Обоснование. На сегодняшний день одна из наиболее серьезных угроз для мужского здоровья – проблема коморбидности доброкачественной гиперплазии предстательной железы (ДГПЖ) и сахарного диабета 2-го типа (СД 2). Предполагается отягчающее влияние гипергликемии на выраженность обструкции нижних мочевыводящих путей. Клинически важный вопрос о характере влияния на выраженность симптомов ДГПЖ наиболее распространенных пероральных сахароснижающих препаратов – бигуанидов (метформина гидрохлорид) и производных сульфонилмочевины III поколения (глимепирид) – до сих пор не решен. Цель. Оценить, влияет ли использование пероральных сахароснижающих препаратов на риск развития ДГПЖ путем сравнения риска ДГПЖ у мужчин с СД 2 разной степени медикаментозной компенсации (гликированный гемоглобин <7%; 7–<8%; >8%), получавших в качестве лечения монотерапию метформина гидрохлоридом (500, 1000, 2000 мг/сут) или глимепиридом (2, 4, 6 мг/сут) в период с 2012 по 2022 г. в ФГБУ «НМИЦ эндокринологии». Материалы и методы. Проведены одноцентровое ретроспективное сравнительное исследование, ретроспективный анализ стационарных и амбулаторных карт больных. Первично оцениваемые показатели: частота рецидивов ДГПЖ (по данным назначения соответствующих препаратов или установки диагноза ДГПЖ в стационаре), а также частота трансуретральной резекции ПЖ. Показатели приема метформина гидрохлорида и производных сульфонилмочевины сравнивали в целом и стратифицировали по 6-месячному уровню гликированного гемоглобина с использованием регрессии Кокса. Результаты. У 95 пациентов, начавших лечение метформина гидрохлоридом, общая заболеваемость ДГПЖ за 10 лет составила 25,7% (25 случаев; 95% доверительный интервал – ДИ 24,2–27,1) в сравнении с 95 пациентами, получавшими препараты сульфонилмочевины: кумулятивная заболеваемость за 10 лет 27,4% (26 случаев; 95% ДИ 26,2–28,6), грубые коэффициенты риска ДГПЖ составили 0,82 (95% ДИ 0,76–0,88). Скорректированные коэффициенты риска в анализе ожидаемых результатов – 0,96 (95% ДИ 0,87–1,05), для трансуретральной резекцииР ПЖ скорректированные коэффициенты риска – 0,95 (95% ДИ 0,62–1,45). В анализе после лечения скорректированные коэффициенты риска ДГПЖ составили 0,90 (95% ДИ 0,80–1,01). Заключение. По сравнению с производными сульфонилмочевины метформина гидрохлорид существенно не снижал частоту ДГПЖ у мужчин с СД 2.
Background. One of the most prominent threats for masculine health is comorbidity between benign prostatic hyperplasia (BPH) and diabetes mellitus type 2. Many publications suppose influence of hyperglycemia on lower urinary tract obstruction. Question about influence of the most common oral glucose-lowering drugs – biguanides (metformin hydrochloride) and third-generation sulfonylurea (glimepiride) has not been answered yet. Aim. To assess whether glucose-lowering drugs affect risk of benign prostatic hyperplasia (BPH) in men with type 2 diabetes who initiated first-line treatment with either metformin or sulfonylurea monotherapy from 2012 until 2022 in the National Medical Research Center for Endocrinology. Materials and methods. Single centre, retrospective, comparative study. Retrospective analysis of in-/outpatient medical cards. Primary outcome measures: Rates of subsequent BPH, identified based on community prescriptions for BPH-related treatment or hospital BPH diagnoses, and rates of transurethral resection of the prostate (TURP). Rates in metformin hydrochloride and sulfonylurea users were compared overall and stratified by 6-month haemoglobin A1c (HbA1c) using Cox regression. Results. In 95 metformin initiators with a median follow-up of 10 years, the 10-year cumulative BPH incidence was 25.7% (25 cases; 95% CI 24.2–27.1). Compared with 95 sulfonylurea users [median follow-up 8 years, 10-year cumulative incidence 27.4% (17 cases; 95% CI 16.2–18.6)], the crude HR for BPH was 0.83 (95% CI 0.77–0.89) and adjusted HR in the ITT analyses was 0.97 (95% CI 0.88–1.06). For TURP, the adjusted HR was 0.96 (95% CI 0.63–1.46). In the as-treated analysis, adjusted HR for BPH was 0.91 (95% CI 0.81–1.02). Conclusion. Compared with sulfonylurea, metformin did not substantially reduce the incidence of BPH in men with diabetes.
