Metformin efficacy and safety for colorectal polyps: a double-blind randomized
controlled trial.
Author(s): Higurashi T, Takahashi H, Endo H, Hosono K, Yamada E, Ohkubo H, Sakai E, Uchiyama
T, Hata Y, Fujisawa N, Uchiyama S, Ezuka A, Nagase H, Kessoku T, Matsuhashi N,
Yamanaka S, Inayama Y, Morita S, Nakajima A.
Affiliation(s): Division of Gastroenterology, Yokohama City University School of Medicine,
Yokohama, Japan.
Publication date & source: 2012, BMC Cancer. , 12:118
BACKGROUND: Colorectal cancer is one of the major neoplasms and a leading cause
of cancer death worldwide, and new preventive strategies are needed to lower the
burden of this disease. Metformin, a biguanide, which is widely used for treating
diabetes mellitus, has recently been suggestive to have a suppressive effect on
tumorigenesis and cancer cell growth. In a previous study conducted in
non-diabetic subjects, we showed that oral short-term low-dose metformin
suppressed the development of colorectal aberrant crypt foci (ACF). ACF have been
considered as a useful surrogate biomarker of CRC, although the biological
significance of these lesions remains controversial. We devised a prospective
randomized controlled trial to evaluate the chemopreventive effect of metformin
against metachronous colorectal polyps and the safety of this drug in
non-diabetic post-polypectomy patients.
METHODS/DESIGN: This study is a multi-center, double-blind, placebo-controlled,
randomized controlled trial to be conducted in non-diabetic patients with a
recent history of undergoing colorectal polypectomy. All adult patients visiting
the Yokohama City University hospital or affiliated hospitals for polypectomy
shall be recruited for the study. Eligible patients will then be allocated
randomly into either one of two groups: the metformin group and the placebo
group. Patients in the metformin group shall receive oral metformin at 250 mg per
day, and those in the placebo group shall receive an oral placebo tablet. At the
end of 1 year of administration of metformin/placebo, colonoscopy will be
performed to evaluate the polyp formation.
DISCUSSION: This is the first study proposed to explore the effect of metformin
against colorectal polyp formation. Metformin activates AMPK, which inhibits the
mammalian target of rapamycin (mTOR) pathway. The mTOR pathway plays an important
role in the cellular protein translational machinery and cell proliferation.
Patients with type 2 diabetes taking under treatment with metformin have been
reported to be at a lower risk of cancer development than those not taking under
treatment with metformin. We showed in a previous study that metformin suppressed
the formation of human colorectal ACF. We therefore decided to conduct a study to
determine whether metformin might suppress the formation of human colorectal
polyps.
TRIAL REGISTRATION: This trial has been registered in the University hospital
Medical Information Network (UMIN) Clinical Trials Registry as UMIN000006254.
|