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      Metformin use is associated with a lower risk of uterine leiomyoma in female type 2 diabetes patients

      research-article
      Therapeutic Advances in Endocrinology and Metabolism
      SAGE Publications
      diabetes mellitus, metformin, Taiwan, uterine leiomyoma

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          Abstract

          Background:

          Whether metformin may reduce the risk of uterine leiomyoma in type 2 diabetes patients has not been investigated. This retrospective cohort study compared the risk of uterine leiomyoma in ever versus never users of metformin.

          Methods:

          Female patients with new-onset type 2 diabetes during 1999–2005 were enrolled from the reimbursement database of Taiwan’s National Health Insurance and followed up from 1 January 2006 until 31 December 2011. Analyses were conducted in a propensity score (PS) matched-pair cohort of 10,998 ever users and 10,998 never users of metformin. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using the PS.

          Results:

          A total of 321 never users and 162 ever users developed uterine leiomyoma during follow up, with respective incidence of 704.65 and 329.82 per 100,000 person-years. The overall hazard ratio was 0.467 (95% confidence interval: 0.387–0.564). The hazard ratios for the first (<23.3 months), second (23.3–53.1 months), and third (>53.1 months) tertiles of cumulative duration were 0.881 (0.685–1.132), 0.485 (0.367–0.642), and 0.198 (0.134–0.291), respectively; and were 0.751 (0.576–0.980), 0.477 (0.360–0.632), and 0.277 (0.198–0.386), respectively, for the first (<655,000 mg), second 655,000–1,725,500 mg), and third (>1,725,500) tertiles of cumulative dose. Sensitivity analyses after excluding users of sulfonylurea, users of estrogen, users of insulin, users of incretin-based therapies during follow up, patients with irregular drug refills, patients who discontinued the use of metformin, patients who received metformin prescription less than four times, or redefining uterine leiomyoma by using ‘diagnostic code’ plus ‘procedure codes’ consistently supported a lower risk of uterine leiomyoma in ever users of metformin.

          Conclusion:

          Metformin use is associated with a lower risk of uterine leiomyoma.

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          Most cited references30

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          Epidemiology of uterine fibroids: a systematic review

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            Problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes.

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              Metformin and Inflammation: Its Potential Beyond Glucose-lowering Effect.

              Metformin is an oral hypoglycemic agent which is most widely used as first-line therapy for type 2 diabetes. Metformin improves hyperglycemia by suppressing hepatic glucose production and increasing glucose uptake in muscle. Metformin also has been shown to reduce cardiovascular events in randomized controlled trials; however, the underlying mechanism remains to be established. Recent preclinical and clinical studies have suggested that metformin not only improves chronic inflammation through the improvement of metabolic parameters such as hyperglycemia, insulin resistance and atherogenic dyslipidemia, but also has a direct anti-inflammatory action. Studies have suggested that metformin suppresses inflammatory response by inhibition of nuclear factor κB (NFκB) via AMP-activated protein kinase (AMPK)-dependent and independent pathways. This review summarizes the basic and clinical evidence of the anti-inflammatory action of metformin and discusses its clinical implication.
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                Author and article information

                Journal
                Ther Adv Endocrinol Metab
                Ther Adv Endocrinol Metab
                TAE
                sptae
                Therapeutic Advances in Endocrinology and Metabolism
                SAGE Publications (Sage UK: London, England )
                2042-0188
                2042-0196
                18 December 2019
                2019
                : 10
                : 2042018819895159
                Affiliations
                [1-2042018819895159]Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei (100)
                [2-2042018819895159]Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei
                [3-2042018819895159]Division of Environmental Health and Occupational Medicine of the National Health Research Institutes, Zhunan
                Author notes
                Author information
                https://orcid.org/0000-0001-9545-7123
                Article
                10.1177_2042018819895159
                10.1177/2042018819895159
                6920594
                31897287
                aa28e08c-41da-42a2-a125-78d53f0e987d
                © The Author(s), 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 13 April 2019
                : 24 November 2019
                Funding
                Funded by: Ministry of Science and Technology, FundRef https://doi.org/10.13039/100007225;
                Award ID: MOST 107-2221-E-002-129-MY3
                Categories
                Original Research
                Custom metadata
                January-December 2019
                ts1

                diabetes mellitus,metformin,taiwan,uterine leiomyoma
                diabetes mellitus, metformin, taiwan, uterine leiomyoma

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