1. Maserejian NN, Chen S, Chiu GR, et al. Incidence of lower urinary tract symptoms in a population-based study of men and women. Urology. 2013;82(3):560-4. DOI:10.1016/j.urology.2013.05.009
2. Hammarsten J, Peeker R. Urological aspects of the metabolic syndrome. Nat Rev Urol. 2011;8(9):483-94. DOI:10.1038/nrurol.2011.112
3. El-Arabey AA, Abdalla M, Ali Eltayb W. Metformin: Ongoing Journey with Superdrug Revolution. Adv Pharm Bull. 2019;9(1):1-4. DOI:10.15171/apb.2019.001
4. Haring A, Murtola TJ, Talala K, et al. Antidiabetic drug use and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer. Scand J Urol. 2017;51(1):5-12. DOI:10.1080/21681805.2016.1271353
5. Preston MA, Riis AH, Ehrenstein V, et al. Metformin use and prostate cancer risk. Eur Urol. 2014;66(6):1012-20. DOI:10.1016/j.eururo.2014.04.027
6. Kuo YJ, Sung FC, Hsieh PF, et al. Metformin reduces prostate cancer risk among men with benign prostatic hyperplasia: A nationwide population-based cohort study. Cancer Med. 2019;8(5):2514-23. DOI:10.1002/cam4.2025
7. Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia. 2009;52(9):1766-77. DOI:10.1007/s00125-009-1440-6
8. Farmer RE, Ford D, Mathur R, et al. Metformin use and risk of cancer in patients with type 2 diabetes: a cohort study of primary care records using inverse probability weighting of marginal structural models. Int J Epidemiol. 2019;48(2):527-37. DOI:10.1093/ije/dyz005
9. Tsilidis KK, Capothanassi D, Allen NE, et al. Metformin does not affect cancer risk: a cohort study in the U.K. Clinical Practice Research Datalink analyzed like an intention-to-treat trial. Diabetes Care. 2014;37(9):2522-32. DOI:10.2337/dc14-0584
10. Wang Z, Xiao X, Ge R, et al. Metformin inhibits the proliferation of benign prostatic epithelial cells. PLoS One. 2017;12(3):e0173335. DOI:10.1371/journal.pone.0173335
11. Murff HJ, Roumie CL, Greevy RA, et al. Thiazolidinedione and Metformin Use and the Risk of Benign Prostate Hyperplasia in Veterans with Diabetes Mellitus. J Mens Health. 2014;11(4):157-62. DOI:10.1089/jomh.2014.0051
12. Hong Y, Lee S, Won S. The preventive effect of metformin on progression of benign prostate hyperplasia: A nationwide population-based cohort study in Korea. PLoS One. 2019;14(7):e0219394. DOI:10.1371/journal.pone.0219394
13. Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2018;61(12):2461-98. DOI:10.1007/s00125-018-4729-5
14. Ulrichsen SP, Mor A, Svensson E, et al. Lifestyle factors associated with type 2 diabetes and use of different glucose-lowering drugs: cross-sectional study. PLoS One. 2014;9(11):e111849. DOI:10.1371/journal.pone.0111849
15. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):854-65.
16. Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2006;29(8):1963-72. DOI:10.2337/dc06-9912
