.: DERLEME
Sodyum-Glukoz Ko-Transporter 2 İnhibitörlerinin Renal ve Kardiyovasküler Sonuçlar Üzerine Etkileri: Sistematik Derleme
Effects of Sodium-Glucose Co-Transporter 2 Inhibitors on Renal and Cardiovascular Outcomes: Systematic Review
Turkiye Klinikleri J Med Sci. 2021;41(3):346-52
doi: 10.5336/medsci.2021-84266
Makale Dili: TR
Tam Metin
ÖZET
Tip 2 diabetes mellitus (T2DM), dünya çapında en yaygın kronik hastalıklar arasındadır ve bu süreçte kardiyovasküler (KV) komplikasyonların önlenmesi önemli bir tedavi hedefidir. Sodyum-glukoz ko-transporter-2 (SGLT2) inhibitörleri, glukozun büyük oranda geri emiliminin sağlandığı böbrek proksimal tübüllerinde glukoz reabsorbsiyonunu engelleyerek antidiyabetik etki gösterirler. Üriner glukoz kaybındaki artışa karşın, metabolik adaptasyon olarak keton cisimciklerin enerji üretiminde artmış kullanımı ve vücut yağ yüzdesinde azalma meydana gelir. SGLT2 inhibitörleri; intraglomerüler basıncı ve hiperfiltrasyonu azaltır ve böylece filtrasyon bariyeri üzerindeki fiziksel stres, albüminüri ve tübüler reabsorpsiyon için gerekli oksijen talebi azaltılmış olur. Bu avantaj sayesinde; daha az glukotoksisite ve uzun vadede tübüler işlevi koruyan kortikal oksijenizasyonda optimal iyileşme sağlanır. SGLT2 inhibitörleri ayrıca sistemik hipoksiyi benzeri bir mekanizma ile eritropoezi uyarabilir. Öte yandan; aterosklerotik kardiyovasküler hastalığı ve T2DM tanılı hastalarda, farklı SGLT2 inhibitörleri ile yapılan çalışmalarda KV ölüm ilişkili heterojen sonuçlar olması nedeniyle ileri çalışmalara olan ihtiyaç ortadadır. Son yıllardaki geniş çaplı randomize klinik çalışmalar, SGLT2 inhibitörlerinin T2DM olsun olmasın tüm kalp yetersizliği (KY) olgularında klinik yararlar sağlayabileceği ve kronik böbrek hasarı progresyonunu yavaşlatabileceği düşüncesini ortaya koymuştur. Mevcut bilimsel veriler ışığında; SGLT2 inhibitörleri, kardiyorenal avantajları sayesinde ilgili güncel kılavuzlarda önemli bir yer edinmektedir. Bu derlemede, SGLT2 inhibitörlerinin KY ve kronik böbrek hastalığı tedavisindeki güncel rolü gözden geçirilmiştir.
Anahtar Kelimeler: Diabetes mellitus; kalp yetersizliği; kronik böbrek hastalığı; sodyum-glukoz ko-transporter 2 inhibitörleri
Tip 2 diabetes mellitus (T2DM), dünya çapında en yaygın kronik hastalıklar arasındadır ve bu süreçte kardiyovasküler (KV) komplikasyonların önlenmesi önemli bir tedavi hedefidir. Sodyum-glukoz ko-transporter-2 (SGLT2) inhibitörleri, glukozun büyük oranda geri emiliminin sağlandığı böbrek proksimal tübüllerinde glukoz reabsorbsiyonunu engelleyerek antidiyabetik etki gösterirler. Üriner glukoz kaybındaki artışa karşın, metabolik adaptasyon olarak keton cisimciklerin enerji üretiminde artmış kullanımı ve vücut yağ yüzdesinde azalma meydana gelir. SGLT2 inhibitörleri; intraglomerüler basıncı ve hiperfiltrasyonu azaltır ve böylece filtrasyon bariyeri üzerindeki fiziksel stres, albüminüri ve tübüler reabsorpsiyon için gerekli oksijen talebi azaltılmış olur. Bu avantaj sayesinde; daha az glukotoksisite ve uzun vadede tübüler işlevi koruyan kortikal oksijenizasyonda optimal iyileşme sağlanır. SGLT2 inhibitörleri ayrıca sistemik hipoksiyi benzeri bir mekanizma ile eritropoezi uyarabilir. Öte yandan; aterosklerotik kardiyovasküler hastalığı ve T2DM tanılı hastalarda, farklı SGLT2 inhibitörleri ile yapılan çalışmalarda KV ölüm ilişkili heterojen sonuçlar olması nedeniyle ileri çalışmalara olan ihtiyaç ortadadır. Son yıllardaki geniş çaplı randomize klinik çalışmalar, SGLT2 inhibitörlerinin T2DM olsun olmasın tüm kalp yetersizliği (KY) olgularında klinik yararlar sağlayabileceği ve kronik böbrek hasarı progresyonunu yavaşlatabileceği düşüncesini ortaya koymuştur. Mevcut bilimsel veriler ışığında; SGLT2 inhibitörleri, kardiyorenal avantajları sayesinde ilgili güncel kılavuzlarda önemli bir yer edinmektedir. Bu derlemede, SGLT2 inhibitörlerinin KY ve kronik böbrek hastalığı tedavisindeki güncel rolü gözden geçirilmiştir.
