endofocusFOCUS ЭндокринологияFOCUS. Endocrinology2713-01772713-0185ООО "Издательство "Перо"10.62751/2713-0177-2026-7-2-06endofocus-211Research ArticleОБЗОРЫСкрытые возможности профилактики сердечной недостаточности: роль терапии фенофибратомHidden opportunities for the prevention of heart failure: The role of fenofibrate therapythttps://orcid.org/0000-0002-8505-1848ГиляревскийС. Р.GilyarevskyS. R.

Гиляревский Сергей Руджерович – д.м.н., профессор

125284, Москва, 2-й Боткинский проезд, влад. 5 

RESEARCH ID: AAN-4179-2021 

Sergey R. Gilyarevsky – Dr. Sci. (Med.), professor  

5/2 Botkinskiy Drive, Moscow, 125284 

RESEARCH ID: AAN-4179-2021 

sgilarevsky@rambler.ruМосковский многопрофильный научно-клинический центр им. С.П. Боткина; Российский геронтологический научно-клинический центр, Российский национальный исследовательский медицинский университет им. Н.И. Пирогова (Пироговский университет); Российская медицинская академия непрерывного профессионального образованияРоссияS.P. Botkin Moscow Multidisciplinary Research and Clinical Center; Russian Gerontology Clinical Research Center – Pirogov Russian National Research Medical University; Russian Medical Academy of Continuous Professional EducationRussian Federation202611072026724145Copyright © Гиляревский С.Р., 20262026Гиляревский С.Р.Gilyarevsky S.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://endofocus.elpub.ru/jour/article/view/211

Статья посвящена анализу доказательных данных, свидетельствующих о возможности дополнительного снижения риска развития сердечной недостаточности (СН) и ее прогрессирования у пациентов с сахарным диабетом 2-го типа (СД2) и дислипидемией за счет применения фенофибрата. Рассматривается актуальность проблемы уменьшения остаточного риска осложнений СН у коморбидных больных СД2. Приводятся результаты как клинических, так и экспериментальных исследований, в которых установлено положительное влияние фенофибрата, являющегося агонистом рецепторов, активируемых пролифераторами пероксисом, альфа (PPARα), на риск развития и прогрессирования СН, обсуждаются возможные механизмы реализации такого эффекта препарата. Приводятся данные об отличиях терапевтического действия фенофибрата от другого представителя фибратов, которые определяют актуальность его применения в клинической практике. 

The article discusses evidence-based data indicating the potential for additional reduction of the risk of developing heart failure (HF) and its progression in patients with type 2 diabetes mellitus (T2DM) and dyslipidemia through the use of fenofibrate. The relevance of reducing the residual risk of heart failure–related complications in patients with T2DM is considered. Results of both clinical and experimental studies are presented, demonstrating a beneficial effect of fenofibrate, an agonist of peroxisome proliferator–activated receptor alpha (PPARα), on the risk of HF development and progression. Possible mechanisms underlying the beneficial effects of fenofibrate are discussed, which may account for its impact on the risk of HF progression in patients with T2DM. Data are provided on differences between the effects of fenofibrate and those of another representative of the fibrate class, supporting the relevance of its use in clinical practice. 

