Dapagliflozin, Empagliflozin ve Eksenatid Kullanan Tip 2 Diyabetli Hastalarda Kardiyovasküler Olay Oranlarının Retrospektif Olarak Değerlendirilmesi

Öz

Tip 2 diyabet hastalarında kardiyovasküler hastalıklar diyabeti olmayanlara göre daha yüksektir. SGLT-2 inhibitörlerinin (empagliflozin, dapagliflozin vb.) ve GLP-1 analoglarının (exenatid vb.) kardiyak etkilerine ilişkin olumlu sonuçlar veren geniş çaplı çalışmalar mevcuttur. Bu çalışmayla empagliflozin, dapagliflozin veya eksenatid kullanan hastalarda kardiyovasküler sonuçları değerlendirmek ve karşılaştırmak amaçlanmıştır. Kontrol grubu olarak kardiyak açıdan nötr olduğu bilinen DPP-4 inhibitörü (linagliptin) kullanan hastalar seçilmiştir. Bu çalışma her tedavi grubundan (linagliptin, eksenatid, dapagliflozin, empagliflozin) en az on iki aydır tedavi gören 100 hasta olmak üzere toplam 400 hasta ile gerçekleştirilmiştir. Miyokard enfarktüsü (MI), serebrovasküler olay (SVO), kardiyak nedenlere bağlı ölüm, majör kardiyovasküler olay (MACE: MI, SVO ve kardiyak ölüm), kalp yetmezliği nedeniyle hastaneye yatış, kararsız angina/akut koroner sendrom (AKS), periferik arter hastalığı ve tüm nedenlere bağlı ölümler değerlendirilmiştir. Tüm kardiyovasküler patolojilerin toplam oranları incelendiğinde linagliptin grubunda %10, eksenatid grubunda %6, dapagliflozin grubunda %4 ve empagliflozin grubunda %6 olarak tespit edilmiştir. Kardiyak hastalık öyküsü olmayan hastalar karşılaştırıldığında eksenatid, dapagliflozin ve empagliflozin grubunda toplam kardiyovasküler patoloji oranlarının linagliptin grubuna göre istatistiksel olarak anlamlı derecede azaldığı saptanmıştır. Kardiyak öyküsü olan hastalarda ise dapagliflozin ve empagliflozin grubunda angina/AKS tablosunun anlamlı derecede azaldığı ortaya konmuştur. Bu sonuçlar diyabet hastalarının kardiyak patolojilerden birincil korunmasında eksenatid, dapagliflozin ve empagliflozin moleküllerinin faydalı olduğunu göstermektedir. Dapagliflozin ve empagliflozin molekülleirinin hastaların kardiyovasküler patolojilerden sekonder korunmasında da tekili olabileceğini düşündürmektedir.

Anahtar Kelimeler

• : Linagliptin
• Eksenatid
• Dapagliflozin
• Empagliflozin
• SGLT-2 inhibitörleri
• Kardiyovasküler Olay

Retrospective Evaluation of The Rate of Cardiovascular Events in Type 2 Diabetic Patients Using Dapagliflozin, Empagliflozin and Exenatide

Öz

Cardiovascular diseases are more common in patients with type 2 diabetes than in those without diabetes. Large-scale studies have shown positive results regarding the cardiac effects of SGLT-2 inhibitors (empagliflozin, dapagliflozin, etc.) and GLP-1 analogs (exenatide, etc.). This study aimed to evaluate and compare cardiovascular outcomes in patients using empagliflozin, dapagliflozin, or exenatide. Patients using a DPP-4 inhibitor (linagliptin), known as cardiac neutral, were selected as the control group. This study was conducted with 400 patients, 100 of whom received treatment for at least twelve months from each treatment group (linagliptin, exenatide, dapagliflozin, and empagliflozin). Myocardial infarction (MI), cerebrovascular accident (CVA), death due to cardiac causes, major cardiovascular event (MACE: MI, CVA, and cardiac death), hospitalization due to heart failure, unstable angina/acute coronary syndrome (ACS), peripheral artery disease and all-cause deaths were evaluated. When the total rates of all cardiovascular pathologies were examined, it was determined that they were 10% in the linagliptin group, 6% in the exenatide group, 4% in the dapagliflozin group and 6% in the empagliflozin group. When patients without a history of cardiac disease were compared, it was determined that the total cardiovascular pathology rates in the exenatide, dapagliflozin, and empagliflozin groups were statistically significantly reduced compared to the linagliptin group. In patients with a cardiac history, it was revealed that angina/ACS was significantly reduced in the dapagliflozin and empagliflozin groups. These results show that exenatide, dapagliflozin, and empagliflozin molecules are helpful in the primary prevention of cardiac pathologies in our diabetic patients. Dapagliflozin and empagliflozin molecules may also be unique in the secondary protection of patients from cardiovascular pathologies.

