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Pragmatic Trial of Metformin for Glucose Intolerance or Increased BMI in Prostate Cancer Patients
NCT05515978 · University of Colorado, Denver
In plain English
Click the button to translate this study into plain language — what it is, who qualifies, and what participation looks like.
Official title
A Randomized, Pragmatic, Adaptive Trial of Metformin for Glucose Intolerance or Increased Body Mass Index in Prostate Cancer Patients
About this study
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.
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
Study design
Enrollment target: 100 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2022-10-10
Estimated completion: 2036-11-06
Last updated: 2025-12-04
Interventions
Drug: MetforminBehavioral: Lifestyle Modification
Primary outcomes
- • Successful accrual of 100 patients to the pragmatic trial in the first four years (4 years)
Sponsor
University of Colorado, Denver · other
Contacts & investigators
ContactEmily Buchanan · contact · emily.buchanan@cuanschutz.edu · 303-724-5912
ContactMarjorie McIntyre · contact · marjorie.mcintyre@cuanschutz.edu · 303-724-5868
InvestigatorThomas Flaig, MD · principal_investigator, Colorado Research Center
All locations (4)
Colorado Research CenterRecruiting
Aurora, Colorado, United States
UCHealth-Southern ColoradoRecruiting
Colorado Springs, Colorado, United States
UCHealth-Metro DenverRecruiting
Denver, Colorado, United States
UCHealth-Northern ColoradoRecruiting
Fort Collins, Colorado, United States