Metformin use and survival from lung cancer: A population-based cohort study

Abstract

word count: 222 Manuscript word count: 1,472Number of tables and figures: 2 Abbreviations: BMI, body mass index; CIs, confidence intervals; CPRD, Clinical Practice Research Datalink; DDD, daily defined dose; GP, general practitioner; HR, hazard ratio; NCDR, National cancer Data Repository; ONS, Office of National Statistics; UK, United Kingdom; WHO, World Health Organisation. AbstractPreclinical evidence suggests that metformin, a widely prescribed anti-diabetic drug, may inhibit lung cancer progression. We investigated whether metformin use was associated with decreased risk of cancer-specific mortality in lung cancer patients. This study included newly diagnosed lung cancer patients (identified from English National Cancer Data Repository, 1998-2009) with type 2 diabetes (based on UK Clinical Practice Research Datalink prescriptions and diagnosis records). Lung cancer deaths occurring up to 2012 were identified using Office of National Statistics mortality data and the association between metformin use (before and after diagnosis) and risk of lung cancer-specific mortality was calculated using Cox regression models. In analysis of 533 patients, we found a weak non-significant reduction in lung cancer-specific mortality with metformin use after diagnosis (adjusted HR, 0.86; 95% CI, 0.68-1.09). No association was evident for metformin use before diagnosis and cancer-specific mortality in analysis of 1,350 patients (adjusted HR, 0.97; 95% CI, 0.86, 1.11). Associations were similar by duration of use. In addition, after adjustment for potential confounders, there was little evidence of an association between the use of other anti-diabetic medications (either before or after diagnosis) and lung cancer-specific mortality; including sulfonylureas, insulin or other anti-diabetic medications (such as thiazolidinediones). Overall, the results from this population-based study provide little evidence of a protective association between metformin use and cancer mortality in lung cancer patients.

The combination of metformin and 2‐deoxyglucose significantly inhibits cyst formation in miniature pigs with polycystic kidney disease

“…Notably, neither metformin nor 2DG has exhibited significant adverse side effects in the clinic (Lalau and Race, ; Dwarakanath et al ., ; Stein et al ., ). Metformin and 2DG have been studied in Phase I and II clinical studies in cancer patients (Cheong et al ., ; DePeralta et al ., ; Menamin et al ., ). Previous studies have shown that polycystic kidney cells are similar to tumour cells.…”

Effect of Metformin on Different Non-Diabetes Related Conditions, a Special Focus on Malignant Conditions: Review of Literature

“…These results were replicated in Menamin et al’s study, which assessed lung cancer patient registry between 1998 and 2009, and they found a weak favorable outcome when metformin was on board before or after diagnosis [63]. Interestingly, in the same study, there was a weak negative impact on other hypoglycemic agents like sulphonylureas and thiazolidinedione [63]. Further prospective studies are needed since the data in this perspective are contradicting.…”

“…However, another meta-analysis including 17 studies showed metformin had no survival benefit when used as an adjuvant with chemo-radiotherapy while it conferred a better survival outcome to lung cancer patients including those on chemotherapy only [62]. These results were replicated in Menamin et al’s study, which assessed lung cancer patient registry between 1998 and 2009, and they found a weak favorable outcome when metformin was on board before or after diagnosis [63]. Interestingly, in the same study, there was a weak negative impact on other hypoglycemic agents like sulphonylureas and thiazolidinedione [63].…”

Metformin use and survival after non‐small cell lung cancer: A cohort study in the US Military health system

“…There have been a few studies examining metformin use and survival among lung cancer patients 25–31 . However, the results have been inconsistent.…”

“…However, in another study of lung cancer patients (NSCLC and small cell lung cancer were not differentiated), pre-diagnostic use of metformin increased risk of death after adjustment for age and tumor stage 26 . Among studies that evaluated post-diagnostic metformin use 25–27, 29, 31 , a recent retrospective cohort study reported a non-significant HR of 0.86 (95% CI, 0.68 to 1.09) for lung cancer-specific mortality 31 , after adjustment for multiple variables, although cancer stage was not adjusted and NSCLC and small cell lung cancer were not differentiated. A small clinical trial reported improved overall survival with metformin use compared to those on other anti-diabetic drugs among advanced stage NSCLC patients 27 , while another small study found similar overall survival between patients with and without metformin use among locally advanced NSCLC patients 29 .…”