Effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in drug-naive subjects with type 2 diabetes

Abstract

Ectopic accumulation of lipids in nonadipose tissues plays a primary role in the pathogenesis of type 2 diabetes mellitus (T2DM). This study was to examine the effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in T2DM. Thirty-three drug-naive T2DM patients (age 52.7 ± 1.7 years, HbA1c 8.7 ± 0.2 %, body mass index 24.5 ± 0.5 kg/m(2)) were randomized into exenatide, insulin, or pioglitazone for 6 months. Intrahepatic fat (IHF), visceral fat (VF), and subcutaneous fat (SF) were measured using proton nuclear magnetic resonance spectroscopy. Plasma tumor necrosis factor α (TNFα) and adiponectin were assayed by ELISA. HbA1c declined significantly in all three groups. Body weight, waist, and serum triglycerides decreased with exenatide. After interventions, IHF significantly reduced with three treatments (exenatide Δ = -68 %, insulin Δ = -58 %, pioglitazone Δ = -49 %). Exenatide reduced VF (Δ = -36 %) and SF (Δ = -13 %), and pioglitazone decreased VF (Δ = -30 %) with no impact on SF, whereas insulin had no impact on VF or SF. Levels of TNFα (exenatide/insulin/pioglitazone) decreased, and levels of adiponectin (exenatide/pioglitazone) increased. Analysis showed that ΔIHF correlated with ΔHbA1c and Δweight. Besides, ΔIHF correlated with Δtriglycerides and ΔTNFα, but the correlations fell short of significance after BMI adjustment. By linear regression analysis, ΔHbA1c alone explained 41.5 % of the variance of ΔIHF, and ΔHbA1c + Δweight explained 57.6 % of the variance. Liver fat content can be significantly reduced irrespective of using exenatide, insulin, and pioglitazone. Early glycaemic control plays an important role in slowing progression of fatty liver in T2DM.

Different effects of basal insulin peglispro and insulin glargine on liver enzymes and liver fat content in patients with type 1 and type 2 diabetes

“…LFC decreases in insulin‐naïve T2D patients randomized to glargine were similar to those reported by Tang et al in insulin‐naïve T2D patients . Decreases in LFC have also been reported with other conventional basal insulins (including biphasic aspart 70/30 and biphasic lispro 75/25) in insulin‐naїve T2D patients. Among these studies, only Lingvay et al reported a statistically significant decrease in ALT with insulin treatment.…”

“…These results demonstrate that BIL, with reduced peripheral insulin activity (Fig. in) compared with glargine, does not decrease LFC, in contrast to several other basal insulins . Treatment with BIL resulted in higher LFC values compared to glargine in both T1D and T2D.…”

GLP-1 receptor agonist promotes brown remodelling in mouse white adipose tissue through SIRT1

“…This inconsistency reflects the different fat locations and individuals used in the studies. We studied epididymal fat, as exenatide has been revealed to reduce visceral rather than subcutaneous fat content [26]. The effect of GLP-1 on lipolysis might only exist in pathological conditions, and pharmacologically GLP-1 is likely to act in visceral rather than subcutaneous fat.…”

Liraglutide, Sitagliptin, and Insulin Glargine Added to Metformin: The Effect on Body Weight and Intrahepatic Lipid in Patients With Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease

“…The null hypothesis was that the treatment groups did not differ from each other with respect to the primary endpoint. A priori sample size calculations were based on the ability to detect an 18.6%, 18.6%, and 13.7% absolute clinical difference in liver fat before and after the intervention of liraglutide, sitagliptin, and insulin glargine, respectively . With a deviation estimate of 5.5% obtained from a similar study, we estimated that 22 patients in each group would be required, for a total of 66 patients (α = 0.05, β = 0.15).…”