сахарный диабет 2-го типадислипидемиясердечная недостаточностьфенофибратtype 2 diabetes mellitusdyslipidemiaheart failurefenofibratReferencesGreene SJ, Xu H, Chiswell K, Felker GM, Lewsey SC, Divanji PH, et al. One-year outcomes in patients hospitalized for heart failure with reduced ejection fraction prescribed quadruple medical therapy at discharge. JAMA Cardiol. 2026;11(3):293–97. https://doi.org/10.1001/jamacardio.2025.5339Greene SJ, Xu H, Chiswell K, Felker GM, Lewsey SC, Divanji PH, et al. One-year outcomes in patients hospitalized for heart failure with reduced ejection fraction prescribed quadruple medical therapy at discharge. JAMA Cardiol. 2026;11(3):293–97. https://doi.org/10.1001/jamacardio.2025.5339van Essen BJ, Ceelen DCH, Ouwerkerk W, Teng TK, Tharshana GN, Hew FM, et al. Pharmacologic treatment of heart failure with reduced ejection fraction: An updated systematic review and network meta-analysis. J Am Coll Cardiol. 2025;86(24):2513–26. https://doi.org/10.1016/j.jacc.2025.08.054van Essen BJ, Ceelen DCH, Ouwerkerk W, Teng TK, Tharshana GN, Hew FM, et al. Pharmacologic treatment of heart failure with reduced ejection fraction: An updated systematic review and network meta-analysis. J Am Coll Cardiol. 2025;86(24):2513–26. https://doi.org/10.1016/j.jacc.2025.08.054McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, et al.; ESC Scientific Document Group. 2023 focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023;44(37):3627–39. https://doi.org/10.1093/eurheartj/ehad195McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, et al.; ESC Scientific Document Group. 2023 focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023;44(37):3627–39. https://doi.org/10.1093/eurheartj/ehad195Solomon SD, McMurray JJV, Vaduganathan M, Claggett B, Jhund PS, Desai AS, et al.; or preserved ejection fraction. N Engl J Med. 2024;391(16):1475– 85. https://doi.org/10.1056/NEJMoa2407107Solomon SD, McMurray JJV, Vaduganathan M, Claggett B, Jhund PS, Desai AS, et al.; or preserved ejection fraction. N Engl J Med. 2024;391(16):1475– 85. https://doi.org/10.1056/NEJMoa2407107Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: The Framingham study. Am J Cardiol. 1974;34(1):29–34. https://doi.org/10.1016/0002-9149(74)90089-7Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: The Framingham study. Am J Cardiol. 1974;34(1):29–34. https://doi.org/10.1016/0002-9149(74)90089-7Noumegni SR, Kaze AD, Bertoni AG, Fonarow GC, Echouffo-Tcheugui JB. Diabetes, functional status, and mortality in chronic heart failure. Diabetes Care. 2024;47(11):e88–e89. https://doi.org/10.2337/dc24-1586Noumegni SR, Kaze AD, Bertoni AG, Fonarow GC, Echouffo-Tcheugui JB. Diabetes, functional status, and mortality in chronic heart failure. Diabetes Care. 2024;47(11):e88–e89. https://doi.org/10.2337/dc24-1586Ferreira JP, Vasques-Novoa F, Ferrao D, Saraiva F, Falcao-Pires I, Neves JS, et al. Fenofibrate and heart failure outcomes in patients with type 2 diabetes: Analysis from ACCORD. Diabetes Care. 2022;45(7):1584–91. https://doi.org/10.2337/dc21-1977Ferreira JP, Vasques-Novoa F, Ferrao D, Saraiva F, Falcao-Pires I, Neves JS, et al. Fenofibrate and heart failure outcomes in patients with type 2 diabetes: Analysis from ACCORD. Diabetes Care. 2022;45(7):1584–91. https://doi.org/10.2337/dc21-1977Kim JY, Kim NH, Lee J, Kim DH, Kim SG. Fenofibrate therapy and risk of heart failure outcomes in patients with Type 2 diabetes: A propensity-matched cohort study. Eur Heart J Cardiovasc Pharmacother. 