Журнал кардиореспираторных исследований 2025. №1

Subject of the article

REVIEW OF CLINICAL TRIALS WITH SODIUM GLUCOSE COTRANSPORTER TYPE 2 INHIBITORS (23-28)

Authors

Akhmedova D.T., Alimova D.A., Trigulova R.Kh.

Institution

Republican Specialized Scientific and Practical Medical Center of Cardiology

Abstract

This review article summarizes and analyzes clinical trials assessing the efficacy and safety of SGLT2 inhibitors, a class of drugs used primarily for the treatment of Type 2 diabetes mellitus. The review covers several key studies, including the EMMY, EMPAREG OUTCOME, DAPA-HF, EMPULSE, SOLOIST-WHF and EMPACT-MI trials, highlighting the positive impact of SGLT2 inhibitors on reducing cardiovascular events and improving kidney outcomes. The article further discusses the expansion of SGLT2 inhibitors' use beyond diabetes treatment to address heart failure and chronic kidney disease. The authors conclude that SGLT2 inhibitors offer significant benefits in managing type 2 diabetes mellitus and related complications, while also demonstrating promise in broader therapeutic areas. This review is essential for understanding the evolving role of SGLT2 inhibitors in modern clinical practice and provides valuable insights into ongoing research. It is particularly relevant to my study on the cardiovascular benefits of medications and their long-term effects.

Key words

SGLT2 inhibitors, antiremodeling effect, heart failure, myocardial infarction, chronic kidney disease, glomerular filtration rate, antihyperglycemic effect

