CompletedNCT01697566Updated Jun 11, 2025Results posted

An Endometrial Cancer Chemoprevention Study of Metformin

A Phase 3 interventional study of Metformin and Placebo in Gynecology, sponsored by M.D. Anderson Cancer Center. Completed at 1 site in United States. Open to female participants aged 50 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-06-11.

Sponsored by M.D. Anderson Cancer Center · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 29
Allocation: Randomized
Ages: 50 Years to 65 Years
Sex: Female

Study summary

The goal of this clinical research study is to learn about the effects of metformin and/or a program called "lifestyle intervention" on the endometrium (inner lining of the uterus) in post-menopausal women who are also obese (both are risk factors for endometrial cancer). Researchers also want to learn how insulin levels will be affected by metformin, diet and/or exercise.

Metformin is designed to treat both diabetes and insulin resistance. Insulin resistance is a condition in which the body makes insulin but does not use it properly. It is often referred to as "pre-diabetes". Many people with insulin resistance have high levels of both sugar and insulin in their blood at the same time, which have been reported in patients with endometrial cancer.

In this study, metformin will be compared to a placebo. A placebo is not a drug. It looks like the study drug but is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect.

Lifestyle intervention is made up of a series of in-person sessions where you meet with a coach to discuss strategies for losing weight and ways to increase physical activity. It also consists of materials designed to help you lose weight and will offer opportunities for supervised exercise.

Read the detailed description

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the roll of dice) to 1 of 4 study groups:

Metformin only.
Placebo and lifestyle intervention.
Metformin and lifestyle intervention.
Placebo only.

Neither you nor the study staff will know if you are receiving metformin or placebo. However, if needed for your safety, the study staff will be able to find out what you are receiving.

In the first month you will gradually increase the dose of metformin/placebo by mouth as listed below:

Week 1: One capsule each day
Week 2: One capsule 2 times each day
Week 3: One capsule 3 times each day
Week 4: Two capsules 2 times each day

After week 4, you will continue to take 2 capsules of metformin/placebo 2 times each day.

If you are receiving the lifestyle intervention, you will have 16 lifestyle intervention sessions over 4 months. At each of these sessions, you will discuss methods for managing your weight. You will receive print materials and worksheets, measuring utensils, and a food scale. You will be instructed how to use each of these materials and how often to use them during the study. You will also be provided with opportunities for supervised exercise (such as group exercise class and group walks).

If you are traveling during a scheduled session, it can be performed over the telephone. Each call should last about 30 minutes, during which you will discuss the same goals and information that you would discuss in the in-person sessions.

Study Visits:

Before you can begin receiving the study drug/placebo:

At the second screening visit , you will have a dual energy x-ray absorptiometry (DEXA) scan to measure your body composition. The scan requires you to lie still on a table for about 8-10 minutes while a low-energy x-ray takes an image that allows the study staff to get an image of your body fat density.
You will be given an accelerometer (a small, portable device that measures your physical activity) and be taught how to use it at the first Screening Visit. You will wear the accelerometer at all times while you are awake for 7 days. At the second Screening Visit, you will return the accelerometer at an intervention session. If you are not able to return it at the second visit then you will mail it back to the study staff in a pre-paid envelope. You will receive the accelerometer again at Month 4 and wear it for another 7 days.
You will receive a study diary in which you will record any and all exercise you perform each day while you are on study. It should take about 5 minutes to complete each time.
You will complete questionnaires about diet and exercise. These questionnaires should take about 30-40 minutes to complete.
You will also be taught to complete a questionnaire on the internet to record the food you eat in a 24 hour period. You will do this 3 times over a 2 week period. The first time, you will complete it at the clinic. The study staff will call and remind you to complete the questionnaire the other 2 times. Each time you complete this questionnaire, it should take about 40 minutes.

At Month 1, all participants will return for a study visit. The following tests and procedures will be performed:

Blood (about 2 teaspoons) will be drawn for routine tests. If this blood draw shows that your liver or kidney function is abnormal, you will need to return for an additional blood °draw at Month 2.
If you are having symptoms that you would describe as moderate or worse, you will have a non-pelvic physical exam including measurement of your vital signs and any unreported symptoms you may be having.

