Metformin enhances the pathological response in nondiabetic patients with rectal cancer undergoing neoadjuvant chemoradiotherapy: A randomized controlled trial
Abstract
This randomized, single-blind controlled pilot phase II trial evaluated whether adding metformin to neoadjuvant chemoradiotherapy (nCRT) increases pathological complete response (pCR) rates in nondiabetic patients with locally advanced rectal adenocarcinoma. Eighty-five nondiabetic patients treated between May 2024 and June 2025 were randomized to receive standard nCRT-radiotherapy 50.4 Gy in 28 daily fractions with concurrent oral capecitabine 825 mg/m2 twice daily (group A, n = 43)-or the same regimen plus oral metformin 1000 mg twice daily (group B, n = 42). Metformin was started 1 to 2 weeks before nCRT and continued until 30 days after completion. The primary endpoint was pCR, defined as the absence of residual tumor in the resected specimen; a composite endpoint combining pCR and clinical complete response (cCR) was also assessed. Group B achieved a significantly higher pCR rate than group A (28% vs 9%, P = .010). The combined pCR/cCR outcome was likewise superior in the metformin group (38% vs 14%, P = .011). In multivariable logistic regression adjusting for potential confounders, metformin remained an independent predictor of combined pCR/cCR (adjusted odds ratio 3.98, P = .031). Metformin added to nCRT appears to enhance tumor response and early clinical outcomes in nondiabetic patients with locally advanced rectal cancer and may represent a low-cost, low-toxicity radiosensitizer. Larger, long-term studies are warranted to confirm these findings and clarify their…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 43 participants or records.
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