Metformin for Prostate Cancer Patients with Glucose Intolerance or Overweight

(PragMet Trial)

Recruiting in Palo Alto (17 mi)

+3 other locations

Overseen by Thomas W. Flaig

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: University of Colorado, Denver

Must not be taking: Antidiabetics, Carbonic anhydrase inhibitors

Disqualifiers: Diabetes therapy, Liver disease, others

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

Metformin is used widely in the treatment of type 2 diabetes. It has off-label indications for use in the prevention of diabetes and in hyperinsulinar obesity. In medical practices, the implementation of metformin for these off-label indications is variable, often at the level of the provider. Multiple retrospective investigations have also shown a clinical benefit in men with prostate cancer who are incidentally treated with metformin. This pragmatic study will test the feasibility of enrolling patients who have glucose intolerance (as defined by HbA1c of 5.7-6.4%) and/or who have increased BMI (BMI greater than or equal to 25 kg/m2) to a randomized pragmatic study of metformin plus lifestyle modification information versus lifestyle modification information only. For purposes of the scope of this project and the study's feasibility, this will be implemented in a group of prostate cancer patients, who may have additional benefits from metformin.

Will I have to stop taking my current medications?

If you are currently taking medications for diabetes or any drugs that interact with metformin, you will need to stop those before joining the trial. This includes medications like insulin, glipizide, and others listed in the exclusion criteria.

What data supports the effectiveness of the drug Metformin for prostate cancer patients with glucose intolerance or overweight?

Research suggests that Metformin may help improve survival rates and reduce the risk of prostate cancer progression, especially in patients with diabetes. It has shown potential benefits in reducing the development of more aggressive forms of prostate cancer. ^{1 2 3 4 5}

Is metformin safe for humans?

Metformin is generally considered safe and well-tolerated in humans, as it is widely used to treat type 2 diabetes and has been studied for its potential benefits in prostate cancer treatment. ^{6 7 8 9 10}

How is the drug metformin unique for treating prostate cancer?

Metformin is unique for prostate cancer treatment because it is a well-tolerated, inexpensive drug that can be added to standard therapies, potentially reducing side effects of hormone therapy and providing additional anticancer benefits. It is traditionally used for type 2 diabetes, but its repurposing for prostate cancer is being explored for its potential to improve outcomes. ^{3 5 6 7 9}

Eligibility Criteria

Men over 18 with prostate cancer and either glucose intolerance (HbA1c of 5.7-6.4%) or a BMI≥25 kg/m2 can join this study if they have an MHC Account, consent to participate, and are under the care of a participating UCHealth provider. They must not be on certain drugs that interact badly with metformin, have severe kidney issues, liver diseases like cirrhosis or fibrosis, alcohol disorders, or allergies to metformin.

Inclusion Criteria

I am a man aged 18 or older.

You have high blood sugar or are overweight, and can take metformin.

Provision to sign and date the consent form in MHC or otherwise via Epic

Exclusion Criteria

I am not on medications that badly interact with metformin.

I have not taken any medication that increases the risk of lactic acidosis.

Contraindication for metformin use which include any of the following which are exclusionary (in Epic will use most recent lab values): Estimated glomerular filtration rate (eGFR) of < 50 ml/minute (calculated according to the formula utilized within Epic), Known Total Bilirubin ≥3 mg/dL, Diagnosis of fibrosis or cirrhosis of the liver (ICD10: K74), Diagnosis of alcohol related disorders (ICD10: F10), Metformin allergy in Epic (ICD10: T50.995A), Non-English-speaking patient until Spanish language consent form and relevant materials can be made available. Due to the novel aspect of this trial, we plan to get some experience in treating approximately the first 50 patients, make any changes needed in the study operations and then implement a Spanish consent, as feasible

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either metformin plus lifestyle modification or lifestyle modification alone

2 years

Quarterly visits (virtual or in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 years

Long-term follow-up

Participants are monitored for prostate cancer progression and overall survival

10 years

Treatment Details

Interventions

• Metformin (Biguanide)

Trial Overview This trial is checking if adding metformin to lifestyle changes helps control blood sugar better than just lifestyle advice in men with prostate cancer who also have high blood sugar levels or are overweight. Participants will randomly receive either both treatments or only lifestyle modification information.

Participant Groups

Group I: Metformin and Lifestyle Modification Arm Active Control 2 Interventions

For the metformin arm: metformin will be obtained as a standard of care medication from the patient's general pharmacy. This will be given for a clinical indication (e.g. prediabetes or overweight/obese). It will not be supplied by the study, but billed to Medicare, self pay or 3rd party payer. Lifestyle modification and prediabetes information will be provided via MHC or other electronic means on a quarterly basis.

