TİP 2 DİYABET TEDAVİSİNDE SGLT-2 İNHİBİTÖRLERİNİN ETKİNLİĞİ: TEK MERKEZ DENEYİMİ

Abstract

Amaç: Sodyum-glukoz taşıyıcı-2 (SGLT-2) inhibitörleri, insülin sekresyonunu etkilemeden renal glukoz reabsorpsiyonunu azaltarak kan glukozunu düşürür. Çalışmamızın amacı, Tip 2 diabetes mellituslu (T2DM) hastalarda SGLT-2 inhibitör tedavisinin glisemik kontrol üzerindeki etkisini ve ilaçların olası üstünlüklerini klinik parametreler ve laboratuvar bulguları ile karşılaştırarak değerlendirmektir. Gereç ve Yöntem: SGLT-2 inhibitörü tedavisi [empagliflozin (EMPA) (n=146) veya dapagliflozin (DAPA) (n=73)/10 mg] alan 219 T2DM hastalarının verileri geriye dönük olarak kaydedildi. Demografik özellikler, detaylı tıbbi öykü, komorbiditeler, komplikasyonlar, vücut ağırlığı ve kan basıncı takibi, laboratuvar bulguları (başlangıçta, 3. ve 12. aylarda) incelendi. Bulgular: Bu çalışmamızda SGLT-2 tedavisinden sonra ortalama HbA1c ve açlık plazma glukoz değerleri başlangıç değerlerine göre anlamlı oranda azaldı. Ortalama vücut ağırlığı ve ürik asit değerleri tedavinin 3. ayında anlamlı oranda azaldı. Benzer şekilde karaciğer fonksiyon testleri değerlerinde de tedavi sonrası iyileşmeler görüldü. Sonuç: SGLT-2 inhibitörlerinin T2DM hastalarında glisemik kontrol ve karaciğer fonksiyonu üzerindeki olumlu etkileri açıkça gösterilmiştir. Ayrıca klinik parametreler, laboratuvar bulguları ve ilaç güvenliği açısından EMPA ve DAPA arasında önemli bir fark saptanmamıştır.

Keywords

• Tip 2 diabetes mellitüs
• sodyum glukoz kotransporterlar
• empagliflozin
• dapagliflozin

EFFICACY OF SGLT-2 INHIBITORS IN THE TREATMENT OF TYPE 2 DIABETES: SINGLE CENTRE EXPERIENCE

Abstract

Objective: Sodium-glucose transporter-2 (SGLT-2) inhibitors lower blood glucose levels by reducing renal glucose reabsorption without affecting insulin secretion. The aim of our study was to evaluate the effect of SGLT-2 inhibitor treatment on glycemic control and the possible superiority of the drugs by comparing clinical parameters and laboratory findings in Type 2 diabetes mellitus (T2DM) patients. Material and Methods: Two hundred and nineteen T2DM patients who received SGLT-2 inhibitor therapy [empagliflozin (EMPA) (n=146) or dapagliflozin (DAPA) (n=73)/10 mg] were enrolled retrospectively. The patients’ demographic characteristics, detailed medical history, comorbidities, physical examination findings, complications, weight and systolic-diastolic blood pressure follow-up, laboratory findings (at baseline, 3rd, and 12th month), and overall follow-up outcomes were evaluated. Result: The mean values of HbA1c and fasting blood glucose (FBG) decreased significantly compared with the baseline values after the treatment. The mean body weight and uric acid values were significantly reduced in the 3rd month of the treatment. Similarly, the values of the liver function tests decreased substantially after treatment. Conclusion: The beneficial effects of SGLT-2 inhibitors on glycemic control and liver functions in patients with T2DM have been demonstrated. In addition, there was no major difference in terms of clinical parameters, laboratory findings, and drug safety in patients between EMPA and DAPA.

Keywords

• Type 2 diabetes mellitus
• sodium-glucose cotransporters
• empagliflozin
• dapagliflozin

References

1. Khan MA, Hashim MJ, King JK, Govender RD, Mustafa H. Epidemiology of type 2 diabetes-global burden of disease and forecasted trends. J Epidemiol Glob Health 2020;10(1):107-11. [CrossRef] google scholar
2. Zheng Y, Ley SH, Hu FB. Global etiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol 2018;14(2):88-98. [CrossRef] google scholar
3. Chaudhury A, Duvoor C, Reddy Dendi VS, Kraleti S, Chada A, Ravilla R, et al. Clinical review of antidiabetic drugs: implications for type 2 diabetes mellitus management. Front Endocrinol (Lausanne) 2017;24:8:6. [CrossRef] google scholar
4. Thrasher J. Pharmacologic management of type 2 diabetes mellitus: available therapies. The Am J Cardiol 2017;120(1): S4-16. [CrossRef] google scholar
5. Fitchett D. A safety update on sodium glucose co-transporter 2 inhibitors. Diabetes Obes Metab 2019;21(Suppl 2):34-42. [CrossRef] google scholar
6. Tang H, Li D, Zhang J, Li Y, Wang T, Zhai S, et al. Sodium-glucose co-transporter-2 inhibitors and risk of adverse renal outcomes among patients with type 2 diabetes: a network and cumulative meta-analysis of randomized controlled trials. Diabetes Obes Metab 2017;19(8):1106-15. [CrossRef] google scholar
7. Matthaei S, Bowering K, Rohwedder K, Grohl A, Parikh S. Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial. Diabetes Care 2015;38(3):365-72. [CrossRef] google scholar
8. Lopaschuk GD, Verma S. Mechanisms of cardiovascular benefits of sodium glucose co- transporter 2 (SGLT2) inhibitors: a state-of-the-art review. JACC Basic Transl Sci 2020;5(6):632-44. [CrossRef] google scholar

