Non-alcoholic fatty liver disease and diabetes: From physiopathological interplay to diagnosis and treatment

Table 3 Current data on pharmacological treatments of non-alcoholic fatty liver disease

Ref.	Sample size	Type 2 diabetes	Type of intervention/ drug	Study design/duration	Liver enzymes	Imaging	Histology
Parker et al[116]	355		Omega-3 PUFA: 0.8-13.7 g/d	Systematic review and meta-analysis (9 studies) median duration of treatment: 6 mo	Significant efficacy of PUFA on ALT and AST levels	Significant efficacy of PUFA on liver fat (US, 1H-MRS)
Lindor et al[119]	166		UDCA: 13-15 mg/kg per day	Randomized placebo-controlled study (24 mo)	No significant changes in ALT, AST and GGT levels with UDCA		No significant changes in NASH or fibrosis with UDCA
Leuschner et al[120]	185		UDCA: 23-28 mg/kg per day	Randomized placebo-controlled study (18 mo)	No significant changes in ALT and AST, ↓ GGT levels with UDCA		No significant changes in NASH or fibrosis with UDCA
Uygun et al[121]	36	0%	Metformin: 1.7 g/d	Randomized placebo-controlled study (6 mo)	Significant ↓ in ALT and AST levels with metformin	Significant efficacy of metformin on liver fat (US)	No significant ↓ in inflammatory activity or fibrosis with metformin
Haukeland et al[122]	48	27%	Metformin: 2.5-3 g/d	Randomized placebo-controlled study (6 mo)	No significant changes in ALT, AST levels with metformin	No significant ↓ on liver fat (CT) with metformin	No significant changes in NASH with metformin
Shields et al[123]	19	0%	Metformin: 500 mg-1 g/d	Randomized placebo-controlled trial (12 mo)	No significant changes in ALT and AST levels with metformin		No significant changes in NASH or fibrosis with metformin
Lutchman et al[126]	18	0%	Pioglitazone: 30 mg/d	Prospective open study (12 mo)	ALT levels normalized in 72%	Hepatic fat content was ↓ by MR imaging	significant ↓ in necroinflammation and fibrosis with pioglitazone
Belfort et al[127]	55	48%	Pioglitazone: 45 mg/d	Randomized placebo-controlled study (6 mo)	Significant efficacy of pioglitazone on ALT and AST levels	Significant efficacy of pioglitazone on liver fat (1H-MRS)	Significant ↓ in necroinflammation but not in fibrosis with pioglitazone
Aithal et al[128]	74	0%	Pioglitazone: 30 mg/d	Randomized placebo-controlled trial (12 mo)	Significant ↓ in ALT and GGT levels		Significant ↓ in inflammatory activity and fibrosis with pioglitazone
Sanyal et al[129]	247	0%	Vitamin E: 800 UI/dPioglitazone: 30 mg/d	Randomized placebo-controlled trial (24 mo)	Significant ↓ in ALT, AST and GGT levels with both treatments		Significant ↓ of NASH with vitamin E. No changes in fibrosis with either treatment

↓: Decrease; ↑: Increase. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gammaglutamyl transferase; AP: Alkaline phosphatase; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; PUFA: Polyunsaturated fatty acids; UDCA: Ursodeoxycholic acid; US: Ultrasonography; MR: Magnetic resonance;

¹H-MRS: Proton magnetic resonance spectroscopy; CT: Computed tomography.