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 (HbA(1)c), 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/m(2) (mean ± SD) with baseline IHL of 28.2% (16.5 to 43.1%) and HbA(1)c 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 ((1)H 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 HbA(1c) 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 HbA(1)c (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.

Figure 1. Upper: Relative changes in liver fat related to relative change in HbA₁c (ρ = 0.49; p = 0.01) (left) and absolute change in liver fat related to absolute change in HbA₁c (ρ = 0.38; p = 0.06) (right).

Lower: Relative changes in liver fat related to relative change in weight (ρ = 0.21; p = 0.31) (left) and absolute change in liver fat related to absolute change in weight (ρ = −0.04; p = 0.86) (right).

Figure 2. Correlation between changes in liver fat (%) and: Upper: change in total abdominal fat (litres).

Middle: change in abdominal subcutaneous fat (litres). Lower: change in intra-abdominal visceral fat (litres).

Figure 3. Upper Change in liver fat according to weight loss of <5% and >5% and according to relative reduction in HbA1c above or below median (median absolute reduction in HbA1c = 1.3%).

Lower: Change in liver fat according to pre-treatment liver fat percentage (left) and individual plots to demonstrate changes in liver fat ranked by pre-treatment liver fat percentage (right).