Dapagliflozin for Inflammation

(EFSII Trial)

Recruiting at 1 trial location

Overseen By Stephanie Stilinovic

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Washington University School of Medicine

Must not be taking: SGLT2 inhibitors

Disqualifiers: Cardiac diseases, Type I Diabetes, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

8 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how dapagliflozin affects inflammation in the heart and kidneys. Dapagliflozin belongs to a group of drugs called SGLT2 inhibitors, typically used to lower blood sugar but potentially beneficial for inflammation. Participants will take dapagliflozin for three days to assess its impact on inflammation. Individuals who have never used SGLT2 inhibitors and do not have heart disease or Type 1 diabetes may be suitable for this trial. As an Early Phase 1 trial, this research aims to understand how dapagliflozin works in people, offering participants a chance to contribute to groundbreaking medical knowledge.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial organizers or your doctor.

Is there any evidence suggesting that dapagliflozin is likely to be safe for humans?

Research has shown that dapagliflozin is generally safe, but some risks exist. In studies involving people with type 2 diabetes, dapagliflozin lowered the risk of death from heart problems. However, some side effects, such as ketoacidosis, infections, and sudden kidney problems, have been noted. These side effects are important to consider when deciding to join a trial. The FDA has already approved dapagliflozin for other uses, indicating its safety is well-studied, but discussing potential risks with a healthcare provider is essential. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Dapagliflozin is unique because it targets inflammation by inhibiting a protein called SGLT2, which is primarily known for its role in diabetes treatment. Unlike most anti-inflammatory treatments that directly suppress the immune response, dapagliflozin works by reducing glucose reabsorption in the kidneys, which indirectly modulates inflammation. This novel mechanism could offer a dual benefit by addressing both inflammation and any underlying metabolic issues, making researchers excited about its potential versatility and speed of action.

What evidence suggests that dapagliflozin might be an effective treatment for cardiorenal inflammation?

Research has shown that dapagliflozin can reduce inflammation in the body. One study found that patients who took dapagliflozin for 12 months had lower levels of an important inflammation marker called IL-1B. Dapagliflozin is already known to improve heart health by lowering the risk of heart-related deaths and reducing hospital visits for heart failure. It also helps protect the kidneys by slowing down damage. These findings suggest that dapagliflozin may treat inflammation in both the heart and kidneys, making it a promising treatment to explore further. Participants in this trial will receive dapagliflozin to assess its effects on inflammation. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with inflammation, particularly related to heart and kidney (cardiorenal) issues. Specific eligibility criteria are not provided, so it's best to contact the study organizers for detailed requirements.

Inclusion Criteria

I have never used Sodium-Glucose Co-transporter 2 Inhibitors.

I am a woman not at risk of pregnancy due to sterilization, lack of menstruation for a year, or long-term birth control.

I am willing and able to follow the study's required tests and visits.

Exclusion Criteria

I have been diagnosed with Type 1 Diabetes.

Alcohol use disorder as defined by the NIAAA or use of controlled substances or smoking cigarettes

I often feel dizzy or faint and my blood pressure is below 90.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dapagliflozin 10mg for three days

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dapagliflozin

Trial Overview The trial is studying the effects of a medication called Dapagliflozin, which belongs to a class known as SGLT2 inhibitors, on reducing inflammation in the cardiorenal system.

How Is the Trial Designed?

Group I: Dapagliflozin group Experimental Treatment 1 Intervention

Participants in this arm receive dapagliflozin 10mg for three days.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

In a review of 21 clinical trials involving 5936 patients, dapagliflozin was found to have a low incidence of hypersensitivity adverse events (AEs), with rates similar to those of active or placebo comparators (4.5% vs. 4.3%).

Among Asian patients, dapagliflozin showed an even lower frequency of hypersensitivity AEs compared to comparators (2.0% vs. 4.5%), indicating a potentially safer profile in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypersensitivity Events, Including Potentially Hypersensitivity-Related Skin Events, with Dapagliflozin in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis. Mellander, A., Billger, M., Johnsson, E., et al.[2022]

In a study involving over 34,000 person-years of real-world exposure, dapagliflozin was associated with a significantly lower incidence of hospitalization for acute kidney injury (hAKI) compared to other glucose-lowering drugs, indicating a safer profile for kidney function.

