Low-dose metformin, a first-line oral antidiabetic agent, reduced the prevalence and number of metachronous adenomas or polyps after polypectomy in patients with a high risk of adenoma recurrence, a study published in The Lancet Oncology has shown.1
Because no clinical trial data exist for the use of metformin for colorectal cancer chemoprevention, researchers sought to assess the safety and chemopreventive effects of metformin on sporadic colorectal cancer in patients who have had adenomas and are at high risk for recurrence.
For the multicenter, double-blind, phase 3 trial, researchers enrolled 151 nondiabetic adult patients who had previously had single or multiple colorectal adenomas or polyps resected by endoscopy. All patients received care from 1 of 5 hospitals in Japan.
Participants were randomly assigned 1:1 to receive metformin 250 mg orally daily or placebo. After 1 year of treatment, patients underwent colonoscopy to evaluate the number and prevalence of adenomas or polyps.
Results showed that among the 71 patients in the metformin group who underwent 1-year of follow-up, the total number of polyps and adenomas were 49 compared with 67 among the 62 patients in the placebo group.
Researchers found that the prevalence of total polyps was 38.0% (95% CI, 26.7 – 49.3) and 56.5% (95% CI, 44.1 – 68.8), respectively (RR, 0.67; 95% CI, 0.47 – 0.97; P = .034). The prevalence of adenomas was 30.6% (95% CI, 19.9 – 41.2) in the metformin group vs 51.6% (95% CI, 39.2 – 64.1) in the placebo arm (RR, 0.60; 95% CI, 0.39 – 0.92; P = .016).
Furthermore, the median number of polyps was 0 in the metformin group and 1 in the placebo group (P = .041), while the median number of adenomas was 0 in both groups (P = .037).
RELATED: Maintenance Capecitabine an Option for Metastatic Colorectal Cancer
In terms of safety, 11% of patients experienced adverse events, all of which were grade 1, suggesting that the administration of low-dose metformin for 1 year to patients without diabetes is safe.
The findings ultimately indicated that metformin has a potential role in the chemoprevention of colorectal cancer, but larger and longer trials are necessary to confirm these results.
- Higurashi T, Hosono K, Takahashi H, et al. Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial [published online ahead of print March 2, 2016]. Lancet Oncol. doi: 10.1016/S1470-2045(15)00565-3.