Pragmatic Trial of Metformin for Glucose Intolerance or Increased BMI in Prostate Cancer Patients

NCT ID: NCT05515978

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-10
• Study Completion Date: 2036-11-06

Brief Summary

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.

Detailed Description

In this study, subjects with prostate cancer will be randomized to metformin plus educational material for lifestyle modification versus educational material for lifestyle modification alone and followed for up to 10 years. Population-based, retrospective studies have reported improved outcomes, including prostate cancer specific mortality, with the incidental use of metformin in prostate cancer patients. One prominent study is this area from Margel, et al was published in 2013.2 Using the administrative database from several Ontario health districts, men aged 66 with incidental diabetes and prostate cancer antigen (PCA) were studied. The study included over 3000 men and found an adjusted hazard ratio of 0.76 (95% CI, 0.64 to 0.89) for PCA-specific mortality for each additional 6 months of metformin use. There was no relationship to survival with any other diabetic medication.

In addition to the use of metformin for the prevention of metabolic complications related to obesity and the prevention of diabetes, there are several studies reporting a potential benefit in those with prostate cancer. In a Veterans Administration-based study, more than 87,000 subjects were identified with PCA in the sample.3 The subjects were analyzed in 3 cohorts: 1) no diabetic medication (DM), 2) DM without metformin use and 3) DM with metformin use. Men with DM who were treated with metformin were found to have improved OS (HR 0.82, 95% CI 0.78 - 0.86, for mortality) compared to men with DM not on metformin. Reduced cancer specific mortality was also observed in the men with DM on metformin (HR 0.70, 95% CI 0.64 -0.77) in comparison to men with DM not taking metformin (HR 0.93, 95% CI 0.85 -1.00) - the reference group were those without DM. Despite considerable interest in these findings, there is little if any prospective data on the use of metformin in this setting.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lifestyle Modification Only Arm

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.

Group Type: PLACEBO_COMPARATOR

Lifestyle Modification

Intervention Type: BEHAVIORAL

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.

Here are some examples of the educational material from the American Diabetes Association website, and topics will be rotated on quarterly basis:

Healthy eating: https://www.diabetes.org/nutrition/healthy-food-choices-made-easy Prediabetes: https://www.diabetes.org/diabetes-risk/prediabetes Fitness: https://www.diabetes.org/fitness/get-and-stay-fit Weight loss: https://www.diabetes.org/fitness/weight-loss

Metformin and Lifestyle Modification Arm

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 Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Metformin is a medication used to treat type 2 diabetes, gestational diabetes, and prediabetes. In this study, patients on the Metformin arm will be started on 850 mg daily for 2 weeks, then escalated to a final dose of 850 mg twice daily, which is lower than the maximum recommended dose of 2550 mg total daily.

Lifestyle Modification

Intervention Type: BEHAVIORAL

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.

Here are some examples of the educational material from the American Diabetes Association website, and topics will be rotated on quarterly basis:

Healthy eating: https://www.diabetes.org/nutrition/healthy-food-choices-made-easy Prediabetes: https://www.diabetes.org/diabetes-risk/prediabetes Fitness: https://www.diabetes.org/fitness/get-and-stay-fit Weight loss: https://www.diabetes.org/fitness/weight-loss

Interventions

Metformin

Metformin is a medication used to treat type 2 diabetes, gestational diabetes, and prediabetes. In this study, patients on the Metformin arm will be started on 850 mg daily for 2 weeks, then escalated to a final dose of 850 mg twice daily, which is lower than the maximum recommended dose of 2550 mg total daily.

Intervention Type: DRUG

Lifestyle Modification

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.