The adjusted incidence rate ratios showed that dapagliflozin users had a 30% reduced risk of hAKI, supporting its safety and efficacy in treating type 2 diabetes mellitus without compromising kidney health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Authorization Safety Study of Hospitalization for Acute Kidney Injury in Patients with Type 2 Diabetes Exposed to Dapagliflozin in a Real-World Setting. Johannes, CB., Beachler, DC., Layton, JB., et al.[2023]

In a study of 210 Type-2 diabetes patients treated with dapagliflozin for at least 12 weeks, significant improvements were observed in fasting blood glucose, hemoglobin A1c, and monocyte high-density lipoprotein ratio, indicating effective glycemic control and reduced inflammation.

The study suggests that the monocyte high-density lipoprotein ratio (MHR) is a useful and cost-effective marker for inflammation in diabetic patients on dapagliflozin, although the neutrophil-leukocyte ratio did not show significant changes and warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of Dapagliflozin on monocyte-HDL ratio and neutrophil-lymphocyte ratio among patients with type-2 diabetes mellitus. Sen Uzeli, Ü., Doğan, M.[2023]

In a study of 50 patients with heart failure and type 2 diabetes, those treated with the SGLT-2 inhibitor empagliflozin showed significant improvements in quality of life and functional capacity after 3 months, as measured by the Minnesota living with heart failure questionnaire and the 6-minute walk test.

Empagliflozin treatment also led to a notable reduction in interleukin-6 levels, suggesting that its anti-inflammatory effects may play a role in the observed benefits for patients with heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin Reduces Interleukin-6 Levels in Patients with Heart Failure. Gotzmann, M., Henk, P., Stervbo, U., et al.[2023]

Dapagliflozin (DAPA), an SGLT2 inhibitor, significantly reduces inflammation in human umbilical vein endothelial cells and macrophages by inhibiting TLR-4 expression and NF-κB activation, regardless of glucose levels.

DAPA promotes a shift from pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages, suggesting its potential to mitigate atherosclerotic complications in diabetes through direct anti-inflammatory mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin exerts anti-inflammatory effects via inhibition of LPS-induced TLR-4 overexpression and NF-κB activation in human endothelial cells and differentiated macrophages. Abdollahi, E., Keyhanfar, F., Delbandi, AA., et al.[2022]

Dapagliflozin is the first selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, which works by regulating renal glucose reabsorption, showing promise in reducing fasting plasma glucose, postprandial plasma glucose, hemoglobin A1c, and body weight in patients with type 2 diabetes.

Clinical safety data from Phase 1 and Phase 2 studies indicate that dapagliflozin is well-tolerated, but further results from ongoing Phase 3 trials are needed to confirm its efficacy and safety across diverse patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin for the treatment of type 2 diabetes. Brooks, AM., Thacker, SM.[2021]

Gliflozins, a class of anti-diabetic drugs, show promise as anti-inflammatory agents for treating inflammatory bowel diseases (IBD), with empagliflozin (EMPA) demonstrating significant effects in both in vitro and in vivo models of intestinal inflammation.

In mouse models, EMPA reduced colonic damage and inflammation, indicating that SGLT-2 inhibitors can alleviate IBD symptoms independently of their blood sugar-lowering effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin attenuates intestinal inflammation through suppression of nitric oxide synthesis and myeloperoxidase activity in in vitro and in vivo models of colitis. Makaro, A., Świerczyński, M., Pokora, K., et al.[2023]

Dapagliflozin effectively lowers blood sugar levels in patients with type 2 diabetes by promoting glucose excretion in urine, leading to a reduction in HbA(1c) levels by approximately 0.5%-1% without increasing the risk of hypoglycemia.

In addition to improving glycemic control, dapagliflozin also contributes to weight loss (around 2-3 kg), making it a promising treatment option that addresses common issues like weight gain and hypoglycemia associated with traditional diabetes medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: an evidence-based review of its potential in the treatment of type-2 diabetes. Chao, EC.[2021]

Dapagliflozin is an effective treatment for type 2 diabetes, showing noninferiority to metformin and glimepiride in clinical trials involving 9 studies, indicating it can be a reliable option for patients.

