<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">ometendo</journal-id><journal-title-group><journal-title xml:lang="ru">Ожирение и метаболизм</journal-title><trans-title-group xml:lang="en"><trans-title>Obesity and metabolism</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2071-8713</issn><issn pub-type="epub">2306-5524</issn><publisher><publisher-name>Endocrinology Research Centre</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.14341/omet2012211-16</article-id><article-id custom-type="elpub" pub-id-type="custom">ometendo-6540</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>Статьи</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>Неоднозначность данных об эффективности метформина как средства, снижающего массу тела и предотвращающего опухолевый рост: причины и следствия</article-title><trans-title-group xml:lang="en"><trans-title>Variable evidence on metformin efficiency as weight-reducing and antiblastomogenic agent: causes and consequences</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Berstein</surname><given-names>L M</given-names></name></name-alternatives><email xlink:type="simple">levmb@endocrin.spb.ru</email></contrib></contrib-group><pub-date pub-type="collection"><year>2012</year></pub-date><pub-date pub-type="epub"><day>15</day><month>06</month><year>2012</year></pub-date><volume>9</volume><issue>2</issue><issue-title>№2 (2012)</issue-title><fpage>11</fpage><lpage>16</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Berstein L.M., 2012</copyright-statement><copyright-year>2012</copyright-year><copyright-holder xml:lang="ru">Berstein L.M.</copyright-holder><copyright-holder xml:lang="en">Berstein L.M.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.omet-endojournals.ru/jour/article/view/6540">https://www.omet-endojournals.ru/jour/article/view/6540</self-uri><abstract><p>Растущий интерес к метформину в областях, лежащих за пределами диабетологии, служит стимулом для дополнительной оценки его эффективности как средства, влияющего на заболеваемость злокачественными новообразованиями и распространенность ожирения. Постепенно обнаруживаемые различия в выраженности этих эффектов препарата можно объяснить недостаточным количеством рандомизированных исследований, расхождениями в подходе к точке отсчета (группе сравнения), гендерными, возрастными, фармакогенетическими и иными факторами, изучение которых в совокупности обещает повысить вероятность более благоприятных клинических последствий применения метформина и, возможно, других бигуанидов.</p></abstract><trans-abstract xml:lang="en"><p>The growing interest to metformin in areas beyond the limits of diabetology serves as a stimulus for further evaluation of its effectiveness as a potential modulator of cancer morbidity and obesity epidemic. Gradually detectable differences in the intensity of these effects of the drug can be explained by an insufficient number of randomized trials, differences in the control groups (reference points), gender, age, pharmacogenetic and other factors, the study of which collectively promised to increase the likelihood of more favorable clinical effects of metformin and other antidiabetic biguanides in discussed areas.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>метформин</kwd><kwd>ожирение</kwd><kwd>онкологическая заболеваемость</kwd><kwd>модифицирующие факторы</kwd></kwd-group><kwd-group xml:lang="en"><kwd>metformin</kwd><kwd>obesity</kwd><kwd>cancer morbidity</kwd><kwd>modifying factors</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Александров АА. Прогноз сердечно-сосудистых осложнений при современной сахароснижающей терапии: Флорентийская модель. Болезни сердца и сосудов 2010;2:11-16.</mixed-citation><mixed-citation xml:lang="en">Александров АА. Прогноз сердечно-сосудистых осложнений при современной сахароснижающей терапии: Флорентийская модель. Болезни сердца и сосудов 2010;2:11-16.