Investigation of interaction between sodium-glucose cotransporter 2 inhibitors and FOLFOX with colorectal cancer and type 2 diabetes

doi:10.4251/wjgo.v18.i6.117912

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Randomized Controlled Trial

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastrointest Oncol. Jun 15, 2026; 18(6): 117912
Published online Jun 15, 2026. doi: 10.4251/wjgo.v18.i6.117912

Investigation of interaction between sodium-glucose cotransporter 2 inhibitors and FOLFOX with colorectal cancer and type 2 diabetes

Bin Liu, Ning Su, Qing-Shi Lin, Yan-Qin Huang, Shao-Feng Chen

Bin Liu, Department of Pharmacy, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, Hubei Province, China

Ning Su, Department of Nutritional, Shanghai Second Rehabilitation Hospital, Shanghai 200000, China

Qing-Shi Lin, Yan-Qin Huang, Shao-Feng Chen, Department of Pharmacy, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian Province, China

Co-first authors: Bin Liu and Ning Su.

Author contributions: Liu B and Su N have played important and indispensable roles in the experimental design as co-first authors; Liu B, Su N, Lin QS, and Huang YQ contributed to research design, data collection, data analysis, and paper writing; Chen SF was responsible for research design, funding application, data analysis, reviewing and editing, communication coordination, ethical review, copyright and licensing, and follow-up; all of the authors read and approved the final version of the manuscript to be published.

AI contribution statement: We used DeepL to assist in polishing the language of the manuscript. However, we did not use AI to write the content of the manuscript. The entire content (abstract, introduction, materials and methods, results, discussion, and conclusion) of this manuscript, except for some parts, was not generated by AI. The entire main content of this article was written by the author. The design of the study and the interpretation of the results were completed by the author. All the pictures were created by the author and no AI technology was used.

Institutional review board statement: The research was reviewed and approved by Hubei Cancer Hospital, No. LLHBCH2025YN-096.

Clinical trial registration statement: This study has not yet been registered with clinical trials.

Informed consent statement: All participants provided informed consent.

Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.

CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.

Data sharing statement: No other data available.

Corresponding author: Shao-Feng Chen, Associate Chief Pharmacist, Department of Pharmacy, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, No. 201 Hubin South Road, Xiamen 361004, Fujian Province, China. csfcby@163.com

Received: January 16, 2026
Revised: February 2, 2026
Accepted: March 6, 2026
Published online: June 15, 2026
Processing time: 143 Days and 18.8 Hours

Abstract

BACKGROUND

For stage III colorectal cancer (CRC) patients with type 2 diabetes mellitus (T2DM), the standard mFOLFOX6 adjuvant chemotherapy is often challenged by disease recurrence and chemotherapy-induced toxicities. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, beyond glycemic control, exhibit potential antitumor properties in preclinical studies, yet robust clinical evidence for their combination with FOLFOX is scarce. We hypothesized that adding the SGLT2 inhibitor dapagliflozin to mFOLFOX6 would improve glycemic control, enhance oncological outcomes, and not significantly increase chemotherapy-related toxicities in this comorbid patient population.

AIM

To investigate the efficacy and safety of dapagliflozin combined with mFOLFOX6 in stage III CRC patients with T2DM.

METHODS

This single-center, randomized controlled trial at a tertiary hospital enrolled 160 patients with stage III CRC and T2DM post-R0 resection. They were assigned to receive either dapagliflozin plus mFOLFOX6 (experimental group) or mFOLFOX6 with standard non-SGLT2 inhibitors glucose management (control group) for 12 cycles. Key outcomes included 3-year disease-free survival (DFS), tumor markers (carcinoembryonic antigen, carbohydrate antigen 19-9), glycemic control (glycated hemoglobin, fasting blood glucose), and adverse events. Data were analyzed using t-tests, χ² tests, and Kaplan-Meier with log-rank test.

RESULTS

The experimental group (n = 80) showed superior glycemic control (post-treatment glycated hemoglobin: 6.79% ± 0.79% vs 7.75% ± 0.59%, P < 0.001) and greater reductions in tumor markers (post-treatment carcinoembryonic antigen: 3.59 ± 1.24 ng/mL vs 4.52 ± 1.15 ng/mL, P < 0.001) compared to the control group (n = 80). The 3-year DFS was significantly higher (43.75% vs 22.5%, P = 0.004), with a prolonged median DFS (31.6 months vs 19.0 months, P < 0.001). The incidence of grade ≥ 3 chemotherapy-related adverse events was not significantly different between groups (56.25% vs 47.5%, P = 0.268). Specific SGLT2 inhibitor-associated events (e.g., acute kidney injury, diabetic ketoacidosis) occurred but were manageable.

CONCLUSION

Adding dapagliflozin to mFOLFOX6 improves glycemic control, tumor marker response, and survival in stage III CRC patients with T2DM, without significantly increasing chemotherapy-specific toxicities.

Keywords: Sodium-glucose cotransporter 2 inhibitors; Colorectal cancer; mFOLFOX6; Type 2 diabetes mellitus; Survival rate; Dapagliflozin

Core Tip: In this study, we evaluated the addition of the sodium-glucose cotransporter 2 inhibitor dapagliflozin to standard mFOLFOX6 chemotherapy in patients with stage III colorectal cancer and type 2 diabetes mellitus after curative resection. The combination significantly improved glycemic control, reduced carcinoembryonic antigen levels, and enhanced 3-year disease-free survival without increasing severe chemotherapy-related toxicity. These findings suggest that sodium-glucose cotransporter 2 inhibitor may offer dual metabolic and oncological benefits in this high-risk comorbid population, supporting its repurposing as an adjunct to adjuvant chemotherapy.