Metformin increases pathological responses to rectal cancers with neoadjuvant chemoradiotherapy: a systematic review and meta-analysis

I-Li Lai; Jeng-Fu You; Wen-Sy Tsai; Yu-Jen Hsu; Yih-Jong Chern; Ming-Ying Wu

doi:10.1186/s12957-023-03087-6

Metformin increases pathological responses to rectal cancers with neoadjuvant chemoradiotherapy: a systematic review and meta-analysis

World J Surg Oncol. 2023 Jul 26;21(1):224. doi: 10.1186/s12957-023-03087-6.

Authors

I-Li Lai^{1

2

3}, Jeng-Fu You¹, Wen-Sy Tsai¹, Yu-Jen Hsu¹, Yih-Jong Chern¹, Ming-Ying Wu^{4

5}

Affiliations

¹ Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Guei-Shan District, Linkou Branch, No. 5, Fu-Hsing Street, Taoyuan City, Taiwan.
² Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, No. 259, Wenhua 1St Rd, Guei-Shan District, Taoyuan City, Taiwan.
³ Department of SurgeryTen-Chen Medical GroupZhongli Dist., Zhong-Li Metropolitan Hospital, Yanping Rd, No. 155, Taoyuan City, Taiwan.
⁴ Department of Dermatology, Chang Gung Memorial Hospital, Guei-Shan District, Linkou Branch, No. 5, Fu-Hsing Street, Taoyuan City, Taiwan. mini_robots@yahoo.com.tw.
⁵ Institute of Epidemiology and Preventive Medicine, Zhongzheng Dist., National Taiwan University, Xuzhou Rd, No. 17, Taipei City, Taiwan. mini_robots@yahoo.com.tw.

Abstract

Background: To summarize the chemo-radio effect of metformin in rectal cancers with neoadjuvant chemoradiotherapy on pathological response, tumor regression grade (TRG), and T/N downstaging.

Methods: PubMed, MEDLINE, Embase, and Cochrane Database of collected reviews were searched up to June 30, 2022. This study conducted systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) sheet. Odds ratios (ORs) and confidence intervals (CIs) which calculated by random-effects models were displayed in forest plots. Newcastle-Ottawa scale was used to assess the risk of bias of the observational cohort studies.

Results: This systematic review and meta-analysis comprised eight cohorts out of seven studies, with 2294 patients in total. We performed two-way comparison for metformin in diabetic patients vs (1) non-metformin drugs in diabetic patients and (2) nondiabetic patients. In diabetes patient studies, the metformin group had a significantly increased pathological response on TRG (OR: 3.28, CI: 2.01-5.35, I² = 0%, p < 0.001) and T downstaging (OR: 2.14, CI: 1.24-3.67, I² = 14%, p = 0.006) in comparison with a non-metformin group. When compared with nondiabetic patients, the pathological response on TRG (OR: 2.67, CI: 1.65-4.32, I² = 43%, p < 0.001) and T downstaging (OR: 1.96, CI: 1.04-3.71, I² = 66%, p = 0.04) were also higher in metformin group. The limitation was that no randomized controlled trials were available based on current literature review. Small sample sizes for diabetic metformin or non-metformin users in rectal cancer patients reduced the power of the study.

Conclusions: For patients with rectal cancer and treated with neoadjuvant chemoradiotherapy, metformin administration in diabetic patients increased the pathological response on tumor-regression grade and T downstaging. Further well-designed, high-quality randomized controlled trials are required to reveal the actual effect of metformin.

Keywords: Diabetes mellitus; Meta-analysis; Metformin; Neoadjuvant chemoradiotherapy; Pathological response; Rectal cancer.

Publication types

Meta-Analysis
Systematic Review
Review

MeSH terms

Chemoradiotherapy
Diabetes Mellitus* / drug therapy
Humans
Metformin* / therapeutic use
Neoadjuvant Therapy
Rectal Neoplasms* / pathology
Treatment Outcome

Substances

Metformin