Combination Therapy of RAS Inhibition and SGLT2 Inhibitors Decreases Levels of Endotrophin in Persons with Type 2 Diabetes
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Combination Therapy of RAS Inhibition and SGLT2 Inhibitors Decreases Levels of Endotrophin in Persons with Type 2 Diabetes. / Møller, Alexandra Louise; Thöni, Stefanie; Keller, Felix; Sharifli, Samir; Rasmussen, Daniel Guldager Kring; Genovese, Federica; Karsdal, Morten Asser; Mayer, Gert.
In: Biomedicines, Vol. 11, No. 11, 3084, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Combination Therapy of RAS Inhibition and SGLT2 Inhibitors Decreases Levels of Endotrophin in Persons with Type 2 Diabetes
AU - Møller, Alexandra Louise
AU - Thöni, Stefanie
AU - Keller, Felix
AU - Sharifli, Samir
AU - Rasmussen, Daniel Guldager Kring
AU - Genovese, Federica
AU - Karsdal, Morten Asser
AU - Mayer, Gert
N1 - Publisher Copyright: © 2023 by the authors.
PY - 2023
Y1 - 2023
N2 - We investigated for the first time the effect of combination therapy of renin–angiotensin system inhibition (RASi) and sodium–glucose co-transporter-2 inhibitors (SGLT2is) on endotrophin (ETP), a pro-fibrotic signaling molecule reflecting collagen type VI formation, measured in the plasma of persons with type 2 diabetes (T2D). ETP was measured using the PRO-C6 ELISA in 294 individuals from the “Drug combinations for rewriting trajectories of renal pathologies in type 2 diabetes” (DC-ren) project. In the DC-ren study, kidney disease progression was defined as a >10% decline in the estimated glomerular filtration rate (eGFR) to an eGFR < 60 mL/min/1.73 m2. Among the investigated circulating markers, ETP was the most significant predictor of future eGFR. Combination therapy of RASi and SGLT2is led to a significant reduction in ETP levels compared to RASi monotherapy (p for slope difference = 0.002). Higher levels of baseline plasma ETP were associated with a significantly increased risk of kidney disease progression (p = 0.007). In conclusion, plasma ETP identified individuals at higher risk of kidney disease progression. The observed decreased levels of plasma ETP with combination therapy of RASi and SGLT2is in persons with T2D may reflect a reduced risk of kidney disease progression following treatment with SGLT2is.
AB - We investigated for the first time the effect of combination therapy of renin–angiotensin system inhibition (RASi) and sodium–glucose co-transporter-2 inhibitors (SGLT2is) on endotrophin (ETP), a pro-fibrotic signaling molecule reflecting collagen type VI formation, measured in the plasma of persons with type 2 diabetes (T2D). ETP was measured using the PRO-C6 ELISA in 294 individuals from the “Drug combinations for rewriting trajectories of renal pathologies in type 2 diabetes” (DC-ren) project. In the DC-ren study, kidney disease progression was defined as a >10% decline in the estimated glomerular filtration rate (eGFR) to an eGFR < 60 mL/min/1.73 m2. Among the investigated circulating markers, ETP was the most significant predictor of future eGFR. Combination therapy of RASi and SGLT2is led to a significant reduction in ETP levels compared to RASi monotherapy (p for slope difference = 0.002). Higher levels of baseline plasma ETP were associated with a significantly increased risk of kidney disease progression (p = 0.007). In conclusion, plasma ETP identified individuals at higher risk of kidney disease progression. The observed decreased levels of plasma ETP with combination therapy of RASi and SGLT2is in persons with T2D may reflect a reduced risk of kidney disease progression following treatment with SGLT2is.
KW - biomarker
KW - collagen
KW - diabetic kidney disease
KW - endotrophin
KW - extracellular matrix
KW - fibrosis
U2 - 10.3390/biomedicines11113084
DO - 10.3390/biomedicines11113084
M3 - Journal article
C2 - 38002084
AN - SCOPUS:85178369686
VL - 11
JO - Biomedicines
JF - Biomedicines
SN - 2227-9059
IS - 11
M1 - 3084
ER -
ID: 377447966