At each month, you will be asked about any symptom(s) that you may have to learn if it is related to the study. If you are called, this phone call should last about 5 minutes. If you are asked in a in-person visit, the visit can last up to an hour.

Length of Study:

You will receive the study drug/placebo and/or lifestyle intervention for up to 4 months. You will be taken off study if you have intolerable side effects or if you develop endometrial cancer or hyperplasia during the study. Your participation in the study will be over after the end-of-study visit.

Post-Treatment Visit:

At the end of the 4th month, you will have a post-treatment visit. You will repeat all procedures performed in the first and second visit:

Your height, weight, waist, and hip circumference will be measured.
You will have a DEXA scan.
You will complete the questionnaires about food, diet, and exercise.
You will be given a questionnaire about your satisfaction (based on the intervention) to complete and return at this visit. This questionnaire will take up to an hour to complete.
You will have an endometrial biopsy.
Blood (about 8 tablespoons) will be drawn for routine tests and for biomarker testing. You will have to fast (not eat or drink anything except water) for 12 hours before this blood draw.
You will complete the questionnaire on the internet to record the food you eat in a 24 hour period. You will do this 3 times over a 2 week period. The first time, you will complete it at the clinic. The study staff will call and remind you to complete the questionnaire the other 2 times. Each time you complete this questionnaire, it should take about 40 minutes.

Follow-Up:

About 1 year after the screening visits (+/- 1 month), the following tests and procedures will be performed:

Your height, weight, waist, and hip circumference will be measured.
You will have a DEXA scan.
Blood (about 8 tablespoons) will be drawn for routine tests and for biomarker testing. °You will have to fast (not eat or drink anything except water) for 12 hours before this blood draw.
You will wear the accelerometer for 7 days.
You will complete questionnaires about food, diet, and exercise.
You will complete the questionnaire on the internet to record the food you eat in a 24 hour period. You will do this 3 times over a 2 week period. The first time, you will complete it at the clinic. The study staff will call and remind you to complete the questionnaire the other 2 times. Each time you complete this questionnaire, it should take about 40 minutes.

This is an investigational study. Metformin is FDA approved and commercially available for the treatment of diabetes and insulin resistance.

Up to 100 patients will take part in this study. All will be enrolled at MD Anderson Cancer Center.

Conditions studied

Gynecology

Browse trials for

Endometrial Neoplasms 1,325

Keywords

Gynecology
Endometrial Cancer Chemoprevention
Obese
Body Mass Index (BMI) >/= 35 kg.m2
Post-menopausal
Hyperinsulinemia
Metformin
Placebo
Sugar pill
Lifestyle intervention
Diet
Exercise

In context

Endometrial Neoplasms

1,325 studies on the registry are indexed under Endometrial Neoplasms; 447 are open to participants now.

This study's enrollment of 29 is below the median of 70 across 941 interventional studies indexed under Endometrial Neoplasms.

Browse Endometrial Neoplasms studies →

Lead sponsor

M.D. Anderson Cancer Center is the lead sponsor of 2,999 studies on the registry; 581 are open to participants now.

Of its 599 completed or terminated interventional studies of FDA-regulated products, 402 (67%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 50 Years to 65 Years
Sexes eligible: Female
Accepts healthy volunteers: Yes

Inclusion criteria

For this study, only women will be enrolled.
Body Mass Index (BMI) > or = 30 kg/m2
Not frankly diabetic, as measured by a fasting blood glucose \</=126 mg/dL.
Demonstrate hyperinsulinemia with a QUICK I value \</= 0.357.
Age >/= 50 and \</= 65
Zubrod Performance Scale 0-1
Hemoglobin >/= 10 g/dl
TSH 0.27 - 4.20 µlU/mL
Menopause as defined as no menses for 1 year and/or FSH >/= 25.8 mIU/ml
Must be able to read, write, and speak English.
Must have a Primary Care Provider (PCP).

