SGLT2 Inhibition for High-Risk Prostate Cancer

Overseen By Melissa A Reimers, M.D.

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Washington University School of Medicine

Must not be taking: SGLT2i, Thiazolidinedione, Systemic steroids, others

Disqualifiers: Stroke, Type 1 diabetes, Severe kidney disease, others

Stay on Your Current Meds

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing if dapagliflozin, a diabetes drug, is safe and well-tolerated for patients with advanced prostate cancer. The medication helps lower blood sugar by making the kidneys remove it through urine.

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 cannot participate if you are currently using SGLT2 inhibitors, thiazolidinediones, or regularly scheduled systemic steroids like prednisone or dexamethasone.

What data supports the effectiveness of the drug Dapagliflozin for high-risk prostate cancer?

There is no direct evidence from the provided research that supports the effectiveness of Dapagliflozin specifically for high-risk prostate cancer. However, some studies suggest that diabetes and its management can influence prostate cancer progression, which may imply potential indirect effects of antidiabetic drugs like Dapagliflozin on prostate cancer. ^{1 2 3 4 5}

Is dapagliflozin generally safe for humans?

Dapagliflozin, used for type 2 diabetes, is generally well tolerated with a low risk of low blood sugar, but it can cause genital infections, especially in women, and mild urinary tract infections. It is not recommended for people with moderate or severe kidney problems. ^{6 7 8 9 10}

How does the drug SGLT2 inhibitor differ from other treatments for high-risk prostate cancer?

SGLT2 inhibitors are unique because they work by increasing the excretion of glucose through urine, which is independent of insulin, and they have shown cardiorenal protective effects. While primarily used for diabetes, their novel mechanism and potential benefits in other conditions like high-risk prostate cancer are being explored, setting them apart from traditional cancer treatments. ^{11 12 13 14 15}

Research Team

Melissa A Reimers, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

Men over 18 with high-risk or very high risk localized prostate cancer, who are planning a radical prostatectomy and can undergo an MRI. They must have normal organ function and controlled type 2 diabetes (if diabetic). Exclusions include insulin-requiring diabetes, recent strokes, other active cancers, severe illnesses that could interfere with the study, or past use of certain diabetes drugs.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

My prostate cancer is classified as high or very high risk.

My prostate cancer is considered very high risk based on its stage or specific features.

Exclusion Criteria

You are currently taking any experimental drugs for other studies.

HbA1c > 10%, unless approved by endocrinologist.

I do not have any implants that would interfere with an MRI of my prostate.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dapagliflozin at 10 mg by mouth once daily for 4 weeks prior to prostatectomy

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• BIOSENSE Meter (Device)
• Dapagliflozin (SGLT2 Inhibitor)

Trial Overview The trial is testing if taking Dapagliflozin daily for four weeks before surgery is safe and tolerable for patients with aggressive prostate cancer. The drug's effects will be monitored using a BIOSENSE Meter to ensure patient safety during the pre-surgery period.

Participant Groups

Group I: Dapagliflozin Experimental Treatment 1 Intervention

* Dapagliflozin will be initiated once daily approximately 6 weeks prior to planned prostatectomy * Dapagliflozin will be given at 10 mg by mouth once daily for 4 weeks (days 1-28) prior to prostatectomy.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

The Foundation for Barnes-Jewish Hospital

Collaborator

Trials

43

Recruited

6,600+

Findings from Research

In a study of 167 patients with both diabetes mellitus and prostate cancer, the use of antidiabetic drugs like metformin and insulin did not significantly affect prostate cancer aggressiveness or progression, as measured by Gleason scores and other clinical parameters.

However, tissue analysis indicated that metformin and insulin users had decreased activation of the mTOR pathway and changes in androgen receptor levels, suggesting that these drugs may influence tumor biology differently compared to those not using antidiabetic medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidiabetic drugs influence molecular mechanisms in prostate cancer. Pircher, A., Zieher, M., Eigentler, A., et al.[2020]

In a study of 247 men with diabetes and prostate cancer, higher HbA1c levels were linked to more aggressive prostate tumors, as indicated by higher Gleason scores, suggesting that poor glycemic control may influence tumor biology.

Despite the association with tumor aggressiveness, higher HbA1c levels did not correlate with an increased risk of biochemical recurrence after treatment, indicating that glycemic control may not affect long-term outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycemic control and prostate cancer progression: results from the SEARCH database. Kim, HS., Presti, JC., Aronson, WJ., et al.[2022]

In the REDUCE trial, which included mandatory biopsies for all participants, diabetes was not linked to a lower risk of prostate cancer (PCa), showing an odds ratio of 1.01, indicating equal risk for diabetic and non-diabetic men.

The study suggested that obesity may modify the relationship between diabetes and high-grade PCa, with diabetic normal-weight men having a decreased risk, while obese men showed an increased risk, highlighting the complex interaction between these factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes and prostate cancer risk in the REDUCE trial. Wu, C., Moreira, DM., Gerber, L., et al.[2011]

In a study involving 106 men with recurrent prostate carcinoma, rosiglitazone did not significantly improve prostate specific antigen doubling time (PSADT) compared to placebo, indicating it may not be effective for this condition.

Both treatment groups had similar rates of disease progression, suggesting that rosiglitazone does not provide a therapeutic advantage over placebo in managing rising PSA levels after prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosiglitazone versus placebo for men with prostate carcinoma and a rising serum prostate-specific antigen level after radical prostatectomy and/or radiation therapy. Smith, MR., Manola, J., Kaufman, DS., et al.[2022]

In a study of 552 patients (276 with diabetes mellitus and 276 without), diabetes did not negatively affect short-term overall survival rates in prostate cancer patients, with 5-year survival rates of 88% for those with diabetes compared to 93% for those without.