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Анисимов ВН. Антидиабетический бигуанид метформин как геропротектор и антиканцероген. Ожирение и метаболизм. 2011;3(28):18-24.</mixed-citation><mixed-citation xml:lang="en">Анисимов ВН. Антидиабетический бигуанид метформин как геропротектор и антиканцероген. Ожирение и метаболизм. 2011;3(28):18-24.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Берштейн ЛМ. Рак гормонозависимых тканей в системе основных неинфекционных заболеваний человека. Спб: Эскулап 2009:180 с.</mixed-citation><mixed-citation xml:lang="en">Берштейн ЛМ. Рак гормонозависимых тканей в системе основных неинфекционных заболеваний человека. Спб: Эскулап 2009:180 с.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Берштейн ЛМ. Бигуаниды: экспансия в практическую онкологию (прошлое и настоящее). Спб.: Эскулап 2010:144 с.</mixed-citation><mixed-citation xml:lang="en">Берштейн ЛМ. Бигуаниды: экспансия в практическую онкологию (прошлое и настоящее). Спб.: Эскулап 2010:144 с.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Берштейн ЛМ. Антидиабетический бигуанид метформин и онкологическая заболеваемость. Сахарный диабет 2010;3:45-48.</mixed-citation><mixed-citation xml:lang="en">Берштейн ЛМ. Антидиабетический бигуанид метформин и онкологическая заболеваемость. Сахарный диабет 2010;3:45-48.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Берштейн ЛМ, Коваленко ИГ. «Метаболически здоровые» лица с ожирением и метаболические признаки ожирения у лиц с нормальной массой тела: что за этим стоит? Пробл. эндокринол. 2010;3:47-51.</mixed-citation><mixed-citation xml:lang="en">Берштейн ЛМ, Коваленко ИГ. «Метаболически здоровые» лица с ожирением и метаболические признаки ожирения у лиц с нормальной массой тела: что за этим стоит? Пробл. эндокринол. 2010;3:47-51.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Берштейн ЛМ, Максимов СЯ, Данилова МА. и др. Сравнение эффектов ингибиторов ароматазы и метформина при их неоадъювантном применении у больных раком эндометрия. Вопр.онкол. 2011;57(6):737-741.</mixed-citation><mixed-citation xml:lang="en">Берштейн ЛМ, Максимов СЯ, Данилова МА. и др. Сравнение эффектов ингибиторов ароматазы и метформина при их неоадъювантном применении у больных раком эндометрия. Вопр.онкол. 2011;57(6):737-741.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Дедов ИИ, Бутрова СА, Берковская МА. Потенциальные возможности метформина в профилактике и лечении онкологических заболеваний у больных сахарным диабетом 2 типа. Ожирение и метаболизм 2011;1(26):40-50.</mixed-citation><mixed-citation xml:lang="en">Дедов ИИ, Бутрова СА, Берковская МА. Потенциальные возможности метформина в профилактике и лечении онкологических заболеваний у больных сахарным диабетом 2 типа. Ожирение и метаболизм 2011;1(26):40-50.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Дедов ИИ, Бутрова СА, Мищенко БП, Дзгоева ФК. Применение метформина (сиофора) у больных с абдоминальным типом ожирения. Проблемы эндокринол. 2000;46 (5): 25-29.</mixed-citation><mixed-citation xml:lang="en">Дедов ИИ, Бутрова СА, Мищенко БП, Дзгоева ФК. Применение метформина (сиофора) у больных с абдоминальным типом ожирения. Проблемы эндокринол. 2000;46 (5): 25-29.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Дедов ИИ, Мельниченко ГА, Романцова ТИ. Патогенетические аспекты ожирения. Ожирение и метаболизм 2004;1:3-9.</mixed-citation><mixed-citation xml:lang="en">Дедов ИИ, Мельниченко ГА, Романцова ТИ. Патогенетические аспекты ожирения. Ожирение и метаболизм 2004;1:3-9.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Дедов ИИ, Шестакова МВ. Сахарный диабет: острые и хронические осложнения. М.: МИА 2011:480 с.</mixed-citation><mixed-citation xml:lang="en">Дедов ИИ, Шестакова МВ. Сахарный диабет: острые и хронические осложнения. М.: МИА 2011:480 с.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Дильман ВМ. Четыре модели медицины. Л.: Медицина, 1987; 288 с.