Literature

1. Bagriy A.E., Efremenko V. A., Golodnikov I.A., Druzhinkina N.V., Trandafilova M.N. Federal state budgetary educational institution of high school donetsk state medical university named after m. Gorky moh rf department of internal medicine no. 2. P-1-2. 2. N.A. Shumilova, S.I. Pavlova Acta medicine Eurasica. 2019. No. 1 UDC 615.272.3 BBK 52.81 http://acta-medica- eurasica.ru/single/2019/1 3. Mkrtumyan A.M., Egshatyan L.E. New non-insulin-dependent approach to the treatment of type 2 diabetes mellitus. Dapagliflozin: results of clinical trials // Effective pharmacotherapy. 2015. No. 11. P. 17–25. 4. Shestakova M.V., Sukhareva O.Yu. Gliflozins: features of hypoglycemic action and non-glycemic effects of a new class of drugs // Clinical Pharmacology and Therapy. 2016. Vol. 25, No. 2. P. 65–71. 5. Rieg T., Vallon V. Development of SGLT1 and SGLT2 inhibitors. Diabetologia, 2018, vol. 61, P. 2079–2086. 6. Scheen A. Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment // Drugs. 2015. Vol. 75. No. 1. P. 33–59. 7. Ferrannini E., Muscelli E., Frascerra S. et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients // J. Clin. Invest. 2014. Vol. 124. No. 2. P. 499–508. 8. Tripolt NJ, Kolesnik E, Pferschy PN, Verheyen N, Ablasser K, Sailer S, et al. Impact of EMpagliflozin on cardiac function and biomarkers of heart failure in patients with acute MYocardial infarction—the EMMYtrial. American Heart Journal.2020; 221: P 39–47. 9. Von Lewinski D, Kolesnik E, Tripolt NJ, Pferschy PN, Benedikt M, Wallner M, et al. Empagliflozin in acute myocardial infarctiontion: the EMMY trial. European Heart Journal. 2022; 43: P 4421-4432. 10. Martin Benedikt, Ewald Kolesnik, Harald Sourij, Dirk von Lewinski. SGLT2 Inhibition in Acute Myocardial Infarction—A Comprehensive Review. Rev. Cardiovasc. Med. 2023, 24(2), P 32. https://doi.org/10.31083/j.rcm2402032 11. Lecour S, Andreadou I, Bøtker HE, Davidson SM, Heusch G, Ruiz- Meana M et al . Iimproving Preclinical Assessment of Car dioprotective Therapies (IMPACT) criteria: guidelines of the EU-CARDIOPROTECTION COST Action. Basic Research in Cardiology. 2021; 116: P 52. 12. Heusch G. Critical Issues for the Translation of Cardioprotection. Circulation Research. 2017;120: P 1477–1486. 13. Hausenloy D.J.,Yellon D.M. Myocardial ischemia -reperfusionin jury: a neglected therapeutic target. Journal of Clinical Investiation 2013;123: P 92–100. 14. Kosiborod M, Birkeland KI, Cavender MA, Fu AZ, Wilding JP, Khunti K, et al. Rates of myocardial infarction and stroke in patients initiating treatment with SGLT2-inhibitors versus other glucose-lowering agents in real-world clinical practice: Results from the CVD- REALstudy.Diabetes, Obesity and Metabolism. 2018; 20: P 1983–1987. 15. Di Franco A, Cantini G, Tani A, Coppini R, Zecchi-Orlandini S, Raimondi L, et al. Sodium-dependent glucose transporters (SGLT) in human ischemic heart: a new potential pharmacological target. International Journal of Cardiology. 2017; 243: P 86–90. 16. Von Lewinski D, Benedikt M, Tripolt N, Wallner M, Sourij H, Kolesnik E. Can sodium glucose cotransporter 2 (SGLT-2) in inhibitors be beneficial in patients with acute myocardial infarctiontion? Cardiology Polska 2021; 79: P 503–509. 17. Asensio Lopez MDC, Lax A, Hernandez Vicente A, Saura Guillen E, Hernandez-Martinez A, Fernandez del Palacio MJ, et al. Empagliflozin improves post-infarction cardiac remodeling through GTP enzyme cyclohydrolase 1 and irrespective of diabetes status. Scientific Reports. 2020; 10: P 13553. 18. Baartscheer A, Schumacher CA, Wüst RCI, Fiolet JWT, Stienen GJM, Coronel R, et al. Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits. Diabetologia 2017; 60: P 568–573. 19. Uthman L, Baartscheer A, Bleijlevens B, Schumacher CA, Fi olet JWT, Koeman A, et al. Class effects of SGLT2 inhibitors in mouse cardiomyocytes and hearts: inhibition of Na+/H+ ex changer, lowering of cytosolic Na+ and vasodilation. Diabetologia. 2018; 61: P 722–726. 20. Koyani C N, Plastira I, Sourij H, Hallström S, Schmidt A, Rainer PP, et al. Empagliflozin protects heart from inflammation and energy depletion via AMPK activation. Pharmacological Research. 2020; 158: P 104870. 21. Santos- Gallego CG, Requena -Ibanez JA, San Antonio R, Ishikawa K, Watanabe S, Picatoste B, et al. Empagliflozin Ame liorates Adverse Left Ventricular Remodeling in Nondiabetic Heart Failure by Enhancing Myocardial Energetics. Journal of the American College of Cardiology. 2019; 73: P 1931–1944. 22. Zhou X ,Jin M, Liu L,Yu Z, Lu X, Zhang H. Trimethylamine N oxide and cardiovascular outcomes in patients with chronic heart failure after myocardial infarction. ESC Heart Failure. 2020; 7:188–193. 