RecruitingEarly Phase 1NCT05515978

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

A Randomized, Pragmatic, Adaptive Trial of Metformin for Glucose Intolerance or Increased Body Mass Index in Prostate Cancer Patients

Sponsor

University of Colorado, Denver

Enrollment

100 participants

Start Date

Oct 10, 2022

Study Type

INTERVENTIONAL

Conditions

Prostate Cancer

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.

Eligibility

Sex: MALEMin Age: 18 Years

Inclusion Criteria9

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:
Provision to sign and date the consent form in MHC or otherwise via Epic.
Subjects must have an MHC Account to participate in the study
Be a male aged ≥18 years of age on day of signing the informed consent.
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
Have a prostate cancer diagnosis
Have a clinical relationship with a participating provider at a UCHealth facility.

Exclusion Criteria50

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):
Metformin
Insulin
Glipizide
Glyburide
Glimepiride
Pioglitazone
Rosiglitazone
Sitagliptin
Saxagliptin
Linagliptin
Alogliptin
Canagliflozin
Dapagliflozin
Empagliflozin
Ertugliflozin
Liraglutide
Dulaglutide
Semaglutide
Exenatide
Lixisenatide
Nateglinide
Repaglinide
Tirzepatide
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.
Taking any medication with a known class D or higher drug interaction with metformin, including:
Cimetidine
Dolutegravir
Patiromer
Ranolazine
Tafenoquine
The use of any carbonic anhydrase inhibitors since they are a risk factor for lactic acidosis, including:
Topiramate
Dichlorphenamide
Acetazolamide
Methazolamide
Dorzolamide
Brinzolamide
Dichlorphenamide
Sultiame
Zonisamide
Indisulam
Any treating investigator concern, related to tolerance, safety, adherence or for any other reason

Interventions

DRUGMetformin

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.

BEHAVIORALLifestyle 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