Improved Glycaemia Correlates with Liver Fat Reduction in Obese, Type 2 Diabetes, Patients Given Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are effective for obese patients with type 2 diabetes mellitus (T2DM) because they concomitantly target obesity and dysglycaemia. Considering the high prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with T2DM, we determined the impact of 6 months’ GLP-1 RA therapy on intrahepatic lipid (IHL) in obese, T2DM patients with hepatic steatosis, and evaluated the inter-relationship between changes in IHL with those in glycosylated haemoglobin (HbA1c), body weight, and volume of abdominal visceral and subcutaneous adipose tissue (VAT and SAT). We prospectively studied 25 (12 male) patients, age 50±10 years, BMI 38.4±5.6 kg/m2 (mean ± SD) with baseline IHL of 28.2% (16.5 to 43.1%) and HbA1c of 9.6% (7.9 to 10.7%) (median and interquartile range). Patients treated with metformin and sulphonylureas/DPP-IV inhibitors were given 6 months GLP-1 RA (exenatide, n = 19; liraglutide, n = 6). IHL was quantified by liver proton magnetic resonance spectroscopy (1H MRS) and VAT and SAT by whole body magnetic resonance imaging (MRI). Treatment was associated with mean weight loss of 5.0 kg (95% CI 3.5,6.5 kg), mean HbA1c reduction of 1·6% (17 mmol/mol) (0·8,2·4%) and a 42% relative reduction in IHL (−59.3, −16.5%). The relative reduction in IHL correlated with that in HbA1c (ρ = 0.49; p = 0.01) but was not significantly correlated with that in total body weight, VAT or SAT. The greatest IHL reduction occurred in individuals with highest pre-treatment levels. Mechanistic studies are needed to determine potential direct effects of GLP-1 RA on human liver lipid metabolism.

Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus

“…Finally, in another study, improved glucose control correlated with liver fat reduction in obese T2DM patients given GLP-1 receptor agonists exenatide or liraglutide for 6 months [60] . There is growing evidence that incretin-based therapies have beneficial effects on hepatocytes; however, further study analysis are needed to assess the long-term effect of incretin-based therapies on NAFLD [19] .…”

“…Exenatide has been shown to improve glucose control in patients with T2DM and concomitant NAFLD [59][60][61] or NASH [62] . A recently published animal study suggested that SIRT 1 , a NAD+-dependent protein deacetylase that is considered as a crucial regulator in hepatic lipid homeostasis, mediates the effect of exenatide on ameliorating hepatic steatosis [63] .…”

Metabolically healthy and unhealthy obesity: differential effects on myocardial function according to metabolic syndrome, rather than obesity

“…Liver lipid was measured non-invasively using proton magnetic resonance spectroscopy ( 1 H-MRS) as previously described [31][32][33] . NAFLD was defined as intrahepatocellular lipid content (IHCL) > 5.5% measured by 1 H-MRS. Three voxels of interest were identified in the liver avoiding ducts and vasculature and the mean value taken after data were processed independently.…”

Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders

“…As part of studies powered to detect changes in glycaemic control in patients with type 2 diabetes and NAFLD, they caused a reduction in intrahepatic lipid as measured by MRS in addition to reductions in body weight and improved glycaemic control (98). In a separate analysis of type 2 diabetic patients treated with Liraglutide, there was a dose-dependent but non-significant improvement in hepatic steatosis, measured by liver-spleen attenuation ration as well as improvements in abnormal liver function tests (99).…”