SGLT2 İnhibitörleri ile Tedavi Edilen Tip 2 Diyabet Hastalarında FIB-4 Seyri ve Karaciğer Fibrozis Yanıtının Belirleyicileri: Eşleştirilmiş Örneklemle 12 Aylık Bir Çalışma
Abstract
Özet
Giriş: Sodyum-glukoz kotransportör 2 (SGLT2) inhibitörlerinin metabolik parametreler üzerinde olumlu etkileri gösterilmiştir; ancak Fibrosis-4 (FIB-4) skoru gibi karaciğer fibrozis indeksleri üzerindeki etkileri henüz yeterince araştırılmamıştır. Empagliflozin ve dapagliflozinin hepatik ve metabolik belirteçler üzerindeki karşılaştırmalı etkinliğinin anlaşılması, tip 2 diyabet mellitus (T2DM) hastalarında tedavi stratejilerine yön verebilir.
Yöntemler: Bu çalışmaya empagliflozin veya dapagliflozin tedavisine başlanan T2DM hastaları dahil edildi ve 12 ay boyunca takip edildi. Başlangıçta ve 12. ayda; kilo, HbA1c, lipid profili, ALT, AST ve FIB-4 skoru dahil olmak üzere klinik ve laboratuvar parametreler değerlendirildi. FIB-4 skorunda ≥%20 azalma gösterenler “yanıtlayan”, göstermeyenler “yanıtlamayan” olarak kabul edilerek eğilim skoru eşleştirmesi (propensity score matching) uygulandı. FIB-4 iyileşmesini öngören belirteçleri değerlendirmek amacıyla ROC (receiver operating characteristic) analizi yapıldı.
Bulgular: Toplam 200 hasta analiz edildi. Hem empagliflozin hem de dapagliflozin gruplarında BKİ, açlık kan şekeri, HbA1c ve FIB-4 skorlarında anlamlı düşüşler gözlendi (tümünde p < 0.001). Gruplar arası karşılaştırmalarda ΔBKİ, ΔHbA1c, ΔAST ve ΔFIB-4 açısından istatistiksel olarak anlamlı fark saptanmadı. Yanıtlayan hastalarda başlangıç FIB-4 skoru anlamlı şekilde daha düşüktü (1.48±0.52 vs. 1.80±0.42; p = 0.0445). ROC analizinde, FIB-4 yanıtının en güçlü belirleyicisi olarak ΔAST ≥7 U/L bulundu (EAA = 0.875, duyarlılık = %83, özgüllük = %83).
Sonuç: Her iki SGLT2 inhibitörü de T2DM hastalarında metabolik ve hepatik parametrelerde anlamlı iyileşmeler sağlamıştır. AST düzeyindeki azalmanın büyüklüğü, FIB-4 skorundaki iyileşmenin güçlü bir belirleyicisi olarak öne çıkmakta ve tedaviye karaciğerin verdiği yanıtın izlenmesinde potansiyel bir rol taşıdığı görülmektedir.
Keywords
SGLT2 inhibitörleri empagliflozin dapagliflozin FIB-4 skoru karaciğer fibrozisi diabetes mellitus
Thanks
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References
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FIB-4 Trajectories and Predictors of Fibrosis Response in Type 2 Diabetes Treated with SGLT2 Inhibitors: A Propensity-Matched 12-Month Study
Abstract
Abstract
Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated favorable effects on metabolic parameters, yet their impact on liver fibrosis indices such as the Fibrosis-4 (FIB-4) score remains underexplored. Understanding the comparative efficacy of empagliflozin and dapagliflozin in modulating hepatic and metabolic markers could guide therapeutic strategies in patients with type 2 diabetes mellitus (T2DM).
Methods: This study included patients with T2DM who were initiated on empagliflozin or dapagliflozin and followed for 12 months. Clinical and laboratory parameters were assessed at baseline and 12 months, including weight, HbA1c, lipid profile, ALT, AST, and FIB-4 score. Propensity score matching was employed to identify responders (≥20% reduction in FIB-4) and non-responders. Receiver operating characteristic (ROC) analysis was performed to evaluate predictive markers for FIB-4 improvement.
Results: A total of 200 patients were analyzed. Both empagliflozin and dapagliflozin groups demonstrated significant reductions in BMI, FBG, HbA1c, and FIB-4 scores (p < 0.001 for all). Between-group comparisons revealed no statistically significant differences in ΔBMI, ΔHbA1c, ΔAST, or ΔFIB-4. Among responders, the baseline FIB-4 score was significantly lower (1.48±0.52 vs. 1.80±0.42; p = 0.0445). ROC analysis identified ΔAST ≥7 U/L as the strongest predictor of FIB-4 response (AUC = 0.875, sensitivity = 83%, specificity = 83%).