Anahtar Kelimeler: Diabetes mellitus; kalp yetersizliği; kronik böbrek hastalığı; sodyum-glukoz ko-transporter 2 inhibitörleri
ABSTRACT
Type 2 diabetes mellitus (T2DM) is among the most common chronic diseases worldwide and prevention of cardiovascular (CV) complications is an important treatment goal in this process. sodium-glucose co-transporter-2 (SGLT2) inhibitors show antidiabetic effects by preventing glucose reabsorption in the proximal tubules of the kidney where glucose is largely reabsorbed. Metabolic adaptations to induced urinary glucose loss include reduced fat mass and more ketone bodies as additional fuel. SGLT2 inhibitors lower glomerular capillary hypertension and hyperfiltration, thereby reducing the physical stress on the filtration barrier, albuminuria, and the oxygen demand for tubular reabsorption. This improves cortical oxygenation, which, together with lesser tubular gluco-toxicity, may preserve tubular function and glomerular filtration rate in the long term. SGLT2 inhibitors may mimic systemic hypoxia and stimulate erythropoiesis, which improves organ oxygen delivery. The heterogeneity of the associations with outcomes of different SGLT2 inhibitors on CV death among patients with T2D and atherosclerotic cardiovascular disease requires further study. Large-scale randomized clinical trials in recent years have suggested that SGLT2 inhibitors can provide clinical benefits and slow the progression of chronic kidney disease in all cases of heart failure (HF), with or without T2DM. In the light of the present results; SGLT2 inhibitors occupy an important place in relevant current guidelines due to their cardiorenal advantages. We aimed to reviews the current role of SGLT2 inhibitors in the treatment of HF and chronic kidney disease.
Keywords: Diabetes mellitus; heart failure; chronic kidney disease; sodium-glucose co-transporter 2 inhibitors
Type 2 diabetes mellitus (T2DM) is among the most common chronic diseases worldwide and prevention of cardiovascular (CV) complications is an important treatment goal in this process. sodium-glucose co-transporter-2 (SGLT2) inhibitors show antidiabetic effects by preventing glucose reabsorption in the proximal tubules of the kidney where glucose is largely reabsorbed. Metabolic adaptations to induced urinary glucose loss include reduced fat mass and more ketone bodies as additional fuel. SGLT2 inhibitors lower glomerular capillary hypertension and hyperfiltration, thereby reducing the physical stress on the filtration barrier, albuminuria, and the oxygen demand for tubular reabsorption. This improves cortical oxygenation, which, together with lesser tubular gluco-toxicity, may preserve tubular function and glomerular filtration rate in the long term. SGLT2 inhibitors may mimic systemic hypoxia and stimulate erythropoiesis, which improves organ oxygen delivery. The heterogeneity of the associations with outcomes of different SGLT2 inhibitors on CV death among patients with T2D and atherosclerotic cardiovascular disease requires further study. Large-scale randomized clinical trials in recent years have suggested that SGLT2 inhibitors can provide clinical benefits and slow the progression of chronic kidney disease in all cases of heart failure (HF), with or without T2DM. In the light of the present results; SGLT2 inhibitors occupy an important place in relevant current guidelines due to their cardiorenal advantages. We aimed to reviews the current role of SGLT2 inhibitors in the treatment of HF and chronic kidney disease.
Keywords: Diabetes mellitus; heart failure; chronic kidney disease; sodium-glucose co-transporter 2 inhibitors
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