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.
Highlights
The incidence of malignant brain tumors (MBT) differs among different countries and glioblastoma is the most common adult primary MBT
The findings derived from the unmatched cohort and the matched cohort were very similar and a dose–response pattern in terms of the cumulative duration of metformin therapy was observed in the tertile analyses
Metformin use for more than 2 years in the second tertile in the unmatched cohort and more than approximately 5 years in the third tertile in the matched cohort was significantly associated with a reduced risk
Summary
The incidence of malignant brain tumors (MBT) differs among different countries and glioblastoma is the most common adult primary MBT. The age-adjusted incidence was reported to be 3.19 (during 2006–2010), 3.40 (during 2000–2008), 2.05 (during 1999–2003), 0.59 (during 2005), 3.69 (during 2005–2007), and 0.89 (during 2012–2013). In a recent statistical report derived from the Central Brain Tumor Registry of the United States (CBTRUS), the age-adjusted incidence rate of MBT during 2012–2016 was. 7.08 per 100,000 population [3], suggesting an increase in age-adjusted incidence in the USA compared to the rate of 3.19 per 100,000 population during 2006–2010, which was derived from the same dataset of the CBTRUS [4]. For the period from 1980–1984, Biomolecules 2021, 11, 1226.
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