</mixed-citation><mixed-citation xml:lang="en">Дильман ВМ. Четыре модели медицины. Л.: Медицина, 1987; 288 с.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Дильман ВМ, Берштейн ЛМ, Цырлина ЕВ. и др. О коррекции эндокринно-обменных нарушений у онкологических больных. Эффект бигуанидов (фенформина и адебита), мисклерона и дифенина. Вопр.онкол. 1975;21(11):33-39.</mixed-citation><mixed-citation xml:lang="en">Дильман ВМ, Берштейн ЛМ, Цырлина ЕВ. и др. О коррекции эндокринно-обменных нарушений у онкологических больных. Эффект бигуанидов (фенформина и адебита), мисклерона и дифенина. Вопр.онкол. 1975;21(11):33-39.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Ивашкин ВТ, Маевская МВ. Липотоксичность и метаболические нарушения при ожирении. Росс. журн. гастроэнтерол., гепатол., колопроктол. 2010;20(1):4-13.</mixed-citation><mixed-citation xml:lang="en">Ивашкин ВТ, Маевская МВ. Липотоксичность и метаболические нарушения при ожирении. Росс. журн. гастроэнтерол., гепатол., колопроктол. 2010;20(1):4-13.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Попова ПВ, Рязанцева ЕМ, Зазерская ИЕ. и др. Роль снижения массы тела и приема метформина в восстановлении менструальной функции у женщин с синдромом поликистозных яичников и избыточной массой тела. Проблемы эндокринол 2011;57(2):14-18.</mixed-citation><mixed-citation xml:lang="en">Попова ПВ, Рязанцева ЕМ, Зазерская ИЕ. и др. Роль снижения массы тела и приема метформина в восстановлении менструальной функции у женщин с синдромом поликистозных яичников и избыточной массой тела. Проблемы эндокринол 2011;57(2):14-18.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Солун МН, Куницина МА. Сахарный диабет и злокачественные опухоли. Вопр. онкол. 1987;33(11):7-12.</mixed-citation><mixed-citation xml:lang="en">Солун МН, Куницина МА. Сахарный диабет и злокачественные опухоли. Вопр. онкол. 1987;33(11):7-12.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Anedda A, Rial E, González-Barroso MM. Metformin induces oxidative stress in white adipocytes and raises uncoupling protein 2 levels. J Endocrinol 2008;199(1):33-40.</mixed-citation><mixed-citation xml:lang="en">Anedda A, Rial E, González-Barroso MM. Metformin induces oxidative stress in white adipocytes and raises uncoupling protein 2 levels. J Endocrinol 2008;199(1):33-40.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Azoulay L, Dell&amp;amp;apos;Aniello S, Gagnon B et al. Metformin and the incidence of prostate cancer in patients with type 2 diabetes. Cancer Epidemiol Biomarkers Prev 2011;20(2):337-344.</mixed-citation><mixed-citation xml:lang="en">Azoulay L, Dell&amp;amp;apos;Aniello S, Gagnon B et al. Metformin and the incidence of prostate cancer in patients with type 2 diabetes. Cancer Epidemiol Biomarkers Prev 2011;20(2):337-344.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Bayraktar S, Hernadez-Aya LF, Lei X et al. Effect of metformin on survival outcomes in diabetic patients with triple receptor-negative breast cancer. Cancer. 2011 Jul 28. [Epub ahead of print]</mixed-citation><mixed-citation xml:lang="en">Bayraktar S, Hernadez-Aya LF, Lei X et al. Effect of metformin on survival outcomes in diabetic patients with triple receptor-negative breast cancer. Cancer. 2011 Jul 28. [Epub ahead of print]</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Becker S, Dossus L, Kaaks R. Obesity related hyperinsulinaemia and hyperglycaemia and cancer development. Arch Physiol Biochem 2009;115(2):86-96.</mixed-citation><mixed-citation xml:lang="en">Becker S, Dossus L, Kaaks R. Obesity related hyperinsulinaemia and hyperglycaemia and cancer development. Arch Physiol Biochem 2009;115(2):86-96.