BACKGROUND AND AIM: Effective medicines have not been introduced for insulin resistance-related fatty liver. 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-naïve patients with impaired glucose metabolism and fatty liver were compared. METHODS:Fifty-two patients with fasting glucose 100-240 mg/dL or glycosylated hemoglobin (HbA1c) ≥ 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 end-point was a change from baseline ALT level. Secondary end-points were changes in fasting glucose, HbA1c, aspartate aminotransferase levels, mitochondrial DNA (mtDNA) copy number in the peripheral blood, and urinary output of 8-hydroxy-2'-deoxyguanosine, 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 HbA1c 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-hydroxy-2'-deoxyguanosine level and increased mtDNA copy number significantly compared with metformin alone (both P < 0.05). No severe adverse events were observed. CONCLUSION: 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).
RCT Entities:
BACKGROUND AND AIM: Effective medicines have not been introduced for insulin resistance-related fatty liver. 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-naïve patients with impaired glucose metabolism and fatty liver were compared. METHODS: Fifty-two patients with fasting glucose 100-240 mg/dL or glycosylated hemoglobin (HbA1c) ≥ 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 end-point was a change from baseline ALT level. Secondary end-points were changes in fasting glucose, HbA1c, aspartate aminotransferase levels, mitochondrial DNA (mtDNA) copy number in the peripheral blood, and urinary output of 8-hydroxy-2'-deoxyguanosine, 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 HbA1c 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-hydroxy-2'-deoxyguanosine level and increased mtDNA copy number significantly compared with metformin alone (both P < 0.05). No severe adverse events were observed. CONCLUSION: 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).
Authors: Han Ah Lee; Young Chang; Pil Soo Sung; Eileen L Yoon; Hye Won Lee; Jeong-Ju Yoo; Young-Sun Lee; Jihyun An; Do Seon Song; Young Youn Cho; Seung Up Kim; Yoon Jun Kim Journal: Clin Mol Hepatol Date: 2022-07-01