2025;11(7):620–29. https://doi.org/10.1093/ehjcvp/pvaf053Kim JY, Kim NH, Lee J, Kim DH, Kim SG. Fenofibrate therapy and risk of heart failure outcomes in patients with Type 2 diabetes: A propensity-matched cohort study. Eur Heart J Cardiovasc Pharmacother. 2025;11(7):620–29. https://doi.org/10.1093/ehjcvp/pvaf053Hida Y, Imamura T, Kinugawa K. Pemafibrate and cardiac reverse remodeling in patients with systolic heart failure receiving guideline-directed medical therapy. J Cardiol Cases. 2024;31(2):42–45. https://doi.org/10.1016/j.jccase.2024.10.001Hida Y, Imamura T, Kinugawa K. Pemafibrate and cardiac reverse remodeling in patients with systolic heart failure receiving guideline-directed medical therapy. J Cardiol Cases. 2024;31(2):42–45. https://doi.org/10.1016/j.jccase.2024.10.001Das Pradhan A, Glynn RJ, Fruchart JC, MacFadyen JG, Zaharris ES, Everett BM, et al.; PROMINENT Investigators. Triglyceride lowering with pemafibrate to reduce cardiovascular risk. N Engl J Med. 2022;387(21):1923–34. https://doi.org/10.1056/NEJMoa2210645Das Pradhan A, Glynn RJ, Fruchart JC, MacFadyen JG, Zaharris ES, Everett BM, et al.; PROMINENT Investigators. Triglyceride lowering with pemafibrate to reduce cardiovascular risk. N Engl J Med. 2022;387(21):1923–34. https://doi.org/10.1056/NEJMoa2210645d'Emden MC, Jenkins AJ, Li L, Zannino D, Mann KP, Best JD, et al.; FIELD Study Investigators. Favourable effects of fenofibrate on lipids and cardiovascular disease in women with type 2 diabetes: Results from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetologia. 2014;57(11):2296–303. https://doi.org/10.1007/s00125-014-3344-3d'Emden MC, Jenkins AJ, Li L, Zannino D, Mann KP, Best JD, et al.; FIELD Study Investigators. Favourable effects of fenofibrate on lipids and cardiovascular disease in women with type 2 diabetes: Results from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetologia. 2014;57(11):2296–303. https://doi.org/10.1007/s00125-014-3344-3Arai H, Yamashita S, Yokote K, Araki E, Suganami H, Ishibashi S; K-877 Study Group. Efficacy and safety of pemafibrate versus fenofibrate in patients with high triglyceride and low HDL cholesterol levels: A multicenter, placebo-controlled, double-blind, randomized trial. J Atheroscler Thromb. 2018;25(6):521–38. https://doi.org/10.5551/jat.44412Arai H, Yamashita S, Yokote K, Araki E, Suganami H, Ishibashi S; K-877 Study Group. Efficacy and safety of pemafibrate versus fenofibrate in patients with high triglyceride and low HDL cholesterol levels: A multicenter, placebo-controlled, double-blind, randomized trial. J Atheroscler Thromb. 2018;25(6):521–38. https://doi.org/10.5551/jat.44412Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, et al.; FIELD study investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): Randomised controlled trial. Lancet. 2005;366(9500):1849–61. https://doi.org/10.1016/S0140-6736(05)67667-2Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, et al.; FIELD study investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): Randomised controlled trial. Lancet. 2005;366(9500):1849–61. https://doi.org/10.1016/S0140-6736(05)67667-2Liu M, Lim ST, Song W, Coffman TM, Wang X. Beyond lipids: Fenofibrate in diabetic retinopathy and nephropathy. Trends Pharmacol Sci. 2026;47(3):325–41. https://doi.org/10.1016/j.tips.2025.07.014Liu M, Lim ST, Song W, Coffman TM, Wang X. Beyond lipids: Fenofibrate in diabetic retinopathy and nephropathy. Trends Pharmacol Sci. 2026;47(3):325–41. https://doi.org/10.1016/j.tips.2025.07.014Liu X, Zhang J, Zhou W, Liu J, Wang Y. Effect of fenofibrate on blood lipid, sICAM-1, ET-1 and prognosis in chronic heart failure patients complicated with diabetes. Cell Mol Biol (Noisy-le-grand). 