Anahtar Kelimeler

• Linagliptin
• Exenatide
• Dapagliflozin
• Empagliflozin
• SGLT-2 inhibitors
• Cardiovascular event

Kaynakça

1. 1.Cho NH, Shaw JE, Karuranga S, et al. IDF Diabetes Atlas:Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271-281.
2. 2.Booth GL, Kapral MK, Fung K, Tu J V. Relation between age and cardiovascular disease in men and women with diabetes compared with non-diabetic people: a population-based retrospective cohort study. Lancet. 2006;368(9529):29-36.
3. 3.Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl JMed. 2016;375(4):311-322.
4. 4.Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors forprimary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019;393(10166):31-39.
5. 5.Zinman B, Wanner C, Lachin JM, et al. Empagliflozin,Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-2128.
6. 6.Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med.2019;380(4):347-357.
7. 7.Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 DiabetesMellitus. N Engl J Med. 2013;369(14):1317-1326.
8. 8.Green JB, Bethel MA, Armstrong PW, et al. Effect ofSitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2015;373(3):232-242.

9. 9.Rosenstock J, Perkovic V, Johansen OE, et al. Effect ofLinagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular andRenal Risk. JAMA. 2019;321(1):69.
10. 10.Rosenstock J, Kahn SE, Johansen OE, et al. Effect ofLinagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes. JAMA.2019;322(12):1155.
11. 11.Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome. N Engl JMed. 2015;373(23):2247-2257.
12. 12.Holman RR, Bethel MA, Mentz RJ, et al. Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2Diabetes. N Engl J Med. 2017;377(13):1228-1239.
13. 13.Nauck MA, Kahle M, Baranov O, Deacon CF, Holst JJ.Addition of a dipeptidyl peptidase-4 inhibitor, sitagliptin, to ongoing therapy with the glucagon-like peptide-1 receptor agonist liraglutide: A randomized controlled trial in patients with type 2 diabetes. Diabetes, Obes Metab. 2017;19(2):200-207.
14. 14.Clar C, Gill JA, Court R, Waugh N. Systematic review ofSGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes. BMJ Open. 2012;2(5):e001007.
15. 15.Ueda P, Svanström H, Melbye M, et al. Sodium glucosecotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study. BMJ. 2018;363:k4365.
16. 16.Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): adouble-blind, randomised placebo-controlled trial. Lancet. 2019;394(10193):121-130.
17. 17.Ural D. Systematic Review, Meta-analysis and Meta-regression of Epidemiological Studies for Cardiovascular Risk Factors conducted in Turkey: Obesity Data. Turk Kardiyol Dern Arsivi-Archives Turkish Soc Cardiol. 2018;46(7):577-590.
18. 18.Packham DK, Alves TP, Dwyer JP, et al. Relative Incidence ofESRD Versus Cardiovascular Mortality in Proteinuric Type 2Diabetes and Nephropathy: Results From the DIAMETRIC(Diabetes Mellitus Treatment for Renal Insufficiency Consortium) Database. Am J Kidney Dis. 2012;59(1):75-83.
19. 19.Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019;380(24):2295-2306.
20. 20.Abrahami D, Douros A, Yin H, et al. Dipeptidyl peptidase-4 inhibitors and incidence of inflammatory bowel disease amongpatients with type 2 diabetes: population based cohort study.BMJ. 2018;360:k872.
21. 21.Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl JMed. 2017;377(7):644-657.
22. 22.Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019;380(4):347-357.
23. 23.Zheng XD, Qu Q, Jiang XY, Wang ZY, Tang C, Sun JY.Effects of Dapagliflozin on Cardiovascular Events, Death, and Safety Outcomes in Patients with Heart Failure: A Meta-Analysis. American Journal of Cardiovascular Drugs. 2021;21(3):321-330.
24. 24.Kato ET, Silverman MG, Mosenzon O, et al. Effect ofDapagliflozin on Heart Failure and Mortality in Type 2Diabetes Mellitus. Circulation. 2019;139(22):2528-2536.
25. 25.McMurray JJV, DeMets DL, Inzucchi SE, et al. A trial to evaluate the effect of the sodium–glucose co‐transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA‐HF). Eur J Heart Fail. 2019;21(5):665-675.
26. 26.Rafla mariam, Abdelraheem M, Hareedy M, ELSAUGHIER S.Potential Cardio-protective Role of Dapagliflozin in Post Myocardial Infarction Patients. Aswan University Medical Journal. 2023;0(0):0
27. 27.Shimizu W, Kubota Y, Hoshika Y, et al. Effects ofempagliflozin versus placebo on cardiac sympathetic activity in acute myocardial infarction patients with type 2 diabetesmellitus: the EMBODY trial. Cardiovasc Diabetol. 2020;19(1):148.
28. 28.Pellicori P, Ofstad AP, Fitchett D, et al. Early benefits ofempagliflozin in patients with or without heart failure: findings from EMPA‐REG OUTCOME. ESC Heart Fail. 2020;7(6):3401-3407.
29. 29.Wanner C, Lachin JM, Inzucchi SE, et al. Empagliflozin and Clinical Outcomes in Patients With Type 2 Diabetes Mellitus, Established Cardiovascular Disease, and Chronic Kidney Disease. Circulation. 2018;137(2):119-129.
30. 30.Verma S, Mazer CD, Yan AT, et al. Effect of Empagliflozin on Left Ventricular Mass in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease. Circulation. 2019;140(21):1693-1702.