Impact of sodium glucose cotransporter-2 inhibitors on liver steatosis/fibrosis/inflammation and redox balance in non-alcoholic fatty liver disease

Table 1 Baseline characteristics of patients observed in the study (n = 52) and included in groups treated with the sodium-glucose co-transporter-2 inhibitors or other glucose lowering drugs

Variable	SGLT2-I (n = 26)	OTHER (n = 26)	P value
Age (yr)	60.6 ± 6.78	63.4 ± 10.4	0.246
Sex (male/female)	15/11	15/11	1.000
BMI (kg/m2)	34.8 ± 7.7	34.5 ± 5.9	0.875
No comorbidities, n (%)	2 (7.7)	2 (7.7)	1.000
Dyslipidemia, n (%)	13 (50.0)	15 (57.7)	0.578
Hypertension, n (%)	10 (38.5)	15 (57.7)	0.165
Chronic heart failure, n (%)	8 (30.8)	3 (11.5)	0.089
Chronic kidney disease, n (%)	9 (34.6)	4 (15.4)	0.109
AST (U/L)	48.5 ± 26.6	54.7 ± 13.3	0.293
ALT (U/L)	49.6 ± 39.2	65.0 ± 18.7	0.077
Gamma-GT (U/L)	151.3 ± 87.2	179.2 ± 56.9	0.178
Tryglycerides (mg/dL)	140.2 ± 45.9	133.5 ± 33.2	0.549
Fasting glucose (mg/dL)	150.1 ± 45.9	159.7 ± 49.8	0.473
HbA1c (%)	9.24 ± 3.01	8.73 ± 2.31	0.496
Creatininemia (mg/dL)	1.01 ± 0.44	0.88 ± 0.32	0.229
eGFR (mL/min/1.73 m2)	61.4 ± 38.9	73.2 ± 24.6	0.197
Albuminemia (g/dL)	3.91 ± 0.44	4.08 ± 0.47	0.184
Platelets (n, × 103/mm3)	175.7 ± 113.1	179.7 ± 76.7	0.882

BMI: Body mass index; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; Gamma-GT: Gamma-glutamyl transpeptidase; HbA1c: Hemoglobin A1c; eGFR: Epidermal growth factor receptor; SGLT2-I: Sodium-glucose co-transporter-2 inhibitor; OTHER: Other glucose lowering drug.

Table 2 Non-invasive markers of hepatic fibrosis in patients observed in the study (n = 52) and included in groups treated with the sodium-glucose co-transporter-2 inhibitors or other glucose lowering drugs at baseline (T0) and after 6 mo of therapy (T1)

		T0	T1	P value
NAFLD fibrosis score (F3/4), n (%)	SGLT2-I (n = 26)	9 (34.6)	4 (15.4)	0.042
	OTHER (n = 26)	7 (26.9)	7 (26.9)
FIB-4 (F3/4), n (%)	SGLT2-I (n = 26)	11 (42.3)	6 (23.1)	0.036
	OTHER (n = 26)	7 (26.9)	7 (26.9)
AST/ALT ≥ 0.8, n (%)	SGLT2-I (n = 26)	15 (57.7)	6 (23.1)	0.001
	OTHER (n = 26)	10 (38.5)	11 (42.3)

NAFLD: Non-alcoholic fatty liver disease; FIB-4: Fibrosis-4; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; SGLT2-I: Sodium-glucose co-transporter-2 inhibitor; OTHER: Other glucose lowering drug.

Table 3 Circulating interleukin levels in patients enrolled in the study and included in groups treated with the sodium-glucose co-transporter-2 inhibitors or other glucose lowering drugs before (T0) and after 1 wk of treatment (T1)

Variable	SGLT2-I (n = 26)		OTHER (n = 26)		Fisher’s test (1, 100)
	T0	T1	T0	T1	Time	Treatment	Interaction
IL-1α (pg/mL)	1.35 ± 1.64	1.58 ± 1.30	1.44 ± 1.88	1.59 ± 1.56	0.373	0.026	0.016
IL-1β (pg/mL)	9.90 ± 2.39	7.31 ± 3.51e	8.84 ± 2.54	9.15 ± 2.42	4.455a	0.521	7.207b
IL-2 (U/mL)	≤ 0.5	≤ 0.5	≤ 0.5	≤ 0.5	-	-	-
IL-4 (pg/mL)	5.39 ± 4.20	8.54 ± 3.51d	4.89 ± 3.54	5.94 ± 3.66	8.207b	4.471a	2.052
IL-6 (pg/mL)	9.41 ± 4.21	6.92 ± 1.98	11.4 ± 5.41	13.7 ± 9.01h	0.007	15.4c	4.516a
IL-8 (pg/mL)	428 ± 216	409 ± 271	412 ± 296	449 ± 204	0.338	0.060	0.327
IL-10 (pg/mL)	1.33 ± 1.02	2.31 ± 1.12e	1.29 ± 1.06	1.32 ± 1.04g	5.894a	6.130a	5.214a
TNF (pg/mL)	6.82 ± 3.02	4.61 ± 2.01d	7.94 ± 3.14	7.81 ± 3.56g	3.989a	13.59c	3.151
VEGF (pg/mL)	262 ± 162	142 ± 109d	244 ± 201	268 ± 147f	2.393	3.029	5.384a
IFN-γ (pg/mL)	0.53 ± 0.23	0.57 ± 0.57	0.50 ± 0.39	0.61 ± 0.44	0.809	0.004	0.176
MCP-1 (pg/mL)	411 ± 168	291 ± 156	389 ± 154	414 ± 184f	2.131	2.408	4.964a
EGF (pg/mL)	25.7 ± 13.7	22.2 ± 12.1	24.9 ± 20.1	23.6 ± 18.6	0.553	0.009	0.116

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

^dP < 0.05 vs sodium-glucose co-transporter-2 inhibitor T0.

^eP < 0.01 vs sodium-glucose co-transporter-2 inhibitor T0.

^fP < 0.05 vs sodium-glucose co-transporter-2 inhibitor T1.

^gP < 0.01 vs sodium-glucose co-transporter-2 inhibitor T1.

^hP < 0.001 vs sodium-glucose co-transporter-2 inhibitor T1.

Data are expressed as mean ± SD. Statistical differences were assessed by two-way analysis of variance. VEGF: Vascular endothelial growth factor; MCP-1: Monocyte chemoattractant protein-1; EGF: Epidermal growth factor; SGLT2-I: Sodium-glucose co-transporter-2 inhibitor; OTHER: Other glucose lowering drug; IL: Interleukin; TNF: Tumor necrosis factor; IFN: Interferon.