Effects of treatment with SGLT-2 inhibitors on arginine-related cardiovascular and renal biomarkers

Table 1 Plasma concentrations of biomarkers after empagliflozin/dapagliflozin treatment

	At baseline	After placebo		After verum			Reference values in healthy populations (2.5th–97.5th centile) [32]
	At baseline		p-value [adj. p-value] vs. baseline (n)		p-value [adj. p-value] vs. baseline (n)	p-value [adj. p-value] vs. placebo (n)
Empagliflozin
Homoarginine	1.667 ± 0.589	1.631 ± 0.593	0.484 [0.660] (71)	1.376 ± 0.481	< 0.001 [0.027] (71)	< 0.001 [< 0.001] (71)	1.4–2.6
Arginine	70.44 ± 16.82	71.63 ± 14.25	0.539 [0.705] (71)	68.27 ± 19.32	0.292 [0.453] (71)	0.122 [0.261] (71)	41–114
ADMA	0.434 ± 0.062	0.429 ± 0.064	0.476 [0.660] (71)	0.436 ± 0.056	0.768 [0.863] (71)	0.338 [0.507] (71)	0.41–0.96
SDMA	0.371 ± 0.072	0.355 ± 0.062	0.008 [0.028] (71)	0.396 ± 0.076	< 0.001 [< 0.001] (71)	< 0.001 [0.002] (71)	0.27–0.67
Creatinine	65.35 ± 13.04	65.57 ± 12.69	0.808 [0.866] (71)	67.11 ± 14.18	0.055 [0.146] (71)	0.050 [0.141] (71)	n.a
Dapagliflozin
Homoarginine	1.593 ± 0.555	1.581 ± 0.589	0.899 [0.963] (57)	1.375 ± 0.465	< 0.001 [0.007] (59)	< 0.001 [0.007] (57)	1.4–2.6
Arginine	72.60 ± 20.23	70.79 ± 19.16	0.635 [0.774] (57)	71.70 ± 19.17	0.739 [0.831] (59)	0.980 [0.984] (57)	41–114
ADMA	0.448 ± 0.057	0.423 ± 0.072	0.003 [0.034] (57)	0.429 ± 0.066	0.021 [0.090] (59)	0.365 [0.604] (57)	0.41–0.96
SDMA	0.364 ± 0.068	0.351 ± 0.073	0.061 [0.153] (57)	0.377 ± 0.076	0.026 [0.090] (59)	< 0.001 [0.007] (57)	0.27–0.67
Creatinine	66.13 ± 13.94	65.35 ± 15.47	0.706 [0.831] (57)	68.25 ± 14.85	0.040 [0.120] (59)	0.053 [0.140] (57)	n.a

Data are given in µM as mean ± SD, n.a.: not applicable; p-values calculated by two-sided paired t-tests, adj. p-values computed based on the procedure of Benjamini and Hochberg; p-values refer to the absolute changes in biomarker concentration

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