin.

Group III: Metformin/Hyperfiltration Active Control 2 Interventions

Subjects who Drug naïve we will give Metformin- XR, 1000 mg/day. After 2 weeks (Visit 5), metformin will be increased to 1000 mg bid (twice a day).Subject who are on metformin at time of randomization we will add Glipizide 5 mg( to be increased to 10 mg at Visit 5), Subject who are on Glipizide at time of randomization will have Metformin- XR, 1000 mg/day added. After 2 weeks (Visit 5), metformin will be increased to 1000 mg bid (twice a day).

Group IV: Metformin/Normofiltration Active Control 2 Interventions

Subjects with eGFR below 124 ml/min per 1.73m2 drug naïve will receive Metformin- XR, 1000 mg/day. After 2 weeks (Visit 5), metformin will be increased to 1000 mg bid (twice a day).Subject who are on metformin at time of randomization we will add Glipizide 5 mg( to be increased to 10 mg at Visit 5), Subject who are on Glipizide at time of randomization we will add Metformin- XR, 1000 mg/day. After 2 weeks (Visit 5), metformin will be increased to 1000 mg bid (twice a day).

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?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

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 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 (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 (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]

Dapagliflozin is an effective SGLT2 inhibitor for managing type 2 diabetes, showing consistent reductions in blood glucose levels and body weight over long-term follow-up periods of 1-4 years across various clinical trials.

It has a low risk of causing hypoglycemia and is generally well tolerated, although it can lead to genital infections, particularly in women, and is not recommended for patients with moderate to severe renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: a review of its use in patients with type 2 diabetes. Plosker, GL.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02911792?term=dapagliflozin%20AND%20metformin&rank=2&tab=results

Effect of Farxiga on Renal Function and Size in Type 2 ... Subjects with eGFR equal or above 125 ml/min/1.73m2 will be randomized to dapagliflozin, 5 mg/day. After 2 weeks (Visit 5), dapagliflozin will be increased ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9813108/

Effect of dapagliflozin on the initial estimated glomerular ... The EMPA-REG outcome trial has clearly demonstrated that empagliflozin reduced the risk of worsening kidney injury in patients with type 2 DM (progression to ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0928098725000442

Dapagliflozin in diabetic kidney disease patients with ... Results. The mean eGFR change at 2 weeks in the hyperfiltration with SBP > 120 mmHg group was greater than in the non-hyperfiltration with SBP ≤ ...

4. kireports.org kireports.org/article/S2468-0249(25)00464-4/fulltext

Randomized Trial of Dapagliflozin in Patients With ... At 6 weeks, dapagliflozin significantly decreased GFR by 1.88 ± 5.00 ml/min per 1.73 m2 (P = 0.022) and proteinuria by 0.50 (−0.10 to 0.80) g/24 h (P = 0.026) ...

5. diabetesjournals.org diabetesjournals.org/diabetes/article/72/Supplement_1/887-P/150007/887-P-Renal-Benefit-of-Dapagliflozin-Therapy-in

887-P: Renal Benefit of Dapagliflozin Therapy in Hyperfiltering ... Conclusion These results indicate that dapagliflozin, but not metformin+glipizide therapy, normalizes glomerular hyperfiltration and reduces ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/202293s031lbl.pdf

FARXIGA® (dapagliflozin) tablets, for oral use The safety profile observed in the placebo-controlled trial in pediatric patients with type 2 diabetes mellitus was similar to that observed in adults [see ...

7. farxiga-hcp.com farxiga-hcp.com/chronic-kidney-disease

Chronic Kidney Disease | FARXIGA® (dapagliflozin) 5 mg ... Proven Safety Profile in a Broad Range of Adults With CKD · NO occurrences of diabetic ketoacidosis were observed with FARXIGA in adults with or without T2D in ...

8. farxiga.com farxiga.com/kidney-numbers

Kidney Numbers | FARXIGA® (dapagliflozin) There have been reports of sudden kidney injury in people with type 2 diabetes who are taking FARXIGA. You may be at a higher risk of dehydration if you take ...

9. renalandurologynews.com renalandurologynews.com/news/egfr-dip-with-dapagliflozin-not-linked-to-higher-ckd-progression-risk/

eGFR Dip With Dapagliflozin Not Linked to Higher CKD ... A modest acute dip in estimated glomerular filtration rate (eGFR) within 2 weeks of dapagliflozin initiation does not increase progression risk in patients ...