9. Donnan JR, Grandy CA, Chibrikov E, Marra CA, Aubrey-Bassler K, Johnston K, et al. Comparative safety of the sodium glucose co- transporter 2 (SGLT2) inhibitors: a systematic review and meta-analysis. BMJ open 2019;9(1):e022577. [CrossRef] google scholar
10. Rossing P, Caramori ML, Chan JCN, Heerspink HJL, Hurst C, Khunti K, et al. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int 2022;102(5):S1-127. [CrossRef] google scholar
11. Devi R, Mali G, Chakraborty I, Unnikrishnan MK, Abdulsalim S. Efficacy and safety of empagliflozin in type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. Postgrad Med 2017;129(3):382-92. [CrossRef] google scholar
12. Brown E, Rajeev SP, Cuthbertson DJ, Wilding JP. A review of the mechanism of action, metabolic profile and hemodynamic effects of sodium-glucose co-transporter-2 inhibitors. Diabetes Obes Metab 2019;21:9-18. [CrossRef] google scholar
13. Berhan A, Barker A. Sodium glucose co-transport 2 inhibitors in the treatment of type 2 diabetes mellitus: a meta-analysis of randomized double-blind controlled trials. BMC Endocr Disord 2013;13:58. [CrossRef] google scholar
14. Toyama T, Neuen BL, Jun M, Ohkuma T, Neal B, Jardine JM, et al. Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: a systematic review and meta-analysis. Diabetes Obes Metab 2019;21(5):1237-50. [CrossRef] google scholar
15. Liakos A, Karagiannis T, Athanasiadou E, Sarigianni M, Mainou M, Papatheudorou K, et al. Efficacy and safety of empagliflozin for type 2 diabetes: a systematic review and metaanalysis. Diabetes Obes Metab 2014;16(10):984-93. [CrossRef] google scholar
16. Bailey CJ. Uric acid and the cardio-renal effects of SGLT2 inhibitors. Diabetes Obes Metab 2019;21(6):1291-8. [CrossRef] google scholar
17. Zhao Y, Xu L, Tian D, Xia P, Zheng H, Wang L, et al. Effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid level: a meta-analysis of randomized controlled trials. Diabetes Obes Metab 2018;20(2):458-62. [CrossRef] google scholar
18. Lee PC, Gu Y, Yeung MY, Fong CH, Woo YC, Chow WS, et al. Dapagliflozin and empagliflozin ameliorate hepatic dysfunction among chinese subjects with diabetes in part through glycemic improvement: a single-center, retrospective, observational study. Diabetes Ther 2018;9(1):285-95. [CrossRef] google scholar
19. Gunhan HG, Imre E, Erel P, Ustay O. Empagliflozin is more effective in reducing microalbuminuria and alt levels compared with dapagliflozin: real life experience. Acta Endocrinologica (Bucharest) 2020;16(1):59. [CrossRef] google scholar
20. Cherney D, Lund SS, Perkins BA, Groop PH, Cooper ME, Kaspers S, et al. The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes. Diabetologia 2016;59(9):1860-70. [CrossRef] google scholar
21. Liu XY, Zhang N, Chen R, Zhao JG, Yu P. Efficacy and safety of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes: a meta-analysis of randomized controlled trials for 1 to 2 years. J Diabetes Complications 2015;29(8):1295-303. [CrossRef] google scholar
22. Xu L, Li Y, Lang J, Xia P, Zhao X, Wang L, et al. Effects of sodium-glucose co- transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes: a systematic review and meta-analysis. PeerJ 2017;5:e3405. [CrossRef] google scholar
23. glucose co-transporter-2 inhibitor dapagliflozin on estimated plasma volume in patients with type 2 diabetes. Diabetes Obes Metab 2019;21(12):2667-73. [CrossRef] google scholar
24. Marathias KP, Lambadiari VA, Markakis KP, Vlahakos VD, Bacharaki D, Raptis AE, et al. Competing Effects of Renin Angiotensin System Blockade and Sodium-Glucose Cotransporter-2 Inhibitors on Erythropoietin Secretion in Diabetes. Am J Nephrol 2020;51(5):349-56. [CrossRef] google scholar
25. Aberle J, Menzen M, Schmid SM, Terkamp C, Jaeckel E, Rohwedder K, et al. Dapagliflozin effects on haematocrit, red blood cell count and reticulocytes in insulin-treated patients with type 2 diabetes. Scientific Reports 2020;10(1):1-8. [CrossRef] google scholar
26. Dekkers CC, Petrykiv S, Laverman GD, Cherney DZ, Gansevoort RT, Heerspink HJL, et al. Effects of the SGLT-2 inhibitor dapagliflozin on glomerular and tubular injury markers. Diabetes Obes Metab 2018;20(8):1988-93. [CrossRef] google scholar
27. Filippas-Ntekouan S, Filippatos TD, Elisaf MS. SGLT2 inhibitors: are they safe? Postgrad Med 2018;130(1):72-82. [CrossRef] google scholar
28. Ku EJ, Lee DH, Jeon HJ, Oh TK. Empagliflozin versus dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin, glimepiride and dipeptidyl peptide 4 inhibitors: A 52-week prospective observational study. Diabetes Res Clin Pract 2019;151:65-73. [CrossRef] google scholar