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Bo S, Ciccone G, Rosato R et al. Cancer mortality reduction and metformin. A retrospective cohort study in type 2 diabetic patients. Diabetes Obes Metab 2011 Aug 3. [Epub ahead of print]</mixed-citation><mixed-citation xml:lang="en">Bo S, Ciccone G, Rosato R et al. Cancer mortality reduction and metformin. A retrospective cohort study in type 2 diabetic patients. Diabetes Obes Metab 2011 Aug 3. [Epub ahead of print]</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Bosco JL, Antonsen S, Sørensen HT et al. Metformin and incident breast cancer among diabetic women: a population-based case-control study in Denmark. Cancer Epidemiol Biomarkers Prev 2011;20(1):101-111.</mixed-citation><mixed-citation xml:lang="en">Bosco JL, Antonsen S, Sørensen HT et al. Metformin and incident breast cancer among diabetic women: a population-based case-control study in Denmark. Cancer Epidemiol Biomarkers Prev 2011;20(1):101-111.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Bruno RV, de Avila MA, Neves FB et al. Comparison of two doses of metformin (2.5 and 1.5 g/day) for the treatment of polycystic ovary syndrome and their effect on body mass index and waist circumference. Fertil Steril 2007;88(2):510-512.</mixed-citation><mixed-citation xml:lang="en">Bruno RV, de Avila MA, Neves FB et al. Comparison of two doses of metformin (2.5 and 1.5 g/day) for the treatment of polycystic ovary syndrome and their effect on body mass index and waist circumference. Fertil Steril 2007;88(2):510-512.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nature Reviews Cancer 2004;4:579-591.</mixed-citation><mixed-citation xml:lang="en">Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nature Reviews Cancer 2004;4:579-591.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Chong CR, Chabner BA. Mysterious metformin. Oncologist 2009;14(12):1178-1181.</mixed-citation><mixed-citation xml:lang="en">Chong CR, Chabner BA. Mysterious metformin. Oncologist 2009;14(12):1178-1181.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Christensen MM, Brasch-Andersen C, Green H, Nielsen F, Damkier P, Beck-Nielsen H, Brosen K. The pharmacogenetics of metformin and its impact on plasma metformin steady-state levels and glycosylated hemoglobin A1c. Pharmacogenet Genomics 2011;21(12):837-850.</mixed-citation><mixed-citation xml:lang="en">Christensen MM, Brasch-Andersen C, Green H, Nielsen F, Damkier P, Beck-Nielsen H, Brosen K. The pharmacogenetics of metformin and its impact on plasma metformin steady-state levels and glycosylated hemoglobin A1c. Pharmacogenet Genomics 2011;21(12):837-850.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Delahanty LM, Pan Q, Jablonski KA et al. Genetic Predictors of Weight Loss and Weight Regain After Intensive Lifestyle Modification, Metformin Treatment, or Standard Care in the Diabetes Prevention Program. Diabetes Care 2011 Dec 16. [Epub ahead of print]</mixed-citation><mixed-citation xml:lang="en">Delahanty LM, Pan Q, Jablonski KA et al. Genetic Predictors of Weight Loss and Weight Regain After Intensive Lifestyle Modification, Metformin Treatment, or Standard Care in the Diabetes Prevention Program. Diabetes Care 2011 Dec 16. [Epub ahead of print]</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Després JP. Potential contribution of metformin to the management of cardiovascular disease risk in patients withabdominal obesity, the metabolic syndrome and type 2 diabetes. Diabetes Metab 2003;29(4 Pt 2):6S53-6S61.</mixed-citation><mixed-citation xml:lang="en">Després JP. Potential contribution of metformin to the management of cardiovascular disease risk in patients withabdominal obesity, the metabolic syndrome and type 2 diabetes. Diabetes Metab 2003;29(4 Pt 2):6S53-6S61.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Dilman VM, Berstein LM, Yevtushenko TP. et al. Preliminary evidence on metabolic rehabilitation of cancer patients. Arch Geschwulstforsch 1988;58(3):175-183.</mixed-citation><mixed-citation xml:lang="en">Dilman VM, Berstein LM, Yevtushenko TP. et al. Preliminary evidence on metabolic rehabilitation of cancer patients. Arch Geschwulstforsch 1988;58(3):175-183.