2023;69(2):110–14. https://doi.org/10.14715/cmb/2023.69.2.18Liu X, Zhang J, Zhou W, Liu J, Wang Y. Effect of fenofibrate on blood lipid, sICAM-1, ET-1 and prognosis in chronic heart failure patients complicated with diabetes. Cell Mol Biol (Noisy-le-grand). 2023;69(2):110–14. https://doi.org/10.14715/cmb/2023.69.2.18Neubauer S. The failing heart – an engine out of fuel. N Engl J Med. 2007;356(11):1140–51. https://doi.org/10.1056/NEJMra063052Neubauer S. The failing heart – an engine out of fuel. N Engl J Med. 2007;356(11):1140–51. https://doi.org/10.1056/NEJMra063052 17. Li X, Bi X. Integrated control of fatty acid metabolism in heart failure. Metabolites. 2023;13(5):615. https://doi.org/10.3390/metabo13050615Li X, Bi X. Integrated control of fatty acid metabolism in heart failure. Metabolites. 2023;13(5):615. https://doi.org/10.3390/metabo13050615Flavell DM, Wootton PT, Myerson SG, World MJ, Pennell DJ, Humphries SE, et al. Variation in the lipoprotein lipase gene influences exercise-induced left ventricular growth. J Mol Med (Berl). 2006;84(2):126–31. https://doi.org/10.1007/s00109-005-0002-8Flavell DM, Wootton PT, Myerson SG, World MJ, Pennell DJ, Humphries SE, et al. Variation in the lipoprotein lipase gene influences exercise-induced left ventricular growth. J Mol Med (Berl). 2006;84(2):126–31. https://doi.org/10.1007/s00109-005-0002-8Kaimoto S, Hoshino A, Ariyoshi M, Okawa Y, Tateishi S, Ono K, et al. Activation of PPAR-α in the early stage of heart failure maintained myocardial function and energetics in pressure-overload heart failure. Am J Physiol Heart Circ Physiol. 2017;312(2):H305–H313. https://doi.org/10.1152/ajpheart.00553.2016Kaimoto S, Hoshino A, Ariyoshi M, Okawa Y, Tateishi S, Ono K, et al. Activation of PPAR-α in the early stage of heart failure maintained myocardial function and energetics in pressure-overload heart failure. Am J Physiol Heart Circ Physiol. 2017;312(2):H305–H313. https://doi.org/10.1152/ajpheart.00553.2016Dong Z, Zhao P, Xu M, Zhang C, Guo W, Chen H, et al. Astragaloside IV alleviates heart failure via activating PPARα to switch glycolysis to fatty acid β-oxidation. Sci Rep. 2017;7(1):2691. https://doi.org/10.1038/s41598-017-02360-5Dong Z, Zhao P, Xu M, Zhang C, Guo W, Chen H, et al. Astragaloside IV alleviates heart failure via activating PPARα to switch glycolysis to fatty acid β-oxidation. Sci Rep. 2017;7(1):2691. https://doi.org/10.1038/s41598-017-02360-5Wei H, Yin M, Chang J, Feng B, Zhou Q, Li X, et al. Empagliflozin's cardioenergetic protective effects through PPARα pathway modulation in heart failure. Front Pharmacol. 2025;16:1636810. https://doi.org/10.3389/fphar.2025.1636810Wei H, Yin M, Chang J, Feng B, Zhou Q, Li X, et al. Empagliflozin's cardioenergetic protective effects through PPARα pathway modulation in heart failure. Front Pharmacol. 2025;16:1636810. https://doi.org/10.3389/fphar.2025.1636810Handford C, Stirling-Barros L, Ganji-Arjenaki M, Mahmod M, Nazarzadeh M, Wamil M. Targeting cardiac metabolism in heart failure with PPARα agonists: A review of preclinical and clinical evidence. Biomedicines. 