While generally safe, dapagliflozin is associated with an increased risk of urinary infections and other side effects, suggesting it may be best used as an add-on therapy for patients not adequately controlled on other diabetes medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin for the Treatment of Type 2 Diabetes Mellitus. Aylsworth, A., Dean, Z., VanNorman, C., et al.[2019]

Dapagliflozin, an SGLT2 inhibitor, effectively lowers blood glucose levels by increasing urinary glucose excretion, showing significant reductions in HbA1c and fasting plasma glucose in clinical trials lasting up to 24 weeks.

It is well tolerated with a low incidence of hypoglycemic episodes, although there is a higher risk of genital and urinary tract infections; its efficacy in glycemic control and weight loss is maintained for up to 4 years, making it a valuable option for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dapagliflozin, the first SGLT-2 inhibitor in the treatment of type 2 diabetes]. Albarrán, OG., Ampudia-Blasco, FJ.[2022]

Dapagliflozin, an SGLT2 inhibitor, effectively improves glycemic control in type 2 diabetes and is associated with benefits such as reduced blood pressure, weight loss, and improved lipid profiles.

The review highlights dapagliflozin's potential to lower cardiovascular risks and mitigate microangiopathic complications like kidney disease and retinopathy, emphasizing its underuse in clinical practice despite these benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond the Glycaemic Control of Dapagliflozin: Microangiopathy and Non-classical Complications. Bellido, V., Martínez, J., Calvo, F., et al.[2022]

Dapagliflozin significantly improved blood sugar control in patients with type 2 diabetes who were not adequately managed with metformin and sulfonylurea, with a notable reduction in HbA1c levels and a higher percentage of patients achieving target glycemic response compared to placebo.

The treatment was well tolerated over 24 weeks, although it was associated with increased risks of hypoglycemia and genital infections compared to placebo, indicating the need for monitoring these side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial. Matthaei, S., Bowering, K., Rohwedder, K., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38849829/

Dapagliflozin reduces systemic inflammation in patients with ... Results: Between the baseline and 12-month time point, plasma IL-1B was reduced (- 1.8 pg/mL, P = 0.003) while ketones were increased (0.26 mM, ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1812389

Dapagliflozin and Cardiovascular Outcomes in Type 2 ... With respect to efficacy, dapagliflozin resulted in a lower rate of cardiovascular death or hospitalization for heart failure than placebo (4.9% ...

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

Chronic Kidney Disease | FARXIGA® (dapagliflozin) 5 mg ... The primary efficacy endpoint was a composite of sustained ≥50% eGFR decline, ESKD, or CV or renal death. 97% of patients received a stable dose of ACEi/ARB ...

4. hfsa.org hfsa.org/fda-approves-new-treatment-type-heart-failure

FDA Approves New Treatment For a Type of Heart Failure Farxiga was shown in a clinical trial to improve survival and reduce the need for hospitalization in adults with heart failure with reduced ejection fraction.

5. cardiab.biomedcentral.com cardiab.biomedcentral.com/articles/10.1186/s12933-024-02294-z

Dapagliflozin reduces systemic inflammation in patients with ... In this study, 12-months treatment of dapagliflozin reduced plasma IL-1B level, but not IL6, TNFα or serum hsCRP. To our knowledge, this is the ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S240584402409337X

Safety assessment of dapagliflozin: Real-world adverse ... This study examines the prevalent negative consequences of dapagliflozin, including ketoacidosis, infection, and acute renal injury. This ...

7. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2017/astrazeneca-presents-new-data-underpinning-safety-profile-and-real-world-cv-outcomes-of-farxiga-at-ada-2017-06122017.html

AstraZeneca presents new data underpinning safety profile ... A three-country analysis of nearly 100,000 patients with T2D showed a significant reduction in rates of CV death by 47% (p<0.001) and ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11161924/

Dapagliflozin reduces systemic inflammation in patients ... We hypothesized that dapagliflozin improves cardiac outcomes via beneficial effects on systemic and cardiac inflammation and cardiac fibrosis.

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/202293s026lbl.pdf

FARXIGA (dapagliflozin) - accessdata.fda.gov Serious outcomes have included hospitalization, multiple surgeries, and death. Patients treated with FARXIGA presenting with pain or tenderness, erythema, or ...