Liraglutide Decreases Liver Fat Content and Serum Fibroblast Growth Factor 21 Levels in Newly Diagnosed Overweight Patients with Type 2 Diabetes and Nonalcoholic Fatty Liver Disease

Abstract

Purposes. In this study, we aimed to verify plasma fibroblast growth factor 21 (FGF21) elevation in newly diagnosed overweight patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) and to evaluate the effectiveness of liraglutide on reducing liver fat content and serum (FGF21) levels in those patients. Methods. A 12-week, single-center, prospective study was conducted. Twenty newly diagnosed overweight patients with T2DM and NAFLD were recruited. Twenty healthy age, sex, and body mass index (BMI) matched subjects were enrolled as the control group. Enzyme-linked immunosorbent assay was used to measure serum FGF21 levels. Liver fat content was determined using the 3.0 T whole-body MRI scanner. Results. Those newly diagnosed overweight patients with T2DM and NAFLD had a BMI of 27.6 ± 0.5 kg/m2. They had higher levels of FGF21 ( 159.6 ± 35.7 vs. 124.1 ± 42.9 pg/ml, P < 0.001 ) and increased liver fat content ( 19.3 ± 9.4 vs. 4.5 ± 0.6 %, P < 0.001 ) compared to the controls. Liraglutide treatment for 12 weeks induced a significant 4.9 kg weight loss (95% confidence interval (CI): -6.1, -3.7, P < 0.001 ), which was equivalent to a relative reduction of 6.8% (95% CI: 5.3%, 8.3%, P < 0.001 ). FGF21 levels decreased after the 12-week liraglutide treatment ( 159.6 ± 35.7 vs. 124.2 ± 27.8 pg/ml, P = 0.006 ). There was a positive correlation between relative changes of liver fat content and relative change of FGF21 ( r = 0.645 , P = 0.002 ). FGF21 levels significantly decreased in patients who had a significant decrease in liver fat content (≥29%) (95% CI: -262.8, -55.1, P = 0.006 ); however, there was no significant change in the patients without a significant decrease in liver fat content (<29%) (95% CI: -60.0, 54.1, P = 0.899 ). Conclusions. Liraglutide treatment reduced both liver fat content and FGF21 levels in newly diagnosed overweight patients with T2DM and NAFLD. FGF21 may be a potential biomarker for evaluating the effects of liraglutide treatment on hepatic fat and glucose metabolism.

Fibroblast Growth Factor-21 as a Potential Therapeutic Target of Nonalcoholic Fatty Liver Disease

“… 77 Another uncontrolled study, exploring the effect of liraglutide, an anti-diabetic medication with beneficial impact on hepatic steatosis and inflammation, 78 on FGF-21, supported that circulating FGF-21 decreased only in patients with significant decrease in hepatic steatosis. 79 Notably, there was positive association between change in FGF-21 and HFC in this study. However, whether FGF-21 partly mediates the beneficial effect of liraglutide on HFC needs studies of different design.…”

“… Change in circulating FGF-21 was positively associated with changes in HFC and FIB-4. Li (2021) 79 Prospective, uncontrolled Overweight patients with newly diagnosed T2DM and MRI-defined NAFLD (20) No control group prospectively Liraglutide 0.6–1.8 mg/d 12 weeks No Effect of liraglutide on circulating FGF-21 and HFC. Reduced circulating FGF21 only in patients with significant decrease in HFC (≥29%).…”

Targeting FGF21 in cardiovascular and metabolic diseases: from mechanism to medicine

“…Serum FGF21 levels can reflect the improvement of NAFLD in patients who received weight loss intervention in a prospective observational pilot study 182 . FGF21 levels can also be used to evaluate the effects of liraglutide, a drug that can reduce liver fat content, in overweight patients with NAFLD 183 .…”

Interplay between metabolic dysfunction-associated fatty liver disease and chronic kidney disease: Epidemiology, pathophysiologic mechanisms, and treatment considerations

“…Other inflammatory and oxidative pathways in the liver could be inhibited by GLP1-RAs, such as the receptor for advanced glycation end products/nicotinamide-adenine dinucleotide phosphate oxidase 2, limiting liver injury and fibrosis in mice on a high-fat diet[ 97 ]. Concerning human studies, patients with MAFLD treated with GLP1-RAs have exhibited a significant reduction in liver fat, which may be positively correlated to fibroblast growth factor 21[ 70 ]. The use of GLP1-RAs also resulted in a significant reduction of MAFLD prevalence (defined based on hepatic steatosis index > 36) during a 24-mo follow-up[ 71 ].…”