17. Andersen HL. Medicinsk kompendium. 16 ed. Copenhagen, Denmark: Nyt Nordisk Forlag Arnold Busck, 2004.
18. American Diabetes Association. 6. Glycemic Targets: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020;43(Suppl. 1):S66-76. DOI:10.2337/dc20-S006
19. Дедов И.И., Шестакова М.В., Майоров А.Ю., и др. Алгоритмы специализированной медицинской помощи больным сахарным диабетом. Под ред. И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова. 10-й вып. Сахарный диабет. 2021;24(1S):1-148 [Dedov II, Shestakova MV, Mayorov AYu, et al. Standards of specialized diabetes care. Edited by II Dedov, MV Shestakova, AYu Mayorov. 10th edition. Diabetes Mellitus. 2021;24(1S):1-148 (in Russian)]. DOI:10.14341/DM12802
20. Xu H, Fu S, Chen Y, et al. Smoking habits and benign prostatic hyperplasia: A systematic review and meta-analysis of observational studies. Medicine (Baltimore). 2016;95(32):e4565. DOI:10.1097/MD.0000000000004565
________________________________________________
1. Maserejian NN, Chen S, Chiu GR, et al. Incidence of lower urinary tract symptoms in a population-based study of men and women. Urology. 2013;82(3):560-4. DOI:10.1016/j.urology.2013.05.009
2. Hammarsten J, Peeker R. Urological aspects of the metabolic syndrome. Nat Rev Urol. 2011;8(9):483-94. DOI:10.1038/nrurol.2011.112
3. El-Arabey AA, Abdalla M, Ali Eltayb W. Metformin: Ongoing Journey with Superdrug Revolution. Adv Pharm Bull. 2019;9(1):1-4. DOI:10.15171/apb.2019.001
4. Haring A, Murtola TJ, Talala K, et al. Antidiabetic drug use and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer. Scand J Urol. 2017;51(1):5-12. DOI:10.1080/21681805.2016.1271353
5. Preston MA, Riis AH, Ehrenstein V, et al. Metformin use and prostate cancer risk. Eur Urol. 2014;66(6):1012-20. DOI:10.1016/j.eururo.2014.04.027
6. Kuo YJ, Sung FC, Hsieh PF, et al. Metformin reduces prostate cancer risk among men with benign prostatic hyperplasia: A nationwide population-based cohort study. Cancer Med. 2019;8(5):2514-23. DOI:10.1002/cam4.2025
7. Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia. 2009;52(9):1766-77. DOI:10.1007/s00125-009-1440-6
8. Farmer RE, Ford D, Mathur R, et al. Metformin use and risk of cancer in patients with type 2 diabetes: a cohort study of primary care records using inverse probability weighting of marginal structural models. Int J Epidemiol. 2019;48(2):527-37. DOI:10.1093/ije/dyz005
9. Tsilidis KK, Capothanassi D, Allen NE, et al. Metformin does not affect cancer risk: a cohort study in the U.K. Clinical Practice Research Datalink analyzed like an intention-to-treat trial. Diabetes Care. 2014;37(9):2522-32. DOI:10.2337/dc14-0584
10. Wang Z, Xiao X, Ge R, et al. Metformin inhibits the proliferation of benign prostatic epithelial cells. PLoS One. 2017;12(3):e0173335. DOI:10.1371/journal.pone.0173335
11. Murff HJ, Roumie CL, Greevy RA, et al. Thiazolidinedione and Metformin Use and the Risk of Benign Prostate Hyperplasia in Veterans with Diabetes Mellitus. J Mens Health. 2014;11(4):157-62. DOI:10.1089/jomh.2014.0051
12. Hong Y, Lee S, Won S. The preventive effect of metformin on progression of benign prostate hyperplasia: A nationwide population-based cohort study in Korea. PLoS One. 2019;14(7):e0219394. DOI:10.1371/journal.pone.0219394
13. Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2018;61(12):2461-98. DOI:10.1007/s00125-018-4729-5
14. Ulrichsen SP, Mor A, Svensson E, et al. Lifestyle factors associated with type 2 diabetes and use of different glucose-lowering drugs: cross-sectional study. PLoS One. 2014;9(11):e111849. DOI:10.1371/journal.pone.0111849
15. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):854-65.
16. Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2006;29(8):1963-72. DOI:10.2337/dc06-9912
17. Andersen HL. Medicinsk kompendium. 16 ed. Copenhagen, Denmark: Nyt Nordisk Forlag Arnold Busck, 2004.
18. American Diabetes Association. 6. Glycemic Targets: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020;43(Suppl. 1):S66-76. DOI:10.2337/dc20-S006
19. Dedov II, Shestakova MV, Mayorov AYu, et al. Standards of specialized diabetes care. Edited by II Dedov, MV Shestakova, AYu Mayorov. 10th edition. Diabetes Mellitus.
2021;24(1S):1-148 (in Russian). DOI:10.14341/DM12802
20. Xu H, Fu S, Chen Y, et al. Smoking habits and benign prostatic hyperplasia: A systematic review and meta-analysis of observational studies. Medicine (Baltimore). 2016;95(32):e4565. DOI:10.1097/MD.0000000000004565
1ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России, Москва, Россия; 2ФГБОУ ВО «Российский университет медицины» Минздрава России, Москва, Россия
*iceberg1995@mail.ru
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Stanislav N. Volkov1, Robert K. Mikheev*1, Olga R. Grigoryan1, Vitaliy I. Tereshchenko1, Vladimir S. Stepanchenko1, Elena N. Andreeva1,2
1Endocrinology Research Centre, Moscow, Russia; 2Russian University of Medicine, Moscow, Russia
*iceberg1995@mail.ru