23. Andreadou I, Efentakis P, Balafas E, Togliatto G, Davos CH, Varela A, et al. Empagliflozin Limits Myocardial Infarction in Vivo and Cell Death in Vitro: Role of STAT3, Mitochondria, and Redox Aspects. Frontiers in Physiology. 2017; 8:1077. 24. Lahnwong S,Palee S, Apaijai N, Sriwichaiin S,Kerdphoo S, Jai Wongkam T,etal. Acute dapagliflozin administration implements cardioprotective effects in rats with cardiac ischemia/reperfusion injury. Cardiovascular Diabetology. 2020; 19:91. 25. Lee T, Chang N, Lin S. Dapagliflozin, a selective SGLT2 Inhibitor , attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts. Free Radical Biology and Medicine. 2017;104: 298–310. 26. The Lancet Diabetes & Endocrinology.Gettingtotheheartofthematter in type 2diabetes. The Lancet Diabetes & Endocrinology. 2015; 3:827. 27. Ceriello A, Genovese S, Mannucci E, Gronda E. Understanding EMPA-REG OUTCOME. The Lancet Diabetes & Endocrinology. 2015; 3: 929–930. 28. Gilbert RE, Connelly KA. Understanding EMPA-REG OUT COME. The Lancet Diabetes & Endocrinology. 2015; 3:930931. 29. Curtain JP, Docherty KF, Jhund PS, Petrie MC, Inzucchi SE, Køber L, et al. Effect of dapagliflozin on ventricular arrhythm mias , resuscitated cardiac arrest, or sudden death in DAPA-HF. European Heart Journal. 2021; 42: 3727–3738. 30. Clinical Trials.gov. A Study to Test the Effect of Empagliflozin in Patients Who Are in Hospital for Acute Heart Failure. Available at: https://clinicaltrials.gov/ct2/show/NCT04157751. Accessed: November 2021. 11 GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016; 388(10053):1459–544. 31. Voor AA, Angermann CE, Teerlink JR, et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med. (2022). DOI:10.1038/s41591-021-01659-1 32. Biegus J, Voors AA, Collins SP, Kosiborod MN, Teerlink JR, Angermann CE, et al. Impact of empagliflozin on decongestion in acute heart failure: the EMPULSE trial. Eur Heart J (2023) 44(1):41–50. doi: 10.1093/ eurheartj /ehac530 33. Bhatt DL, Szarek M, Steg PG, Cannon CP, Leiter LA, McGuire DK, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. (2021) 384(2):117–28. doi: 10.1056/nejmoa2030183 34.James S, Erlinge D, Storey RF, McGuire DK, de Belder M, Eriksson N, et al. Dapagliflozin in myocardial infarction without diabetes or heart failure. N Engl J Med. (2023) 3(2):EVIDoa2300286. doi: 10.1056/EVIDoa2300286 35. Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, et al. 2023 ESC guidelines for the management of acute coronary syndromes. Eur Heart J (2023) 44(38):3720–826. doi: 10.1093/ eurheartj /ehad191 36. Harrington J, Udell JA, Jones WS, Anker SD, Bhatt DL, Petrie MC, et al. Empagliflozin in patients post myocardial infarction rationale and design of the EMPACT-MI trial. Am Heart J (2022) 253(Mi):86–98. doi: 10.1016/j.ahj.2022.05.010 37. Rahhal A, Hamamyh T, Chapra A, Zaza KJ, Najim M, Hemadneh M, Faraj H, Kanjo W, Yasin A, Toba H, Mohammed W, Hamad MK, Al-Tikrety N, Baraa Habib M, Awaisu A, Mahfouz A, Alyafei S, Arabi AR, Patel A and Al-Hijji M (2024) Sodium– glucose cotransporter-2 inhibitors improve cardiovascular outcomes post-acute coronary syndrome complicated by acute heart failure. Front. Cardiovasc. Med. 11:1383669. https://doi.org/10.3389/fcvm.2024.1383669 38. Solomon SD, McMurray JJV, Claggett B et al. Dapagliflozin in heart failure with moderately reduced or preserved ejection fraction. N Engl J Med 2022; 387:1089 –98. https :// doi. org /10.1056/ NEJMoa 2206286 39. Herrington WG, Staplin N, Wanner C, et al. Empagliflozin in patients with chronic kidney disease. N Engl J Med 2023 ;388:117–27. https://doi.org/10.1056/NEJMoa2204233 40. Vaduganathan M, Docherty KF, Claggett BL, et al. SGLT -2 inhibitors in patients with heart failure: a comprehensive meta- analysis of five randomized controlled trials. Lancet 2022; 400: 757–67. https://doi.org/10.1016/S0140-6736(22)01429-5 41. SGLT 2 inhibitor meta-analysis investigators. Impact of diabetes on the effects of sodium-glucose cotransporter-2 inhibitors on renal outcomes: a collaborative meta-analysis of large placebo-controlled trials. Lancet 2022; 400:1788–801. https://doi.org/10.1016/S0140-6736(22)02074-8 . 42. SGLT2 Inhibitors in CKD and HFpEF: Two Large New Trials and Two New Meta-Analyses February 2023 Br J Cardiol 2023; 30: 7–9 doi : 10.5837 / bjc.2023.003 43. SGLT -2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomized controlled trials Muthiah Vaduganathan 1 , Kieran F. Docherty 2 Brian L. Claggett 1 , Pardeep S. Jund 2 , Rudolf A de Boer 3 , Adrian F. Hernandez 4 , Silvio E. Inzucchi 5 , Mikhail Nikolaevich Kosiborod 6 , Caroline SP Lam 7 Felipe Martinez 8 , Sanjeev J. Shah 9 Akshay With Desai 1 John J. W. Macmurray 2 Scott D. Solomon 10 PMID : 36041474 - DOI : 10.1016/ S 0140-6736(22)01429-5 .