CHIN-HSIAO TSENG2021-10-122021-10-1220212218-273Xhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85115630106&doi=10.3390%2fbiom11101405&partnerID=40&md5=dd9e6838ba1dc1a2130e2951c7338009https://scholars.lib.ntu.edu.tw/handle/123456789/584379Background: The risk of benign brain tumors (BBT) associated with metformin use has not received much attention. Therefore, a retrospective cohort study was designed to investigate such an association in patients with type 2 diabetes mellitus (T2DM). Methods: We used the database of Taiwan’s National Health Insurance to enroll 152,176 ever users and 16,120 never users of metformin for the follow-up of incidence of BBT and a more specific outcome of cerebral meningioma. The patients were newly diagnosed with T2DM between 1999 and 2005; and they were followed up from 1 January 2006 until 31 December 2011. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. Results: During follow-up, 111 never users and 557 ever users were diagnosed with BBT. For BBT, the respective incidence rates for never users and ever users were 153.95 per 100,000 person-years and 77.61 per 100,000 person-years. While ever users were compared to never users, the hazard ratio was 0.502 (95% confidence interval: 0.409–0.615). A dose-response pattern was seen when ever users were categorized into tertiles of cumulative duration of metformin therapy (cutoffs: <27.10 months, 27.10–58.27 months and >58.27 months) with respective hazard ratios of 0.910 (0.728–1.138), 0.475 (0.375–0.602) and 0.243 (0.187–0.315). For cerebral meningioma, the overall hazard ratio was 0.506 (0.317–0.808); and the hazard ratios comparing the respective tertiles to never users were 0.895 (0.531–1.508), 0.585 (0.346–0.988) and 0.196 (0.104–0.369). Conclusions: A reduced risk of BBT and cerebral meningioma is observed in metformin users in patients with T2DM. ? 2021 by the author. Licensee MDPI, Basel, Switzerland.Benign brain tumors; Cerebral meningioma; Diabetes mellitus; Metformin; Taiwan[SDGs]SDG3acarbose; acetylsalicylic acid; angiotensin receptor antagonist; antidiabetic agent; calcium channel blocking agent; dipeptidyl carboxypeptidase inhibitor; fibric acid derivative; hydroxymethylglutaryl coenzyme A reductase inhibitor; insulin; meglitinide; metformin; pioglitazone; rosiglitazone; sulfonylurea; antidiabetic agent; metformin; adult; Article; brain tumor; cerebrovascular accident; chronic obstructive lung disease; cohort analysis; dyslipidemia; eye disease; female; follow up; human; hypertension; ICD-9-CM; ischemic heart disease; kidney disease; major clinical study; male; meningioma; non insulin dependent diabetes mellitus; obesity; peripheral occlusive artery disease; retrospective study; tobacco dependence; aged; brain tumor; complication; middle aged; neoplasm; non insulin dependent diabetes mellitus; pathology; risk factor; Taiwan; Aged; Brain Neoplasms; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Neoplasms; Retrospective Studies; Risk Factors; Taiwanjournal article10.3390/biom111014052-s2.0-85115630106