Metformin for the Treatment of Insulin Resistance in Women With Stage I-III Breast Cancer Completing Chemotherapy

January 21, 2026 updated by: City of Hope Medical Center

Metformin (Dimethylbiguanide) and Insulin Resistance in Women Completing Neoadjuvant and/or Adjuvant Cytotoxic Treatment of Stage I-III Breast Cancer

This phase III trial evaluates how often women develop insulin resistance and type-2 diabetes and compares metformin with usual care to usual care alone in treating insulin resistance in women with stage I-III breast cancer after chemotherapy. Insulin resistance occurs when cells stop responding to insulin and is a risk factor for developing diabetes and heart disease. Higher levels of insulin have been shown to be associated with aggressive breast cancer. Metformin hydrochloride decreases the amount of glucose (a type of sugar) released into the bloodstream from the liver and increases the body's use of the glucose. Metformin as well as standard of care diet and exercise education is known to lower blood sugar. However, chemotherapy may accelerate metabolic disorders, such as high blood sugar, and the impact of metformin in these breast cancer survivors is not known. Giving metformin with usual care may be more effective than usual care alone in preventing or reversing insulin resistance in women with stage I-III breast cancer after chemotherapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To determine if extended release metformin hydrochloride (metformin) can normalize glycosylated hemoglobin (HgbA1c) (< 5.7%) for women breast cancer survivors with HgbA1c between 5.7-6.4%.

EXPLORATORY OBJECTIVES:

I. To investigate whether metformin treatment of insulin resistance (versus standard of care alone) alters epigenetic changes (chromatin acetylation, chromatin opening, and methylation) and the level of inflammatory cytokines. (Pilot) II. To investigate whether normalization of HgbA1c alters epigenetic changes (chromatin acetylation, chromatin opening, and methylation) and the level of inflammatory cytokines. (Pilot)

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive standard of care healthy diet and exercise handouts and extended release metformin orally (PO) once daily (QD) for 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the study.

ARM II: Patients receive standard of care healthy diet and exercise handouts on study. Additionally, patients undergo blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30 days and in 12 months.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope Medical Center
        • Principal Investigator:
          • Victoria L. Seewaldt
        • Contact:
      • La Jolla, California, United States, 92093
        • Not yet recruiting
        • UC San Diego Moores Cancer Center
        • Contact:
        • Principal Investigator:
          • Shankar Subramaniam
      • Riverside, California, United States, 92521
        • Not yet recruiting
        • University of California-Riverside
        • Contact:
        • Principal Investigator:
          • Kendrick A. Davis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Documented informed consent of the participant and/or legally authorized representative

  • Agreement to allow lab draw of approximately 26 mL of blood (less than 3 tablespoons)

    • To check blood counts, organ function and disease at baseline and 12 months
    • Clinical labs at baseline, 3 months, 6 months,12 months, and 24 months
    • Research labs at baseline, 6 months,12 months, and 24 months
  • Age: ≥ 18 years
  • Female sex assigned at birth
  • Ability to read and understand English or Spanish for questionnaires
  • Diagnosis of estrogen receptor (ER)-negative /HER2-wild type or -amplified invasive mammary carcinoma stages I-III
  • Receive systemic treatment for breast cancer treatment
  • Completed treatment for stage 1-3 breast cancer within 90 days to 5 years and are disease free
  • Women who receive drugs for weight loss - e.g. semaglutide - prior to diagnosis are eligible for this protocol and can continue the drug during the intervention

Exclusion Criteria:

  • Currently taking metformin or any other oral antidiabetic medications. Weight loss medications are permitted - e.g. semaglutide
  • Taking tamoxifen or aromatase inhibitor
  • Contraindication to metformin prevention such as acute hypersensitivity or allergic reaction to metformin
  • Participants with acute or chronic renal insufficiency (a glomerular filtration rate [GFR] < 30 mL/min/1.73m^2) or those with acute renal insufficiency of any severity due to hepato-renal syndrome or in the peri-operative liver transplantation period
  • Previously diagnosed type 1 or type 2 diabetes
  • Patients pregnant or within 1 year of pregnancy and completion of lactation (pregnancy tests are standard of care [SOC] for initiation of chemotherapy)
  • Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • An employee who is under the direct/indirect supervision of the principal investigator (PI)/a co-investigator/the study manager and/or a direct study team member
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I (standard of care, metformin)
Patients receive standard of care healthy diet and exercise handouts and extended release metformin PO QD for 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the study.
Other: Questionnaire Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Extended Release Metformin Hydrochloride
Given PO
Other Names:
  • Glucophage XR
  • Glumetza
  • ER Metformin Hydrochloride
  • Extended-release Metformin Hydrochloride
  • Metformin Hydrochloride Extended Release
Other: Educational Intervention
Receive standard of care healthy diet and exercise handouts
Other Names:
  • Education for Intervention
  • Intervention by Education
  • Intervention through Education
  • Intervention, Educational
Active Comparator: Arm II (standard of care)
Patients receive standard of care healthy diet and exercise handouts on study. Additionally, patients undergo blood sample collection throughout the study.
Other: Questionnaire Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Other: Educational Intervention
Receive standard of care healthy diet and exercise handouts
Other Names:
  • Education for Intervention
  • Intervention by Education
  • Intervention through Education
  • Intervention, Educational

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hemoglobin A1c (Hgb A1c) normalization
Time Frame: Up to 12 months
Will be defined as Hgb A1c < 5.7%. Will be compared across groups (metformin + standard of care/usual medical care versus standard of care/usual medical care alone) using chi-square statistics. Data will be summarized using counts and percentages.
Up to 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HgbA1c normalization
Time Frame: At 3, 6, 12 and 24 months
Will compare HgbA1c normalization as well as pairwise t-tests across treatment groups to examine the magnitude of change in HgbA1c.
At 3, 6, 12 and 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Victoria L Seewaldt, City of Hope Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 16, 2024

Primary Completion (Estimated)

June 16, 2029

Study Completion (Estimated)

June 16, 2029

Study Registration Dates

First Submitted

January 2, 2025

First Submitted That Met QC Criteria

January 2, 2025

First Posted (Actual)

January 8, 2025

Study Record Updates

Last Update Posted (Actual)

January 22, 2026

Last Update Submitted That Met QC Criteria

January 21, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 24363 (Other Identifier: City of Hope Medical Center)
  • P30CA033572 (U.S. NIH Grant/Contract)
  • NCI-2024-10402 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U54CA285116 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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