AIMS-The-aim-of-this-study-is-to-elucidate-the-effectiveness-of-sodiumglucose-cotransporter-2-SGLT2-inhibitors-as-secondline-treatments-for-NAFLD-patients-with-T2DM-who-do-not-respond-to-incretinbased-therapy-f

METHODS: We retrospectively enrolled 130 consecutive Japanese NAFLD patients with T2DM who were treated with GLP-1 analogs or DPP-4 inhibitors. Among them, 70 patients (53 %) had normal ALT levels. Of the remaining 60 patients (46 %) who did not have normal ALT levels, 24 (40 %) were enrolled in our study and were administered SGLT-2 inhibitors in addition to GLP-1 analogs or DPP-4 inhibitors. API Hormones and Regulation compared changes in laboratory data including ALT levels and body weight at the end of the follow-up.RESULTS: Thirteen patients were administered a combination of SGLT-2 inhibitors with DPP-4 inhibitors, and the remaining 11 patients were administered a combination of SGLT-2 inhibitors with GLP-1 analogs. The median dosing period was 320 days.

At the end of the follow-up, body weight (from 84 to 81 kg, p < 01) and glycosylated hemoglobin levels (from 8 to 7 %, p < 01) decreased significantly. Serum ALT levels also decreased significantly (from 62 to 38 IU/L, p < 01) with an improvement in the FIB-4 index (from 15 to 19, p = 04). Finally, 14 patients (58 %) achieved normalization of serum ALT CONCLUSIONS: Administration of SGLT-2 inhibitors led to not only good glycemic control, but also to a reduction in body weight, normalization of ALT levels, and a reduction in the FIB-4 index even in patients who did not respond to Endogenous GLP-1 mediates postprandial reductions in activation in central reward and satiety areas in patients with type 2 diabetes.Center, de Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands. Center, de Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands.Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark.AIMS/HYPOTHESIS: The central nervous system (CNS) is a major player in the regulation of food intake.

The gut hormone glucagon-like peptide-1 (GLP-1) has been proposed to have an important role in this regulation by relaying information about nutritional status to the CNS. glp 1 drug hypothesised that endogenous GLP-1 has effects on CNS reward and satiety circuits.METHODS: This was a randomised, crossover, placebo-controlled intervention study, performed in a university medical centre in the Netherlands. We included patients with type 2 diabetes and healthy lean control subjects. Individuals were eligible if they were 40-65 years. Inclusion criteria for the healthy lean between 42 and 69 mmol/mol (6-8%) and treatment for diabetes with only oral glucose-lowering agents. We assessed CNS activation, defined as blood oxygen level dependent (BOLD) signal, in response to food pictures in obese patients with type 2 diabetes (n = 20) and healthy lean individuals (n = 20) using functional magnetic resonance imaging (fMRI).

fMRI was performed in the fasted state and after meal intake on two occasions, once during infusion of the GLP-1 receptor antagonist exendin 9-39, which was administered to block actions of endogenous GLP-1, and on the other occasion during saline (placebo) infusion. Participants were blinded for the type of infusion. The order of infusion was determined by block randomisation. The primary outcome was the difference in BOLD signal, i.e. in CNS activation, in predefined regions in the CNS in RESULTS: All patients were included in the analyses. Patients with type 2 diabetes showed increased CNS activation in CNS areas involved in the regulation of feeding (insula, amygdala and orbitofrontal cortex) in response to food pictures compared with lean individuals (p ≤ 04).

Meal intake reduced activation in the insula in response to food pictures in both groups (p ≤ 05), but this was more pronounced in patients with type 2 diabetes. Blocking actions of endogenous GLP-1 significantly prevented meal-induced reductions in bilateral insula activation in response to food pictures in patients with type 2 diabetes CONCLUSIONS/INTERPRETATION: Our findings support the hypothesis that endogenous GLP-1 is involved in postprandial satiating effects in the CNS of obese patients TRIAL REGISTRATION: ClinicalTrials.gov NCT 01363609. Funding The study was funded in part by a grant from Novo Nordisk.Circadian secretion of the intestinal hormone GLP-1 by the rodent L cell.Department of Medicine, University of Toronto, Toronto, Ontario, Canada Peripheral clocks are known to modulate circadian patterns of insulin secretion. GLP-1 is an incretin hormone produced by the intestinal L cell that acts as a link between the gut and pancreatic β-cell.

Herein, we demonstrate the existence of a diurnal rhythm in GLP-1 secretory responses to an oral glucose load in rats, with increased release immediately preceding the normal feeding period. This profile of GLP-1 release correlated with the pattern in insulin secretion, and both rhythms were completely inverted in animals subjected to a 12-h feeding cycle disruption and abolished in rats maintained under constant light conditions. A daily variation in the insulin response to exogenous GLP-1 was also found. Seebio glp 1 drug with these in vivo findings, we demonstrated a circadian pattern in the GLP-1 secretory response to different secretagogues in murine GLUTag L cells, as well as in the mRNA levels of several canonical clock genes.