Group II: Lifestyle Modification Only Arm Placebo Group 1 Intervention

Patients randomized to this arm will receive standard lifestyle modification recommendations. This will include the general recommendation to increase exercise level mildly, after discussing with the medical provider. There is a potential low-level risk in increasing one's exercise levels.

Metformin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

🇪🇺 Approved in European Union as Glucophage for:

• Type 2 diabetes

🇺🇸 Approved in United States as Glucophage for:

• Type 2 diabetes

🇨🇦 Approved in Canada as Glucophage for:

• Type 2 diabetes

🇯🇵 Approved in Japan as Glucophage for:

• Type 2 diabetes

🇨🇳 Approved in China as Glucophage for:

• Type 2 diabetes

🇨🇭 Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Colorado Research Center Aurora, CO

UCHealth-Metro Denver Denver, CO

UCHealth-Northern Colorado Fort Collins, CO

UCHealth-Southern Colorado Colorado Springs, CO

Who Is Running the Clinical Trial?

University of Colorado, Denver Lead Sponsor

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Metformin and prostate cancer: reduced development of castration-resistant disease and prostate cancer mortality. [2022] In vitro data and early clinical results suggest that metformin has desirable antineoplastic effects and has a theoretical benefit on castration-resistant prostate cancer (CRPC).

2. England pubmed.ncbi.nlm.nih.gov

Impact of metformin on clinical outcomes among men with prostate cancer: a systematic review and meta-analysis. [2018] Conflicting evidence exists regarding the beneficial effects of metformin in prostate cancer. To determine the association between metformin and clinical outcomes in prostate cancer using systematic review and meta-analysis.

3. Sweden pubmed.ncbi.nlm.nih.gov

Preexisting diabetes, metformin use and long-term survival in patients with prostate cancer. [2022] To assess prostate cancer-specific and overall survival in prostate cancer patients with or without preexisting type 2 diabetes mellitus (T2DM) with regards to metformin use.

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

CO-EXISTING PROSTATE CANCER AND DIABETES MELLITUS: IMPLICATIONS FOR PATIENT OUTCOMES AND CARE. [2022] To investigate how diabetes mellitus (DM) impacts short-term overall survival (OS) for patients with prostate cancer and to examine how prostate cancer impacts glycemic control in DM.

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

Protective Effects of Metformin Against Biochemical Failure Following Radical Prostatectomy or Radiation Therapy in Localized Prostate Cancer. [2022] To assess the impact of metformin on biochemical failure (BF) in localized prostate cancers (PC) treated with radical prostatectomy or radiation therapy.

6. Korea (South) pubmed.ncbi.nlm.nih.gov

A novel biguanide derivative, IM176, induces prostate cancer cell death by modulating the AMPK-mTOR and androgen receptor signaling pathways. [2023] Metformin and phenformin, biguanide derivatives that are widely used to treat type 2 diabetes mellitus, have recently been shown to exert potential anticancer effects in prostate cancer. This study compared the antiprostate cancer effects of the novel biguanide derivative IM176 with those of metformin and phenformin.

7. Switzerland pubmed.ncbi.nlm.nih.gov

Repurposing Metformin as Therapy for Prostate Cancer within the STAMPEDE Trial Platform. [2021] Metformin is a safe, well-tolerated, inexpensive treatment that can be given in addition to current standard-of-care therapies for prostate cancer. Its use might mitigate the deleterious side effects of castration and exert an additional anticancer effect. It will be incorporated in the STAMPEDE trial platform in summer 2016. This will test its true utility as a repurposed treatment for men with high-risk locally advanced or metastatic prostate cancer at first presentation.

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

Risk of New-Onset Prostate Cancer for Metformin Versus Sulfonylurea Use in Type 2 Diabetes Mellitus: A Propensity Score-Matched Study. [2022] The aim of this study was to compare the risks of new-onset prostate cancer between metformin and sulfonylurea users with type 2 diabetes mellitus (T2DM).

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

The Relationship Between Metformin and Serum Prostate-Specific Antigen Levels. [2018] Metformin is the first-line oral antihyperglycemic of choice for individuals with type 2 diabetes. Recent evidence supports a role for metformin in prostate cancer chemoprotection. However, whether metformin indeed influences prostate biology is unknown. We aimed to study the association between metformin and serum prostate-specific antigen (PSA) levels-the primary prostate cancer biomarker.

10. Poland pubmed.ncbi.nlm.nih.gov

Metformin is not associated with improved biochemical free survival or cause-specific survival in men with prostate cancer treated with permanent interstitial brachytherapy. [2022] Several recent studies have suggested improved clinical outcomes in diabetic men with prostate cancer who also use metformin. We explore whether metformin use is associated with improved outcomes specifically in men undergoing prostate brachytherapy.