Authors and Disclosures
Eun Shil Hong, Eun Ky Kim, Seon Mee Kang, Ah Reum Khang, Sung Hee Choi, Kyong Soo Park, Hak Chul Jang, and Soo Lim
Article Type: Original Article – Hepatology (Clinical)
Received Date : September 21, 2013
Accepted Date : January 13, 2014
ABSTRACT
BACKGROUND / AIM
Effective medicines have not been introduced for insulin resistance related fatty liver. We compared the efficacy and safety of treatment between a combination of metformin and carnitine-orotate complex and metformin alone in a 12-week, double-blind, randomized, placebo-controlled study on drug-naive patients with impaired glucose metabolism and fatty liver.
METHODS
Fifty-two patients with fasting glucose 100-240 mg/dL or HbAlc >6.0% and alanine aminotransferase (ALT) 40-250 IU/L were randomized to receive metformin (250 mg t.i.d.), or metformin (250 mg t.i.d.) and carnitine-orotate complex (300 mg t.i.d.) for 12 weeks (n=26 per group). The primary endpoint was a change from baseline ALT level. Secondary endpoints were changes in fasting glucose, HbAlc, aspartate aminotransferase (AST) levels, mitochondrial DNA (mtDNA) copy number in the peripheral blood, and urinary output of 8- hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative stress.
RESULTS
The combined treatment reduced ALT level significantly more than metformin alone (—51.5 + 33.2 IU/L vs. -16.7 + 31.3 IU/L, P=0.001). The HbAlIc levels also decreased significantly in both groups but there was no significant difference between them (—0.9 + 1.0%, vs. —0.7 + 0.9%). Treatment with the complex decreased the urinary 8-OHdG level and increased mtDNA copy number significantly compared with metformin alone (both P<0.05). No severe adverse events were observed.
CONCLUSIONS
A 12-week treatment with metformin and _ carnitine-orotate complex significantly improved liver function enzyme levels. This was associated with changes in oxidative stress and mtDNA copy number compared with metformin alone in patients with impaired glucose metabolism and fatty liver (clinical trial number: KCT0000193).