Efficacy and Safety of Adjuvant Metformin for Operable Breast Cancer Patients

Study Overview
=================
Brief Summary
-----------------
The investigators hypothesize that adjuvant metformin use in breast cancer patients with overweight or pre-diabetes mellitus (DM) may improve their body condition including weight loss. In this study, the investigators aim to test the efficacy and safety of adjuvant metformin for operable breast cancer patients with overweight or pre-DM.

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: Metformin
* Drug: Metformin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Operable Breast cancer patients with BMI ≥ 23 or 100 ≤ FBS < 126 From 6 month to 2 years since breast cancer operation and at least 4 weeks since chemotherapy or radiotherapy No drug use except Tamoxifen Normal OTPT & Serum creatinine (<=ULN) ECOG performance status 0-2 or Karnofsky PS 60-100% Life expectancy > 12 Absolute neutrophil count ≥ 1.5 x 10^9/L Platelets ≥ 100 x 10^9/L Pregnancy(-) & without plan for pregnancy Sign a written informed consent form Exclusion Criteria: Type I or II DM or concurrent use of DM control agents Prior use of Metformin Hypoglycemia (FBS< 70 with clinical symptom) Concurrent investigational or commercial agents Other diet or drug intervention for weight loss Concurrent use of steroid Abnormal liver and/or renal function Symptomatic congestive heart failure / Cardiac arrhythmia / Angina pectoris Ongoing or active infection lactic acidosis Pregnancy or ongoing breast feeding Anorexia, bulimia, nausea due to other disease for longer than 1 month Allergies or allergic reactions attributed to oral medications Inability to swallow or digest oral medications Physical or psychiatric illness that would limit compliance with study protocol Participants in other clinical trial

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Control: Receive placebo pill once every evening on 1 2 weeks. Receive placebo pill in every morning and evening on 3 24 weeks (twice a day).<br>|
| Active Comparator: Metformin 500 mg/d<br>Metformin 500 mg/d | Drug: Metformin<br>* Metformin 500 mg/d: Receive oral metformin 500 mg dose once daily on 1 2 weeks. Receive placebo pill in every morning and oral metformin 500 mg in every evening on 3 24 weeks.<br>|
| Active Comparator: Metformin 1000 mg/d<br>Metformin 1000 mg/d | Drug: Metformin<br>* Metformin 1000 mg/d : Receive oral metformin 500 mg dose once daily on 1 2 weeks. (Dose-escalate) Receive oral metformin 500 mg in every morning and evening on 3 24 weeks (metformin 500 mg * twice a day = 1000 mg per day).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight loss |  | 6 months |