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Liraglutide may reduce liver enzyme levels in patients with type 2 diabetes

Patients with elevated liver enzymes were safely treated with liraglutide, although the treatment’s effect was reduced by its impact on weight and glycemic control, according to recent results.

Researchers performed a meta-analysis of data on 4,442 patients enrolled in six 26-week, phase 3 randomized controlled trials evaluating the impact of liraglutide on liver enzymes in patients with type 2 diabetes. Liraglutide was assigned to 2,734 patients in the cohort, while 524 received placebo and 1,184 received other diabetes treatments.

In all studies, patients initially received 0.6 mg intravenous liraglutide once a day, titrated to 1.2 mg daily after 7 days, with some studies increasing dosage to 1.8 mg after 7 additional days. One study (LEAD-2) randomly assigned patients to receive 0.6 mg, 1.2 mg or 1.8 mg once a day, along with metformin and 4 mg glimepiride or placebo per day. LEAD-2 also included a sub-study assessing the drug’s impact on hepatic steatosis.

Abnormal baseline ALT levels were present in 50.8% of patients. A 1.8 mg dose of liraglutide resulted in a significantly larger ALT reduction than that observed among patients receiving placebo (–8.20 IU/L vs. –5.01 IU/L; P=.003 for difference); no significant differences were observed between placebo and smaller doses of liraglutide. Investigators noted that adjusting for HbA1c (P=.63) and liraglutide’s weight reduction (P=.21) eliminated the statistical significance of the drug’s impact. Rates of adverse events were similar among patients with or without elevated ALT at baseline when treated with 1.2 mg or 1.8 mg liraglutide.

In the LEAD-2 sub-study, the 1.8 mg liraglutide dose trended toward improving steatosis relative to placebo, with a 0.10 improvement to liver-to-spleen attenuation ratio among treated patients compared with 0.0 among those receiving placebo (P=.07). Adjusting for changes to weight (P=.25) and HbA1c (P=.93) reduced this trend.

“[Twenty-six] weeks’ treatment with liraglutide 1.8 mg has an acceptable safety profile and significantly improves liver enzymes vs. placebo in patients with type 2 diabetes and asymptomatic liver injury,” the researchers wrote. “These effects appear to be mediated by the effect of liraglutide on weight loss and glycemic control. Our data support the rationale to prospectively investigate GLP-1 analogues in liver injury associated with type 2 diabetes and the metabolic syndrome.”

Disclosure: See the study for a full list of relevant disclosures.