Here are some examples of the educational material from the American Diabetes Association website, and topics will be rotated on quarterly basis:

Healthy eating: https://www.diabetes.org/nutrition/healthy-food-choices-made-easy Prediabetes: https://www.diabetes.org/diabetes-risk/prediabetes Fitness: https://www.diabetes.org/fitness/get-and-stay-fit Weight loss: https://www.diabetes.org/fitness/weight-loss

Intervention Type: BEHAVIORAL

Other Intervention Names

Glucophage; Riomet; Glumetza

Eligibility Criteria

Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria. The patients will be screening for eligibility and offered an electronic consent via the Epic medical record and the patient portal (My Health Connection - MHC) or otherwise through Epic:

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

2. Subjects must have an MHC Account to participate in the study

3. Be a male aged ≥18 years of age on day of signing the informed consent.

4. Impaired glucose tolerance and/or overweight, and appropriate to receive metformin, meeting at least one of the following in the last year (timing relative to the consent presentation not start of therapy):

• HbA1c of 5.7 - 6.4 %
• BMI≥25 kg/m^2

5. Have a prostate cancer diagnosis

6. Have a clinical relationship with a participating provider at a UCHealth facility.

Exclusion Criteria

1. On therapy for diabetes including any of the following alone or in combination medications (diet controlled or managed diabetes is allowed - e.g.

diagnosis of Diabetes, but without an active prescription for anti-glycemic medication):

1. Metformin

2. Insulin

3. Glipizide

4. Glyburide

5. Glimepiride

6. Pioglitazone

7. Rosiglitazone

8. Sitagliptin

9. Saxagliptin

10. Linagliptin

11. Alogliptin

12. Canagliflozin

13. Dapagliflozin

14. Empagliflozin

15. Ertugliflozin

16. Liraglutide

17. Dulaglutide

18. Semaglutide

19. Exenatide

20. Lixisenatide

21. Nateglinide

22. Repaglinide

23. Tirzepatide

2. Contraindication for metformin use which include any of the following which are exclusionary (in Epic will use most recent lab values):

1. Estimated glomerular filtration rate (eGFR) of < 50 ml/minute (calculated according to the formula utilized within Epic).

2. Known Total Bilirubin ≥3 mg/dL)

3. Diagnosis of fibrosis or cirrhosis of the liver (ICD10: K74)

4. Diagnosis of alcohol related disorders (ICD10: F10)

5. Metformin allergy in Epic (ICD10: T50.995A)

3. 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.

4. Taking any medication with a known class D or higher drug interaction with metformin, including:

1. Cimetidine

2. Dolutegravir

3. Patiromer

4. Ranolazine

5. Tafenoquine

5. The use of any carbonic anhydrase inhibitors since they are a risk factor for lactic acidosis, including:

1. Topiramate

2. Dichlorphenamide

3. Acetazolamide

4. Methazolamide

5. Dorzolamide

6. Brinzolamide

7. Dichlorphenamide

8. Sultiame

9. Zonisamide

10. Indisulam

6. Any treating investigator concern, related to tolerance, safety, adherence or for any other reason

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Flaig, MD

Role: PRINCIPAL_INVESTIGATOR

Colorado Research Center

Locations

Colorado Research Center

Aurora, Colorado, United States

Site Status: RECRUITING

UCHealth-Southern Colorado

Colorado Springs, Colorado, United States

Site Status: RECRUITING

UCHealth-Metro Denver

Denver, Colorado, United States

Site Status: RECRUITING

UCHealth-Northern Colorado

Fort Collins, Colorado, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Emily Buchanan

Role: CONTACT

emily.buchanan@cuanschutz.edu

303-724-5912

Marjorie McIntyre

Role: CONTACT

marjorie.mcintyre@cuanschutz.edu

303-724-5868

Facility Contacts

Marjorie McIntyre

Role: primary

marjorie.mcintyre@cuanschutz.edu

303-724-5868

Emily Buchanan

Role: backup

emily.buchanan@cuanschutz.edu

303-724-5912

Elizabeth Graf

Role: primary

elizabeth.graf@uchealth.org

Marjorie McIntyre

Role: primary

marjorie.mcintyre@cuanschutz.edu

303-724-5868

Sara Twombly

Role: primary

sara.twombly@uchealth.org

970-491-1553

Other Identifiers

NCI-2021-05911

Identifier Type: OTHER

Identifier Source: secondary_id

19-1536

Identifier Type: -

Identifier Source: org_study_id