2025;13(9):2080. https://doi.org/10.3390/biomedicines13092080Handford C, Stirling-Barros L, Ganji-Arjenaki M, Mahmod M, Nazarzadeh M, Wamil M. Targeting cardiac metabolism in heart failure with PPARα agonists: A review of preclinical and clinical evidence. Biomedicines. 2025;13(9):2080. https://doi.org/10.3390/biomedicines13092080Park J, Song H, Moon S, Kim Y, Cho S, Han K, et al. Cardiometabolic benefits of fenofibrate in heart failure related to obesity and diabetes. Cardiovasc Diabetol. 2024;23(1):343. https://doi.org/10.1186/s12933-024-02417-6Park J, Song H, Moon S, Kim Y, Cho S, Han K, et al. Cardiometabolic benefits of fenofibrate in heart failure related to obesity and diabetes. Cardiovasc Diabetol. 2024;23(1):343. https://doi.org/10.1186/s12933-024-02417-6Dhyani N, Saidullah B, Fahim M, Omanwar S. Fenofibrate ameliorates neural, mechanical, chemical, and electrical alterations in the murine model of heart failure. Hum Exp Toxicol. 2019;38(10):1183–94. https://doi. org/10.1177/0960327119860173Dhyani N, Saidullah B, Fahim M, Omanwar S. Fenofibrate ameliorates neural, mechanical, chemical, and electrical alterations in the murine model of heart failure. Hum Exp Toxicol. 2019;38(10):1183–94. https://doi.org/10.1177/0960327119860173Pitt B, Vaidya A. Mineralocorticoid receptor antagonist use in hypertension to prevent heart failure. JACC Heart Fail. 2025;13(12):102452. https://doi.org/10.1016/j.jchf.2025.02.021Pitt B, Vaidya A. Mineralocorticoid receptor antagonist use in hypertension to prevent heart failure. JACC Heart Fail. 2025;13(12):102452. https://doi.org/10.1016/j.jchf.2025.02.021Thuzar M, Stowasser M. The mineralocorticoid receptor-an emerging player in metabolic syndrome? J Hum Hypertens. 2021;35(2):117–23. https://doi.org/10.1038/s41371-020-00467-3Thuzar M, Stowasser M. The mineralocorticoid receptor-an emerging player in metabolic syndrome? J Hum Hypertens. 2021;35(2):117–23. https://doi.org/10.1038/s41371-020-00467-3Lebrasseur NK, Duhaney TA, De Silva DS, Cui L, Ip PC, Joseph L, Sam F. Effects of fenofibrate on cardiac remodeling in aldosterone-induced hypertension. Hypertension. 2007;50(3):489–96. https://doi.org/10.1161/HYPERTENSIONAHA.107.092403Lebrasseur NK, Duhaney TA, De Silva DS, Cui L, Ip PC, Joseph L, Sam F. Effects of fenofibrate on cardiac remodeling in aldosterone-induced hypertension. Hypertension. 2007;50(3):489–96. https://doi.org/10.1161/HYPERTENSIONAHA.107.092403Huang WP, Yin WH, Chen JS, Huang PH, Chen JW, Lin SJ. Fenofibrate reverses dysfunction of EPCs caused by chronic heart failure. J Cardiovasc Transl Res. 2020;13(2):158–70. https://doi.org/10.1007/s12265-019-09889-yHuang WP, Yin WH, Chen JS, Huang PH, Chen JW, Lin SJ. Fenofibrate reverses dysfunction of EPCs caused by chronic heart failure. J Cardiovasc Transl Res. 2020;13(2):158–70. https://doi.org/10.1007/s12265-019-09889-yHuang WP, Yin WH, Chen JS, Huang PH, Chen JW, Lin SJ. Fenofibrate attenuates doxorubicin-induced cardiac dysfunction in mice via activating the eNOS/EPC pathway. Sci Rep. 2021;11(1):1159. https://doi.org/10.1038/s41598-021-80984-4.Huang WP, Yin WH, Chen JS, Huang PH, Chen JW, Lin SJ. Fenofibrate attenuates doxorubicin-induced cardiac dysfunction in mice via activating the eNOS/EPC pathway. Sci Rep. 2021;11(1):1159. https://doi.org/10.1038/s41598-021-80984-4.Huang WP, Yin WH, Chen JS, Huang PH, Chen JW, Lin SJ. Fenofibrate attenuates doxorubicin-induced cardiac dysfunction in mice via activating the eNOS/EPC pathway. Sci Rep. 2021;11(1):1159. https://doi.org/10.1038/s41598-021-80984-4.

The authors declare that there are no conflicts of interest present.