Effects of sitagliptin on ectopic fat contents and glucose metabolism in type 2 diabetic patients with fatty liver: A pilot study

Abstract

Aims/IntroductionRecent data have shown that ectopic fat accumulation in the liver worsens hepatic glucose metabolism, suggesting that fatty liver in patients with type 2 diabetes is a therapeutic target. Glucagon-like peptide (GLP)-1 improves fatty liver, but the effect of dipeptidyl peptidase-4 inhibitor on fatty liver is still unclear. The present pilot study determined the effects of 12-week treatment with sitagliptin, a dipeptidyl peptidase-4 inhibitor, on liver fat content in type 2 diabetes with fatty liver. We also evaluated intramyocellular lipid (IMCL) and glucose kinetics during oral glucose tolerance test (OGTT) before and after the treatment.Materials and MethodsThe study participants were seven type 2 diabetes patients with fatty liver who were studied at baseline and 12 weeks after sitagliptin treatment. Intrahepatic lipid (IHL) and IMCL were assessed by 1H magnetic resonance spectroscopy. Glucose kinetics was assessed during double-tracer OGTT (U-[13C]-glucose orally and 6,6-[2H2]-glucose intravenously).ResultsSitagliptin significantly reduced glycated hemoglobin (from 7.1 ± 0.2 to 6.5 ± 0.3%, P < 0.005), but had no effects on IHL and IMCL. The glucose level diminished, whereas GLP-1 concentration increased during OGTT at the end of treatment. These changes were not accompanied by significant changes in insulin or glucagon levels. However, long-term sitagliptin treatment partially decreased the rate of appearance of oral glucose during OGTT, but did not affect endogenous glucose production or the rate of disappearance.ConclusionsIt was found that 12-week sitagliptin treatment improved glycated hemoglobin and glucose excursion during OGTT in type 2 diabetes with fatty liver, independent of changes in lipid accumulation in the liver. This trial was registered with the Japan Clinical Trials Registry (UMIN-CTR000005666).

Dipeptidyl peptidase 4 inhibitors attenuates the decline of skeletal muscle mass in patients with type 2 diabetes

“…When considering the effects of DPP4 inhibitors on visceral and subcutaneous fat accumulation, we did not find any significant association either in the overall population (Table ) or in the PS matching population (Table ). Our data are consistent with a previous report showing that sitagliptin did not significantly reduce visceral and subcutaneous fat mass measured by magnetic resonance imaging in patients with type 2 diabetes with fatty liver . Rats of DPP4 deficiency fed with high fat diet (HFD) were shown to gain more weight and visceral fat accumulation than control rats fed with HFD, although lack of DPP4 enzyme attenuated HFD‐induced insulin resistance, reduces adipose tissue inflammation, reduces macrophage infiltration, and enhances adiponectin .…”

Impaired peripheral insulin sensitivity in non‐obese Japanese patients with type 2 diabetes mellitus and fatty liver

“…Blood samples were obtained for biochemical analysis at 10 min intervals during the last 30 min at baseline and steady state during the clamp study. The enrichment of 6,6‐[ 2 H 2 ]glucose in plasma was determined as previously described . The rates of endogenous glucose production (EGP) and glucose disposal (Rd) during the clamp study were evaluated by a steady‐state equation .…”

Gut-Pancreas-Liver Axis as a Target for Treatment of NAFLD/NASH

“…The improvement in hepatic histology was correlated to the reduction in BMI and serum AST and ALT levels. However, the reduction in steatosis score was of borderline statistical significance and no change was observed in either liver fibrosis or lobular inflammation [115,148] (Table 2). The available data suggest that treatment with DPP-4 inhibitors may have a mild beneficial effect on NAFLD, probably mediated by the increase in GLP-1 concentrations after blocking DPP-4 activity.…”