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Editorial. Cancer prevention with a diabetes pill? Science 2012;335:29.</mixed-citation><mixed-citation xml:lang="en">Editorial. Cancer prevention with a diabetes pill? Science 2012;335:29.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Evans JM, Donnelly LA, Emslie-Smith AM et al. Metformin and reduced risk of cancer in diabetic patients BMJ 2005; 30(7503):1304-1305.</mixed-citation><mixed-citation xml:lang="en">Evans JM, Donnelly LA, Emslie-Smith AM et al. Metformin and reduced risk of cancer in diabetic patients BMJ 2005; 30(7503):1304-1305.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Giovannucci E, Harlan DM, Archer MC et al. Diabetes and cancer: a consensus report. Diabetes Care 2010;(7):674-1685.</mixed-citation><mixed-citation xml:lang="en">Giovannucci E, Harlan DM, Archer MC et al. Diabetes and cancer: a consensus report. Diabetes Care 2010;(7):674-1685.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Goodwin PJ, Stambolic V. Obesity and insulin resistance in breast cancer-chemoprevention strategies with a focus on metformin. Breast 2011;3:S31-35.</mixed-citation><mixed-citation xml:lang="en">Goodwin PJ, Stambolic V. Obesity and insulin resistance in breast cancer-chemoprevention strategies with a focus on metformin. Breast 2011;3:S31-35.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Hadad S, Iwamoto T, Jordan L. et al. Evidence for biological effects of metformin in operable breast cancer: a pre-operative, window-of-opportunity, randomized trial. Breast Cancer Res Treat 2011;128(3):783-794.</mixed-citation><mixed-citation xml:lang="en">Hadad S, Iwamoto T, Jordan L. et al. Evidence for biological effects of metformin in operable breast cancer: a pre-operative, window-of-opportunity, randomized trial. Breast Cancer Res Treat 2011;128(3):783-794.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Home PD, Kahn SE, Jones NP. et al. Experience of malignancies with oral glucose-lowering drugs in the randomised controlled ADOPT (ADiabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials. Diabetologia 2010;53(9):1838-1845.</mixed-citation><mixed-citation xml:lang="en">Home PD, Kahn SE, Jones NP. et al. Experience of malignancies with oral glucose-lowering drugs in the randomised controlled ADOPT (ADiabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials. Diabetologia 2010;53(9):1838-1845.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Hosono K, Endo H, Takahashi H et al. Metformin suppresses colorectal aberrant crypt foci in a short-term clinical trial. Cancer Prev Res (Phila) 2010;3(9):1077-1083.</mixed-citation><mixed-citation xml:lang="en">Hosono K, Endo H, Takahashi H et al. Metformin suppresses colorectal aberrant crypt foci in a short-term clinical trial. Cancer Prev Res (Phila) 2010;3(9):1077-1083.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Leblanc ES, O&amp;amp;apos;Connor E, Whitlock EP et al. Effectiveness of primary care-relevant treatments for obesity in adults: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2011;155(7):434-447.</mixed-citation><mixed-citation xml:lang="en">Leblanc ES, O&amp;amp;apos;Connor E, Whitlock EP et al. Effectiveness of primary care-relevant treatments for obesity in adults: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2011;155(7):434-447.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Lee JH, Kim TI, Jeon SM et al. The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus. Int J Cancer 2011 Sep 12. [Epub ahead of print]</mixed-citation><mixed-citation xml:lang="en">Lee JH, Kim TI, Jeon SM et al. The effects of metformin on the survival of colorectal cancer patients with diabetes mellitus. Int J Cancer 2011 Sep 12. [Epub ahead of print]</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Lee MS, Hsu CC, Wahlqvist ML et al. Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals BMC Cancer 2011;11:20.</mixed-citation><mixed-citation xml:lang="en">Lee MS, Hsu CC, Wahlqvist ML et al. Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals BMC Cancer 2011;11:20.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Levri KM, Slaymaker E, Last A et al. Metformin as Treatment for Overweight and Obese Adults: A Systematic Review. Ann Fam Med 2005;3:457-461.</mixed-citation><mixed-citation xml:lang="en">Levri KM, Slaymaker E, Last A et al. Metformin as Treatment for Overweight and Obese Adults: A Systematic Review. Ann Fam Med 2005;3:457-461.</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Lew EA, Garfinkel L. Variations in mortality by weight among 750000 men and women. J. Chronic Dis 1979;32:563-576.</mixed-citation><mixed-citation xml:lang="en">Lew EA, Garfinkel L. Variations in mortality by weight among 750000 men and women. J. Chronic Dis 1979;32:563-576.</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Lugaro G, Giannattasio G. Effect of biguanides on the respiration of tumour cells. Experientia 1968;24(8):794-795.</mixed-citation><mixed-citation xml:lang="en">Lugaro G, Giannattasio G. Effect of biguanides on the respiration of tumour cells. Experientia 1968;24(8):794-795.</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Meneghini LF, Orozco-Beltran D, Khunti K. et al. Weight beneficial treatments for type 2 diabetes. J. Clin. Endocrinol. Metab 2011;96(11):3337-3353.</mixed-citation><mixed-citation xml:lang="en">Meneghini LF, Orozco-Beltran D, Khunti K. et al. Weight beneficial treatments for type 2 diabetes. J. Clin. Endocrinol. Metab 2011;96(11):3337-3353.</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">METFORMIN TRIALLISTS' COLLABORATION, Stevens R., McLellan J. et al. Cancer and all-cause mortality: meta-analysis of randomized clinical trials of metformin. ADA Meeting 2011;Abstr. 0950-P.</mixed-citation><mixed-citation xml:lang="en">METFORMIN TRIALLISTS' COLLABORATION, Stevens R., McLellan J. et al. Cancer and all-cause mortality: meta-analysis of randomized clinical trials of metformin. ADA Meeting 2011;Abstr. 0950-P.</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Moreno-Navarrete JM, Ortega FJ, Rodríguez-Hermosa JI et al. OCT1 expression in adipocytes could contribute to increased metformin action in obese subjects. Diabetes 2011;60(1):168-176.</mixed-citation><mixed-citation xml:lang="en">Moreno-Navarrete JM, Ortega FJ, Rodríguez-Hermosa JI et al. OCT1 expression in adipocytes could contribute to increased metformin action in obese subjects. Diabetes 2011;60(1):168-176.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Nieuwenhuis-Ruifrok AE, Kuchenbecker WK, Hoek A. et al. Insulin sensitizing drugs for weight loss in women of reproductive age who are overweight or obese: systematic review and meta-analysis. Hum Reprod Update 2009;15(1):57-68.</mixed-citation><mixed-citation xml:lang="en">Nieuwenhuis-Ruifrok AE, Kuchenbecker WK, Hoek A. et al. Insulin sensitizing drugs for weight loss in women of reproductive age who are overweight or obese: systematic review and meta-analysis. Hum Reprod Update 2009;15(1):57-68.</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Nobes JP, Langley SE, Klopper T et al. A prospective, randomized pilot study evaluating the effects of metformin and lifestyle intervention on patients with prostate cancer receiving androgen deprivation therapy. BJU Int. 2011 Sep 20. [Epub ahead of print]</mixed-citation><mixed-citation xml:lang="en">Nobes JP, Langley SE, Klopper T et al. A prospective, randomized pilot study evaluating the effects of metformin and lifestyle intervention on patients with prostate cancer receiving androgen deprivation therapy. BJU Int. 2011 Sep 20. [Epub ahead of print]</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Patel T, Hruby G, Badani K. et al. Clinical outcomes after radical prostatectomy in diabetic patients treated with metformin. Urology 2010;76(5):1240-1244.