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Clinical hepatology
OP03 Effects of two years of liraglutide treatment on fatty liver disease in patients with type 2 diabetes: analysis of the Liraglutide Effect and Action in Diabetes-2 extension trial
  1. M Armstrong1,
  2. A Falahati1,
  3. D D Houlihan2,
  4. B Elbrand1,
  5. W E Schmidt1,
  6. S Gough1,
  7. P N Newsome1
  1. 1Centre for Liver Research, University of Birmingham, UK
  2. 2Oxford Centre for Diabetes, Churchill Hospital, UK

Abstract

Introduction Currently there are no established treatment options for fatty liver disease. Glucagon-like peptide 1 (GLP-1) analogues have been shown to reduce hepatic steatosis and markers of liver inflammation in rodents.

Aim To determine the efficacy of 2 years treatment with 1.8 mg liraglutide, a once-daily human GLP-1 analogue, on fatty liver disease and body composition in patients with poorly controlled type 2 diabetes (T2D).

Method Analysis was performed on the “Liraglutide Effect and Action in Diabetes-2” (LEAD-2) study cohort. LEAD-2 was a 26-week, double blind phase III trial with a 1.5-year open-label extension. Patients were randomised (2:2:2:2:1) to liraglutide 1.8, 1.2 or 0.6 mg/day, glimepiride 4 mg/day or placebo, all in combination with metformin 1.5–2 g/day. DEXA (n=160) and computerised tomography (CT) (n=154) sub-studies were performed to measure body fat composition and hepatic steatosis (defined by a liver-to-spleen attenuation ratio <1), respectively.

Repeated measure and ANCOVA analysis was performed using last observation carried forward on the intention-to-treat population to estimate change from baseline. Values expressed as mean (SD).

Results 529/1091 patients (58% male; 87% white; age 56.7 years (9.5); body mass index 31 kg/m2 (4.7); HbA1c 8.4% (0.9); male alanine aminotransferase (ALT) 32.0 IU/L (17.9); female ALT 27.3 IU/L (14.9)) completed 2 years treatment. Of the subjects enrolled in the sub-study 75% had the metabolic syndrome (ATP III classification) and 65.7 % (90/137) had hepatic steatosis on CT at baseline.

Patients with elevated ALT levels (53%) at baseline (males >30, female >19 IU/L) had a significant reduction of ALT with liraglutide (−8.53 from baseline 40.9 IU/l, p<0.0001). This was a significant improvement vs glimepiride (p<0.05). 37% of patients normalised their ALT with liraglutide in comparison to 21% on glimepiride.

Liver-to-spleen attenuation ratio significantly increased with liraglutide (+0.10, p<0.05) indicating reduced hepatic steatosis. Reductions in trunk fat tissue mass, trunk lean tissue mass and % total body fat with liraglutide were significantly different vs increases with glimepiride (−3.0 kg, −1.3 kg, −2.05%, respectively; p<0.05). Greater improvements were seen in liver-to-spleen attenuation ratio (+0.05), trunk fat mass (−1.6 kg) and % total body fat (−0.63%) with liraglutide vs placebo.

Conclusion Two years treatment with liraglutide significantly improves liver enzymes and hepatic steatosis in patients with T2D and associated fatty liver disease. Significant improvements in % body fat, in particular central adiposity support the role of liraglutide in reducing hepatic steatosis and cardiovascular morbidity.

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