Dapagliflozin for Inflammation

(EFSII Trial)

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

Trial Summary

What is the purpose of this trial?

The research aims to understand how a specific type of medication called Sodium-glucose co-transporter 2 (SGLT2) inhibitors affect cardiorenal inflammation.

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.

What data supports the effectiveness of the drug Dapagliflozin for inflammation?

Dapagliflozin, a drug used for type 2 diabetes, heart failure, and kidney disease, has shown benefits like reducing blood pressure and weight, which can help with inflammation-related conditions. Additionally, similar drugs like empagliflozin have been found to lower inflammation markers in heart failure patients, suggesting potential anti-inflammatory effects of SGLT-2 inhibitors like dapagliflozin. ^{1 2 3 4 5}

Is dapagliflozin generally safe for humans?

Dapagliflozin, used for type 2 diabetes, has been studied for safety, showing some risks like hypersensitivity (allergic reactions) and potential kidney issues. However, it generally does not increase the risk of low blood sugar or weight gain, and ongoing studies continue to monitor its safety. ^{6 7 8 9 10}

How does the drug dapagliflozin differ from other treatments for inflammation?

Dapagliflozin is unique because it not only helps control blood sugar levels in diabetes but also has direct anti-inflammatory effects by inhibiting specific pathways (TLR-4 and NF-κB) involved in inflammation. This dual action makes it different from other treatments that typically focus only on reducing inflammation or managing blood sugar separately. ^{2 5 6 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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 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]

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 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]

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]

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 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 (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]

References

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

Beyond the Glycaemic Control of Dapagliflozin: Microangiopathy and Non-classical Complications. [2022]

2. Spain pubmed.ncbi.nlm.nih.gov

[Dapagliflozin, the first SGLT-2 inhibitor in the treatment of type 2 diabetes]. [2022]

3. United States 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. [2022]

4. Italy pubmed.ncbi.nlm.nih.gov

The effects of Dapagliflozin on monocyte-HDL ratio and neutrophil-lymphocyte ratio among patients with type-2 diabetes mellitus. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Empagliflozin Reduces Interleukin-6 Levels in Patients with Heart Failure. [2023]

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

Dapagliflozin for the Treatment of Type 2 Diabetes Mellitus. [2019]

7. New Zealand 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. [2022]

8. New Zealand 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. [2023]

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

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

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

Dapagliflozin for the treatment of type 2 diabetes. [2021]

11. Switzerland 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. [2023]

12. Netherlands 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. [2022]