</mixed-citation><mixed-citation xml:lang="en">Patel T, Hruby G, Badani K. et al. Clinical outcomes after radical prostatectomy in diabetic patients treated with metformin. Urology 2010;76(5):1240-1244.</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Pedersen J. The effect of metformin on weight loss in obesity. Acta endocrinol. (Copenh.) 1965;49:479-486.</mixed-citation><mixed-citation xml:lang="en">Pedersen J. The effect of metformin on weight loss in obesity. Acta endocrinol. (Copenh.) 1965;49:479-486.</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Pollak M. Metformin and other biguanides in oncology: advancing the research agenda. Cancer Prev Res (Phila) 2010;3(9):1060-1065.</mixed-citation><mixed-citation xml:lang="en">Pollak M. Metformin and other biguanides in oncology: advancing the research agenda. Cancer Prev Res (Phila) 2010;3(9):1060-1065.</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Preventing cancer, cardiovascular disease, and diabetes: a common agenda for the American Cancer Society, the American Diabetes Association, and the American Heart Association. CA Cancer J. Clin 2004;54:190-207.</mixed-citation><mixed-citation xml:lang="en">Preventing cancer, cardiovascular disease, and diabetes: a common agenda for the American Cancer Society, the American Diabetes Association, and the American Heart Association. CA Cancer J. Clin 2004;54:190-207.</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Roginsky MS, Sandler J. Phenformin in human obesity. Ann N Y Acad Sci 1968;148(3):892-896.</mixed-citation><mixed-citation xml:lang="en">Roginsky MS, Sandler J. Phenformin in human obesity. Ann N Y Acad Sci 1968;148(3):892-896.</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Romero IL, McCormick A, McEwen KA et al. Relationship of Type II Diabetes and Metformin Use to Ovarian Cancer Progression, Survival, and Chemosensitivity. Obstet Gynecol 2012;119(1):61-67.</mixed-citation><mixed-citation xml:lang="en">Romero IL, McCormick A, McEwen KA et al. Relationship of Type II Diabetes and Metformin Use to Ovarian Cancer Progression, Survival, and Chemosensitivity. Obstet Gynecol 2012;119(1):61-67.</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Ruiter R, Visser LE, van Herk-Sukel MP et al. Lower Risk of Cancer in Patients on Metformin in Comparison With Those on Sulfonylurea Derivatives: Results from a large population-based follow-up study. Diabetes Care 2012;35(1):119-124.</mixed-citation><mixed-citation xml:lang="en">Ruiter R, Visser LE, van Herk-Sukel MP et al. Lower Risk of Cancer in Patients on Metformin in Comparison With Those on Sulfonylurea Derivatives: Results from a large population-based follow-up study. Diabetes Care 2012;35(1):119-124.</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Salpeter SR, Buckley NS, Kahn JA, Salpeter EE. Meta-analysis: metformin treatment in persons at risk for diabetes mellitus Am J Med 2008;121(2):149-157.</mixed-citation><mixed-citation xml:lang="en">Salpeter SR, Buckley NS, Kahn JA, Salpeter EE. Meta-analysis: metformin treatment in persons at risk for diabetes mellitus Am J Med 2008;121(2):149-157.</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 2010; 14(4):CD002967.</mixed-citation><mixed-citation xml:lang="en">Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev 2010; 14(4):CD002967.</mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">Segal ED, Yasmeen A, Beauchamp MC et al. Relevance of the OCT1 transporter to the antineoplastic effect of biguanides. Biochem Biophys Res Commun 2011 Oct 2. [Epub ahead of print]</mixed-citation><mixed-citation xml:lang="en">Segal ED, Yasmeen A, Beauchamp MC et al. Relevance of the OCT1 transporter to the antineoplastic effect of biguanides. Biochem Biophys Res Commun 2011 Oct 2. [Epub ahead of print]</mixed-citation></citation-alternatives></ref><ref id="cit58"><label>58</label><citation-alternatives><mixed-citation xml:lang="ru">Shin MJ, Hyun YJ, Kim OY. et al. Weight loss effect on inflammation and LDL oxidation in metabolically healthy but obese (MHO) individuals: low inflammation and LDL oxidation in MHO women. Int J Obes (Lond) 2006;30(10):1529-1534.