SGLT-2 inhibitors in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus: A systematic review

Table 2 Randomised controlled trials

S. No	Ref.	Inclusion criteria	Age (yr)	Male gender	Intervention arm	Control arm	Follow-up duration	Primary outcome
1	Kuchay et al[11], 2018	Age > 20 yr, hepatic steatosis (MRI-PDFF > 6%), HbA1c > 7.0% to < 10.0%	Intervention arm: 50.7 (12.8)	Intervention arm: 16 (64%)	Standard treatment + Empagliflozin 10 mg daily (n = 25)	Standard treatment (n = 25)	20 wk	Change in liver fat content by MRI-PDFF
			Control arm: 49.1 (10.3)	Control arm: 17 (68%)
2	Ito et al[12], 2017	Age 20-75 yr, HbA1c 7.0–11.0%, BMI < 45 kg/m2, On diet and exercise therapy alone or with oral hypoglycaemic agents other than SGLT-2 inhibitors and thiazolidinediones and/or insulin, NAFLD, findings suggesting hepatic steatosis and hepatic dysfunction on clinical laboratory tests or on imaging studies (e.g., computed tomography or ultrasound)	Pioglitazone arm: 59.1 (9.8)	Pioglitazone arm: 18 (53%)	Ipragliflozin 50 mg daily (n = 32)	Pioglitazone 15-30 mg daily (n = 34)	24 wk	Change in L/S attenuation ratio
			Ipragliflozin arm: 57.3 (12.1)	Ipragliflozin arm: 14 (44%)
3	Shibuya et al[13], 2018	Fatty liver diagnosed on the basis of computed tomography or abdominal sonography, HbA1c 6.0%–10.0%, age 20–70 yr	Luseogliflozin arm: 51 (47-62)	Luseogliflozin arm: 10 (62.5%)	Luseogliflozin 2.5 mg daily (n = 16)	Metformin 1.5 g daily (n = 16)	24 wk	Change in L/S attenuation ratio
			Metformin arm: 60 (53-66)	Metformin arm: 8 (50%)
4	Eriksson et al[14], 2018	Age 40–75 yr, treated with a stable dose of metformin or sulfonylurea alone or in combination for at least 3 mo, MRI-PDFF > 5.5%, BMI 25–40 kg/m2	Dapagliflozin arm: 65 (6.5)	Dapagliflozin arm: 16 (76.2%)	Dapagliflozin 10 mg daily (n = 21) or Omega 3-carboxylic acid 4 g daily (n = 20) or Combination (n = 22)	Placebo (n = 21)	12 wk	Change in liver fat content by MRI-PDFF
			Omega 3-carboxylic acid arm: 66.2 (5.9)	Omega 3-carboxylic acid arm: 11 (55%)
			O + D arm: 65(5.4)	O + D arm: 15 (68.2%)
			Placebo arm: 65.6 (6.1)	Placebo arm: 17 (81%)

MRI-PDFF: Magnetic resonance imaging-derived proton density fat fraction; L/S: Liver/spleen; O + D: Omega 3-carboxylic acid + Dapagliflozin; SGLT-2: Sodium glucose cotransporter-2; NAFLD: Non-alcoholic fatty liver disease.