Metformin and Risk of Malignant Brain Tumors in Patients with Type 2 Diabetes Mellitus

Abstract

The risk of malignant brain tumors associated with metformin use has rarely been investigated in humans. This retrospective cohort study investigated such an association. Patients with new-onset type 2 diabetes mellitus diagnosed from 1999 to 2005 in the nationwide database of Taiwan’s national health insurance were used to enroll study subjects. We first identified an unmatched cohort of 153,429 ever users and 16,222 never users of metformin. A cohort of 16,222 ever users and 16,222 never users matched on propensity score was then created from this unmatched cohort. All patients were followed up from 1 January 2006 until 31 December 2011. The incidence density was calculated and hazard ratios were derived from Cox regression incorporated with the inverse probability of treatment weighting using a propensity score. The results showed that 27 never users and 155 ever users developed malignant brain tumors in the unmatched cohort. The incidence rate was 37.11 per 100,000 person-years in never users and 21.39 per 100,000 person-years in ever users. The overall hazard ratio comparing ever users versus never users was 0.574 (95% confidence interval: 0.381–0.863). The respective hazard ratios comparing the first (<27.13 months), second (27.13–58.33 months), and third (>58.33 months) tertiles of cumulative duration of metformin therapy versus never users were 0.897 (0.567–1.421), 0.623 (0.395–0.984), and 0.316 (0.192–0.518). In the matched cohort, the overall hazard ratio was 0.317 (0.149–0.673) and the respective hazard ratios were 0.427 (0.129–1.412), 0.509 (0.196–1.322), and 0.087 (0.012–0.639) for the first, second, and third tertile of cumulative duration of metformin therapy. In conclusion, this study shows a risk reduction of malignant brain tumors associated with metformin use in a dose–response pattern. The risk reduction is more remarkable when metformin has been used for approximately 2–5 years.

Metformin Is Associated with a Lower Incidence of Benign Brain Tumors: A Retrospective Cohort Study in Patients with Type 2 Diabetes Mellitus

“…There are some clinical implications in the present study. First, together with the finding of a protective effect of metformin on malignant brain tumors seen in our previous study [11], metformin might also provide a protective effect on the development of BBT, in terms of cerebral meningioma and/or other types of BBT (Tables 2 and 3). These observations suggested that there might be some common pathophysiological pathways involved in the development of either malignant or benign brain tumors.…”

“…Major comorbidities included hypertension, dyslipidemia, obesity, chronic obstructive pulmonary disease, tobacco abuse, alcohol-related diagnoses and ocular pterygium (used as a surrogate of UV sunlight exposure). The ICD-9-CM codes for the above diagnoses have been described previously [11].…”

“…We recently found that patients with T2DM who had used metformin for more than two years had a significantly lower risk of malignant brain tumors [11]. However, epidemiological data evaluating the effect of metformin on the protection against BBT are still rare.…”

Demystifying the Relationship Between Metformin, AMPK, and Doxorubicin Cardiotoxicity

“…Several epidemiological studies, meta-analyses and animal studies have revealed that MET has anti-neoplastic and chemopreventive activities ( 20 , 81 ) despite mixed results observed in other studies ( 82 , 83 ). Indeed, diabetic patients taking MET have significantly reduced risk of cancer and lower cancer-related mortality ( 84 – 89 ). Several small-scale clinical trials have shown the ability of MET to induce favorable cellular and molecular changes in cancer patients ( 90 – 93 ).…”

Diabetes tracking panel: an on-line information system to registration and management

“…In addition, the diabetes is a disease with which clinical aspects are related to cardiovascular and cerebral accidents [9], [10], and today it is associated with mortality generated by COVID-19 [11], [12]. Therefore, it is important to prevent, diagnose and treat diabetes [13], [14].…”