</mixed-citation><mixed-citation xml:lang="en">Shin MJ, Hyun YJ, Kim OY. et al. Weight loss effect on inflammation and LDL oxidation in metabolically healthy but obese (MHO) individuals: low inflammation and LDL oxidation in MHO women. Int J Obes (Lond) 2006;30(10):1529-1534.</mixed-citation></citation-alternatives></ref><ref id="cit59"><label>59</label><citation-alternatives><mixed-citation xml:lang="ru">Srinivasan S, Ambler GR, Baur LA. et al. Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin. J Clin Endocrinol Metab 2006;91(6):2074-2080.</mixed-citation><mixed-citation xml:lang="en">Srinivasan S, Ambler GR, Baur LA. et al. Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin. J Clin Endocrinol Metab 2006;91(6):2074-2080.</mixed-citation></citation-alternatives></ref><ref id="cit60"><label>60</label><citation-alternatives><mixed-citation xml:lang="ru">Tannenbaum A, Silverstone H. Nutrition in relation to cancer. Adv Cancer Res 1953;1:451-501.</mixed-citation><mixed-citation xml:lang="en">Tannenbaum A, Silverstone H. Nutrition in relation to cancer. Adv Cancer Res 1953;1:451-501.</mixed-citation></citation-alternatives></ref><ref id="cit61"><label>61</label><citation-alternatives><mixed-citation xml:lang="ru">Vincent HK, Taylor AG. Biomarkers and potential mechanisms of obesity-induced oxidant stress in humans Int J Obes (Lond) 2006;30(3):400-418.</mixed-citation><mixed-citation xml:lang="en">Vincent HK, Taylor AG. Biomarkers and potential mechanisms of obesity-induced oxidant stress in humans Int J Obes (Lond) 2006;30(3):400-418.</mixed-citation></citation-alternatives></ref><ref id="cit62"><label>62</label><citation-alternatives><mixed-citation xml:lang="ru">Wild SH. Diabetes, treatments for diabetes and their effect on cancer incidence and mortality: attempts to disentangle the web of associations. Diabetologia 2011;54(7):1589-1592.</mixed-citation><mixed-citation xml:lang="en">Wild SH. Diabetes, treatments for diabetes and their effect on cancer incidence and mortality: attempts to disentangle the web of associations. Diabetologia 2011;54(7):1589-1592.</mixed-citation></citation-alternatives></ref><ref id="cit63"><label>63</label><citation-alternatives><mixed-citation xml:lang="ru">Yanovski JA, Krakoff J, Salaita CG et al. Effects of metformin on body weight and body composition in obese insulin-resistant children: a randomized clinical trial. Diabetes 2011; 60(2):477-485.</mixed-citation><mixed-citation xml:lang="en">Yanovski JA, Krakoff J, Salaita CG et al. Effects of metformin on body weight and body composition in obese insulin-resistant children: a randomized clinical trial. Diabetes 2011; 60(2):477-485.</mixed-citation></citation-alternatives></ref><ref id="cit64"><label>64</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang ZJ, Zheng ZJ, Kan H et al. Reduced Risk of Colorectal Cancer With Metformin Therapy in Patients With Type 2 Diabetes: A meta-analysis. Diabetes Care 2011;34(10):2323-2328.</mixed-citation><mixed-citation xml:lang="en">Zhang ZJ, Zheng ZJ, Kan H et al. Reduced Risk of Colorectal Cancer With Metformin Therapy in Patients With Type 2 Diabetes: A meta-analysis. Diabetes Care 2011;34(10):2323-2328.</mixed-citation></citation-alternatives></ref><ref id="cit65"><label>65</label><citation-alternatives><mixed-citation xml:lang="ru">Zhuang Y, Miskimins WK. Metformin induces both caspase-dependent and poly(ADP-ribose) polymerase-dependent cell death in breast cancer cells. Mol Cancer Res 2011;9(5):603-615.</mixed-citation><mixed-citation xml:lang="en">Zhuang Y, Miskimins WK. Metformin induces both caspase-dependent and poly(ADP-ribose) polymerase-dependent cell death in breast cancer cells. Mol Cancer Res 2011;9(5):603-615.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