Prostate cancer and its treatment did not significantly impact glycemic control in patients with diabetes, indicating that having both conditions does not worsen health outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CO-EXISTING PROSTATE CANCER AND DIABETES MELLITUS: IMPLICATIONS FOR PATIENT OUTCOMES AND CARE. Karlin, NJ., Amin, SB., Verona, PM., et al.[2022]

In a 12-week randomized controlled trial involving patients with type 2 diabetes, both empagliflozin and dapagliflozin significantly reduced body weight, fasting blood glucose, and HbA1c levels, indicating their efficacy as add-on therapies to traditional medications.

Empagliflozin was found to be more effective than dapagliflozin in reducing body mass index (BMI), fasting blood glucose, and HbA1c levels, while both medications had good safety profiles, with fewer urinary and genital infections reported in the empagliflozin group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Efficacy and Safety Profile of Sodium-Glucose Cotransporter-2 Inhibitors as Add-On Therapy in Patients With Type 2 Diabetes. Hussain, M., Elahi, A., Iqbal, J., et al.[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 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 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]

Sodium-glucose co-transporter-2 inhibitors (SGLT2-Is) are linked to a higher incidence of adverse events, particularly infections, metabolic disorders, renal issues, and reproductive system disorders, based on an analysis of 19,775 reports from international pharmacovigilance databases.

A significant concern is the potential for skin toxicity, including severe skin reactions, especially in women aged 18-65 using SGLT2-Is as their only diabetes treatment, highlighting the need for ongoing monitoring and vigilance by healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events with sodium-glucose co-transporter-2 inhibitors: A global analysis of international spontaneous reporting systems. Raschi, E., Parisotto, M., Forcesi, E., et al.[2018]

SGLT2 inhibitors effectively lower HbA1c levels by 0.5-1.5% in patients with type 2 diabetes without causing hypoglycemia, making them a safe option for improving glycemic control.

These medications have a unique mechanism of action that allows them to be used alongside other diabetes treatments, but they require careful monitoring for potential safety issues, especially in elderly or high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGLT2 inhibition in diabetes mellitus: rationale and clinical prospects. Ferrannini, E., Solini, A.[2022]

SGLT2 inhibitors effectively lower blood glucose levels in type 2 diabetes patients by increasing urinary glucose excretion, with reported reductions in fasting plasma glucose (FPG) by 14.4 to 45.8 mg/dL and HbA1c by 0.35 to 1.24%.

These medications are particularly beneficial for young, obese type 2 diabetics without renal impairment, but their effectiveness is reduced in patients with renal issues, making them more suitable as add-on therapy rather than first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Mechanisms and efficacy of SGLT2 inhibitors]. Shiba, T.[2018]

SGLT-2 inhibitors, like dapagliflozin, are a new class of oral diabetes medications that improve blood sugar control through an insulin-independent mechanism and also provide heart and kidney protection.

Recent research into SGLT-1 inhibition offers a promising new approach to managing high blood sugar, leading to the development of new drugs that target both SGLT-1 and SGLT-2, potentially enhancing treatment options for diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium-Glucose Cotransporter Inhibitors as Antidiabetic Drugs: Current Development and Future Perspectives. Maccari, R., Ottanà, R.[2023]

SGLT2 inhibitors, like dapagliflozin, help lower blood sugar levels by increasing glucose excretion in urine, working independently of insulin, which is a unique mechanism among diabetes medications.

Clinical trials and real-life studies show that dapagliflozin not only improves glycemic control by reducing glycosylated hemoglobin but also contributes to weight loss and lower blood pressure, offering additional metabolic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Impact of dapagliflozin on cardiovascular risk factors. Beyond glycemic control]. Pallarés, V., Escobar, C., Egocheaga, I., et al.[2021]

References

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

Antidiabetic drugs influence molecular mechanisms in prostate cancer. [2020]

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

Glycemic control and prostate cancer progression: results from the SEARCH database. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Diabetes and prostate cancer risk in the REDUCE trial. [2011]

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

Rosiglitazone versus placebo for men with prostate carcinoma and a rising serum prostate-specific antigen level after radical prostatectomy and/or radiation therapy. [2022]

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

CO-EXISTING PROSTATE CANCER AND DIABETES MELLITUS: IMPLICATIONS FOR PATIENT OUTCOMES AND CARE. [2022]

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

Comparison of Efficacy and Safety Profile of Sodium-Glucose Cotransporter-2 Inhibitors as Add-On Therapy in Patients With Type 2 Diabetes. [2021]

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

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

8. Belgium pubmed.ncbi.nlm.nih.gov

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

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

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

10. Netherlands pubmed.ncbi.nlm.nih.gov

Adverse events with sodium-glucose co-transporter-2 inhibitors: A global analysis of international spontaneous reporting systems. [2018]

11. England pubmed.ncbi.nlm.nih.gov

SGLT2 inhibition in diabetes mellitus: rationale and clinical prospects. [2022]

12. Japan pubmed.ncbi.nlm.nih.gov

[Mechanisms and efficacy of SGLT2 inhibitors]. [2018]

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

SGLT2 inhibitors: molecular design and potential differences in effect. [2022]

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

Sodium-Glucose Cotransporter Inhibitors as Antidiabetic Drugs: Current Development and Future Perspectives. [2023]

15. Spain pubmed.ncbi.nlm.nih.gov

[Impact of dapagliflozin on cardiovascular risk factors. Beyond glycemic control]. [2021]