Efficacy of metformin therapy in patients with cancer: a meta-analysis of 22 randomised controlled trials

Abstract

Background To investigate whether metformin monotherapy or adjunctive therapy improves the prognosis in patients with any type of cancer compared to non-metformin users (age ≥18). Methods Databases (Medline, Embase, and the Cochrane Central Register of Controlled Trials) and clinical trial registries (ClinicalTrials.gov; the World Health Organization International Clinical Trials Registry Platform) were screened for randomized, controlled trials (RCT) reporting at least progression-free survival (PFS) and/or overall survival (OS). Main outcome measures included hazard ratios (HR), and combined HRs and 95% confidence intervals (CI) were calculated using random-effects models. Results Of the 8419 records screened, 22 RCTs comprising 5943 participants were included. Pooled HRs were not statistically significant in both PFS (HR 0.97, 95% CI 0.82–1.15, I2 = 50%) and OS (HR 0.98, 95% CI 0.86–1.13, I2 = 33%) for patients with cancer between the metformin and control groups. Subgroup analyses demonstrated that metformin treatment was associated with a marginally significant improvement in PFS in reproductive system cancers (HR 0.86, 95% CI 0.74–1.00) and a significantly worse PFS in digestive system cancers (HR 1.45, 95% CI 1.03–2.04). The PFS or OS was observed consistently across maintenance dose, diabetes exclusion, median follow-up, risk of bias, and combined antitumoral therapies. Conclusion Metformin treatment was not associated with cancer-related mortality in adults compared with placebo or no treatment. However, metformin implied beneficial effects in the PFS of the patients with reproductive system cancers but was related to a worse PFS in digestive system cancers. Systematic review registration PROSPERO registration number CRD42022324672.

The Geroprotective Drug Candidate CMS121 Alleviates Diabetes, Liver Inflammation, and Renal Damage in db/db Leptin Receptor Deficient Mice

“…Despite glucose-lowering drugs reducing blood sugar, they provide limited cardiovascular benefits, and often cause weight gain, especially with insulin and sulfonylurea drugs [ 16 , 17 ]. While metformin is a well-known glucose-lowering drug with benefits, it is not recommended for all patients, such as those with certain cancers, and has shown mixed results in terms of progression-free survival, with better outcomes in patients with reproductive cancers and worse outcomes in those with digestive system cancers [ 18 ].…”

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“…Brazilian Journal of Health Review, Curitiba, v. 7, n. 1, p. 2600-2611, jan./fev., 2024 terapia com metformina é potencialmente benéfica para cânceres do sistema reprodutivo, incluindo mama, ovário, endométrio e próstata (WEN, et al, 2022).…”

Drug repositioning in thyroid cancer treatment: the intriguing case of anti-diabetic drugs

“…Results from clinical studies regarding the anti-cancer effects of metformin are rather controversial. Indeed, while some retrospective-case control studies, have shown that metformin is able to reduce overall cancer incidence and mortality by 10%–40% ( IDF, 2021 ), RCTs failed to show a significant reduction in cancer incidence and mortality ( Stevens et al, 2012 ; Wen et al, 2022 ). This discrepancy could be due, at least in part, to the short follow-up time and/or to the biological heterogeneity of cancer.…”