Exclusion criteria

Exclusion Criteria:

Prior hysterectomy or endometrial ablation
ALT >/r = 2.0x Upper Limit of Normal (ULN)
Serum creatinine > /= 1.4 mg/dl
Triglycerides (fasting) >/ = 400
Known inability to participate in the ongoing appointments for the four months of the study and scheduled follow-up tests.
Significant medical or psychiatric history which would make the participant a poor protocol candidate, in the opinion of the principal investigator, for any aspect of study participation including metformin, unsupervised exercise program or dietary behavior change.
Participant reported history of congestive heart failure
Prior treatment with Metformin
Currently being treated for diabetes or meeting criteria for new diagnosis of diabetes.
Known allergy to Metformin or other biguanide (Proguanil).
Use of Aromatase Inhibitors, GNRH-agonists i.e.Lupron, Zoladex within the last 6 months
Use of SERMS (selective estrogen receptor modulators) in the past 6 months, including Tamoxifen and Raloxifene
Hormone replacement therapy within the last 6 months
Women who have been treated with chemotherapy for prior malignant disease or currently have an untreated malignancy other than non-melanoma skin cancer
Patients who have had prior radiation to the pelvis

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 29 participants (actual)

Study arms

Experimental
Metformin
Participants gradually increase the dose of metformin by mouth as listed below: Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day After week 4, participant continues to take 2 capsules of metformin 2 times each day. Each capsule is 425 mg.
Drug: Metformin · Procedure: Endometrial Biopsy · Behavioral: Questionnaires
Experimental
Placebo + Lifestyle Intervention
Placebo taken by mouth twice daily for 4, 30 day cycles. Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.
Other: Placebo · Procedure: Endometrial Biopsy · Behavioral: Lifestyle Intervention · Behavioral: Questionnaires
Experimental
Metformin + Lifestyle Intervention
Participants gradually increase the dose of metformin by mouth as listed below: Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day After week 4, participant continues to take 2 capsules of metformin 2 times each day. Each capsule is 425 mg. Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.
Drug: Metformin · Procedure: Endometrial Biopsy · Behavioral: Lifestyle Intervention · Behavioral: Questionnaires
Placebo comparator
Placebo
Placebo taken by mouth twice daily for 4, 30 day cycles.
Other: Placebo · Procedure: Endometrial Biopsy · Behavioral: Questionnaires

Interventions

DrugMetformin
Participants gradually increase the dose of metformin by mouth as listed below: Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day After week 4, participant continues to take 2 capsules of metformin 2 times each day. Each capsule is 425 mg.
OtherPlacebo
Placebo taken by mouth twice daily for 4, 30 day cycles.
Also known as: sugar pill
ProcedureEndometrial Biopsy
Endometrial biopsies obtained at baseline and after 4 months.
BehavioralLifestyle Intervention
Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.
BehavioralQuestionnaires
Completion of questionnaires about diet and exercise at baseline, during treatment and at end of study. Questionnaires take about 30-40 minutes to complete.
Also known as: surveys

What researchers measure

Primary outcomes

To Evaluate the Participant Body Weight in Pounds (Lbs)
This study will use a 2 x 2 randomized design with all 100 post- menopausal subjects being randomized to metformin, placebo, placebo and intensive lifestyle intervention, or metformin and intensive lifestyle intervention. Treatments will last 4 months. Participants will be assessed at baseline and end of treatment with endometrial sampling to see if there are changes in the biomarkers.
Time frame: Visit 2 (1 week), 4 months, and 1 year
To Evaluate the Percentage of Ki-67 Positive Cells
The Q-PCR analyses will be performed in the Quantitative Genomics Core Facility at the University of Texas Medical School at Houston. Over the last 3 years we have used several techniques including differential display, microchip array screening, and real-time quantitative PCR to find such genes. The tools we have developed are directly applicable to the investigation of surrogate endpoint biomarkers (SEBs). Identification of appropriate biomarkers is essential for this study.
Time frame: Visit 2 (1 week), 4 months, and 1 year

Secondary outcomes

BMI
Time frame: Visit 2 (1 week), 4 months, and 1 year
Weight Loss
Time frame: Visit 2 (1 week), 4 months, and 1 year

Results

Posted Jun 11, 2025

Participant flow

Recruitment was from May 2013 until May 2016 and all recruitments were done in a medical clinic setting.