Conclusion: Both SGLT2 inhibitors significantly improved metabolic and hepatic parameters in patients with T2DM. The magnitude of AST reduction emerged as a robust predictor of FIB-4 improvement, underscoring its potential role in monitoring hepatic response to treatment.
References
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- 2. Ma X, Liu Z, Ilyas I, et al. GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential. Int J Biol Sci. 2021;17(8):2050–68. doi:10.7150/ijbs.59965
- 3. Jiang Y, Wang L, Zhu X, et al. Advances in management of metabolic dysfunction-associated steatotic liver disease: from mechanisms to therapeutics. Lipids Health Dis. 2024;23(1):95. doi:10.1186/s12944-024-02092-2
- 4. Younossi ZM, Golabi P, de Avila L, et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta-analysis. J Hepatol. 2019;71(4):793–801. doi:10.1016/j.jhep.2019.06.021
- 5. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328–57. doi:10.1002/hep.29367
- 6. Hiraoka A, Kumada T, Kudo M, et al. Albumin–Bilirubin (ALBI) grade as part of the evidence-based clinical practice guideline for HCC of the Japan Society of Hepatology: a comparison with the liver damage and Child–Pugh classifications. Liver Cancer. 2017;6(3):204–15. doi:10.1159/000475705
- 7. Mantovani A, Petracca G, Csermely A, et al. Sodium-glucose cotransporter-2 inhibitors for treatment of nonalcoholic fatty liver disease: a meta-analysis of randomized controlled trials. Metabolites. 2020;11(1):22. doi:10.3390/metabo11010022
- 8. Arai T, Atsukawa M, Tsubota A, et al. Antifibrotic effect and long-term outcome of SGLT2 inhibitors in patients with NAFLD complicated by diabetes mellitus. Hepatol Commun. 2022;6(11):3073–82. doi:10.1002/hep4.2069
- 9. Shinozaki S, Tahara T, Lefor AK, Ogura M. Long-term empagliflozin therapy improves levels of hepatic fibrosis marker in patients with NAFLD complicated by type 2 diabetes mellitus. J Med Invest. 2020;67(3–4):280–4. doi:10.2152/jmi.67.280
- 10. Liu H, Hao YM, Jiang S, et al. Evaluation of MASLD fibrosis, FIB-4 and APRI score in MASLD combined with T2DM and MACCEs receiving SGLT2 inhibitors treatment. Int J Gen Med. 2024;17:2613–25. doi:10.2147/IJGM.S460200
- 11. Kuchay MS, Krishan S, Mishra SK, et al. Effect of empagliflozin on liver fat in patients with type 2 diabetes and NAFLD: a randomized controlled trial (E-LIFT trial). Diabetes Care. 2018;41(8):1801–8. doi:10.2337/dc18-0165
- 12. Kahl S, Gancheva S, Strassburger K, et al. Empagliflozin effectively lowers liver fat content in well-controlled type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Diabetes Care. 2020;43(2):298–305. doi:10.2337/dc19-0690
- 13. Lai LL, Vethakkan SR, Nik Mustapha NR, et al. Empagliflozin for the treatment of nonalcoholic steatohepatitis in patients with type 2 diabetes mellitus. Dig Dis Sci. 2020;65(2):623–31. doi:10.1007/s10620-019-05859-1
- 14. Shibuya T, Fushimi N, Kawai M, et al. Luseogliflozin improves liver fat deposition compared to metformin in T2DM patients with NAFLD: a prospective randomized controlled pilot study. Diabetes Obes Metab. 2018;20(2):438–42. doi:10.1111/dom.13100
- 15. Takahashi H, Kessoku T, Kawanaka M, et al. Ipragliflozin improves the hepatic outcomes of patients with diabetes with NAFLD. Hepatol Commun. 2022;6(1):120–32. doi:10.1002/hep4.1816
- 16. Ohashi N, Ishigaki S, Isobe S, et al. Empagliflozin alleviates steatohepatitis and fibrosis in a mouse model of NASH. Hepatol Res. 2021;51(3):313–22. doi:10.1111/hepr.13567
- 17. Tahara A, Matsuyama-Yokono A, Nakano K, et al. Effects of dapagliflozin on steatohepatitis and hepatic fibrosis in experimental models. Sci Rep. 2021;11(1):1125. doi:10.1038/s41598-021-81176-w
Details
| Primary Language | English |
|---|---|
| Subjects | Internal Diseases |
| Journal Section | Articles |
| Authors | |
| Publication Date | June 30, 2025 |
| Submission Date | May 11, 2025 |
| Acceptance Date | June 9, 2025 |
| Published in Issue | Year 2025 Volume: 8 Issue: 2 |