Participant flow — Overall Study
Milestone	Metformin + Lifestyle	Metformin + No Lifestyle	Placebo + Lifestyle	Placebo + No Lifestyle
Started	7	7	7	8
Completed	7	7	5	7
Not completed	0	0	2	1
Withdrew: Withdrawal by subject	0	0	1	1
Withdrew: Final biopsy not obtained	0	0	1	0

Outcome measures

PrimaryTo Evaluate the Participant Body Weight in Pounds (Lbs)

This study will use a 2 x 2 randomized design with all 100 post- menopausal subjects being randomized to metformin, placebo, placebo and intensive lifestyle intervention, or metformin and intensive lifestyle intervention. Treatments will last 4 months. Participants will be assessed at baseline and end of treatment with endometrial sampling to see if there are changes in the biomarkers.

Time frame:: Visit 2 (1 week), 4 months, and 1 year
Reported as:: Mean · lbs

To Evaluate the Participant Body Weight in Pounds (Lbs)
lbs	Metformin + Lifestyle	Metformin + No Lifestyle	Placebo + Lifestyle	Placebo + No Lifestyle
Weight Visit 2	108.57 ± 22.51	99.3 ± 15.36	101.64 ± 13.44	94.1 ± 12.89
Weight Month 4	101.19 ± 22.47	96.39 ± 15.36	97.98 ± 16.46	94.37 ± 13.46
Weight Year 1	102.08 ± 35.32	95.93 ± 12.63	93.25 ± 8.15	94.96 ± 13.68

Statistical analysis

Metformin + Lifestyle vs Placebo + Lifestyle · t-test, 2 sided · p = 0.006
Metformin + Lifestyle vs Placebo + Lifestyle · t-test, 2 sided · p = <0.001

PrimaryTo Evaluate the Percentage of Ki-67 Positive Cells

The Q-PCR analyses will be performed in the Quantitative Genomics Core Facility at the University of Texas Medical School at Houston. Over the last 3 years we have used several techniques including differential display, microchip array screening, and real-time quantitative PCR to find such genes. The tools we have developed are directly applicable to the investigation of surrogate endpoint biomarkers (SEBs). Identification of appropriate biomarkers is essential for this study.

Time frame:: Visit 2 (1 week), 4 months, and 1 year
Reported as:: Mean · percentage of cells

To Evaluate the Percentage of Ki-67 Positive Cells
percentage of cells	Metformin + Lifestyle	Metformin + No Lifestyle	Placebo + Lifestyle	Placebo + No Lifestyle
Visit 2	8.78 ± 8.29	7.95 ± 5.13	9.23 ± 3.96	4.73 ± 1.39
Month 4	6.73 ± 4.17	4.98 ± 3.94	4.17 ± 2.37	9.1 ± 5.96

SecondaryBMI

Time frame:: Visit 2 (1 week), 4 months, and 1 year
Reported as:: Mean · weight (kg) / height (m)2

BMI
weight (kg) / height (m)2	Metformin + Lifestyle	Metformin + No Lifestyle	Placebo + Lifestyle	Placebo + No Lifestyle
BMI Visit 2	45.25 ± 9.36	38.17 ± 5.18	39.49 ± 4.71	35.29 ± 4
BMI Month 4	39.83 ± 7.82	37.34 ± 4.78	37.83 ± 5.53	35.31 ± 4.16
BMI Year 1	41.13 ± 13.45	37.18 ± 4.41	36 ± 2.3	35.54 ± 4.23

Statistical analysis

Metformin + Lifestyle · t-test, 2 sided · p = 0.019

SecondaryWeight Loss

Time frame:: Visit 2 (1 week), 4 months, and 1 year
Reported as:: Mean · percentage of weight loss

Weight Loss
percentage of weight loss	Metformin + Lifestyle	Metformin + No Lifestyle	Placebo + Lifestyle	Placebo + No Lifestyle
Weight Loss (Month 4 - Visit 2)/Visit 2	-7.10 ± 5.22	-2.95 ± 2.34	-3.88 ± 5.11	0.25 ± 1.61
Weight Loss (Year 1 - Visit 2)/Visit 2	-5.49 ± 13.51	-3.09 ± 3.45	-3.37 ± 4.92	0.83 ± 0.95

Adverse events

Collected over An average of 36 months. Non-serious events are listed at a 1% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Metformin + Lifestyle	0/7 (0%)	0/7 (0%)	4/7 (57.1%)
Metformin + No Lifestyle	0/7 (0%)	0/7 (0%)	6/7 (85.7%)
Placebo + Lifestyle	0/7 (0%)	0/7 (0%)	4/7 (57.1%)
Placebo + No Lifestyle	0/8 (0%)	0/8 (0%)	4/8 (50%)

Most frequent other events

Showing 10 of 15

Most frequent other events
Event	Metformin + Lifestyle	Metformin + No Lifestyle	Placebo + Lifestyle	Placebo + No Lifestyle
DiarrheaGastrointestinal disorders	1/7	5/7	0/7	1/8
FlatulenceGastrointestinal disorders	2/7	4/7	2/7	4/8
HeadacheNervous system disorders	2/7	4/7	3/7	2/8
NauseaGastrointestinal disorders	1/7	3/7	0/7	1/8
Abdominal painGastrointestinal disorders	0/7	3/7	0/7	3/8
ConstipationGastrointestinal disorders	1/7	0/7	1/7	1/8
Blurred visionEye disorders	1/7	0/7	0/7	0/8
AnorexiaMetabolism and nutrition disorders	0/7	1/7	0/7	0/8
FatigueGeneral disorders	0/7	1/7	0/7	1/8
CoughRespiratory, thoracic and mediastinal disorders	0/7	0/7	0/7	1/8

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Metformin + Lifestyle	Metformin + No Lifestyle	Placebo + Lifestyle	Placebo + No Lifestyle	Total
<=18 years	0	0	0	0	0
Between 18 and 65 years	7	7	7	8	29
>=65 years	0	0	0	0	0

Age, Continuous
Age, Continuous(years)	Metformin + Lifestyle	Metformin + No Lifestyle	Placebo + Lifestyle	Placebo + No Lifestyle	Total
Median	56.3 (50 to 61)	56 (50 to 65)	57 (53 to 61)	59.8 (54 to 65)	57.4 (50 to 65)

Sex: Female, Male
Sex: Female, Male(Participants)	Metformin + Lifestyle	Metformin + No Lifestyle	Placebo + Lifestyle	Placebo + No Lifestyle	Total
Female	7	7	7	8	29
Male	0	0	0	0	0

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Metformin + Lifestyle	Metformin + No Lifestyle	Placebo + Lifestyle	Placebo + No Lifestyle	Total
Hispanic or Latino	0	1	2	2	5
Not Hispanic or Latino	4	4	2	4	14
Unknown or Not Reported	3	2	3	2	10

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Metformin + Lifestyle	Metformin + No Lifestyle	Placebo + Lifestyle	Placebo + No Lifestyle	Total
American Indian or Alaska Native	0	0	0	0	0
Asian	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	5	1	2	4	12
White	2	5	4	2	13
More than one race	0	0	0	0	0
Unknown or Not Reported	0	1	1	2	4

Region of Enrollment
Region of Enrollment(participants)	Metformin + Lifestyle	Metformin + No Lifestyle	Placebo + Lifestyle	Placebo + No Lifestyle	Total
United States	7	7	7	8	29

Study locations

1 site

University of Texas MD Anderson Cancer Center
Houston, Texas 77030, United States

References and documents

Study documents

Protocol and statistical analysis plan · May 13, 2013

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 11, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01697566
Lead sponsor: M.D. Anderson Cancer Center
Collaborators: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Oct 2, 2012
Start date: May 30, 2013
Primary completion: May 30, 2024
Completion: May 30, 2024
Results posted: Jun 11, 2025
Last update: Jun 11, 2025

Study contacts

Karen H. Lu, MD

principal investigator · M.D. Anderson Cancer Center

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in May 2025. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Endometrial Neoplasms→

Other studies from this sponsor

M.D. Anderson Cancer Center

Start the discussion