Glucagon-like peptide-1 (GLP-1) is a 30-amino acid peptide hormone that is mainly expressed in the intestine and hypothalamus. In recent years, basic and clinical studies have shown that GLP-1 is closely related to lipid metabolism, and it can participate in lipid metabolism by inhibiting fat synthesis, promoting fat differentiation, enhancing cholesterol metabolism, and promoting adipose browning. GLP-1 plays a key role in the occurrence and development of metabolic diseases such as obesity, nonalcoholic fatty liver disease, and atherosclerosis by regulating lipid metabolism. It is expected to become a new target for the treatment of metabolic disorders. The effects of GLP-1 and dual agonists on lipid metabolism also provide a more complete treatment plan for metabolic diseases. This article reviews the recent research progress of GLP-1 in lipid metabolism.

Background/aim: Previous studies have suggested that the hepatic steatosis index (HSI) and fatty liver index (FLI) can be used as a predictor of non-alcoholic fatty liver disease (NAFLD). The aim of our study was to determine whether non-invasive indices of hepatic steatosis (HSI and FLI) are associated with carotid atherosclerosis in type 2 diabetes mellitus (T2DM).

Ectodysplasin A (EDA) is a member of the tumor necrosis factor (TNF) family of ligands that was initially reported to induce the formation of various ectodermal derivatives during normal prenatal development. EDA exerts its biological activity as two splice variants, namely, EDA-A1 and EDA-A2. The former binds to the EDA receptor (EDAR), resulting in the recruitment of the intracellular EDAR-associated death domain (EDARADD) adapter protein and the activation of the NF-κB signaling pathway, while the latter binds to a different receptor, EDA2R, also known as X-linked ectodermal dysplasia receptor (XEDAR). Inactivation mutation of the EDA gene or the genes coding for its receptors can result in hypohidrosis ectodermal dysplasia (HED), a condition that is characterized by oligotrichosis, edentulosis or oligodontia, and oligohidrosis or anhidrosis. Recently, as a new liver factor, EDA is gradually known and endowed with some new functions. EDA levels were observed to be upregulated in several metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance. In addition, EDA and its receptors have been implicated in tumor pathogenesis through the regulation of tumor cell proliferation, apoptosis, differentiation, and migration. Here, we first review the role of EDA and its two-receptor system in various signaling pathways and then discuss the physiological and pathological roles of EDA and its receptors.

Aims/hypothesis: The aim of this study was to evaluate the efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes insufficiently controlled with diet and exercise alone. Methods: The Peptide Innovation for Early Diabetes Treatment (PIONEER) 11 trial was a double-blind, randomised, Phase IIIa trial conducted across 52 sites in the China region (mainland China and Taiwan), Hungary, Serbia and Ukraine. Eligible participants were ≥18 years (≥20 years in Taiwan), had a diagnosis of type 2 diabetes with HbA_1c 53–86 mmol/mol (7.0–10.0%) and were not receiving any glucose-lowering drugs. After a 4-week run-in period in which participants were treated with diet and exercise alone, those who fulfilled the randomisation criteria were randomised (1:1:1:1) using a web-based randomisation system to receive once-daily oral semaglutide 3 mg, 7 mg or 14 mg or placebo for 26 weeks (using a 4-week dose-escalation regimen for the higher doses). Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary and confirmatory secondary endpoints were change from baseline to week 26 in HbA_1c and body weight (kg), respectively. Safety was assessed in all participants exposed to at least one dose of the trial product. Results: Between October 2019 and October 2021, a total of 774 participants were screened and 521 participants were randomised to oral semaglutide 3 mg (n=130), 7 mg (n=130), 14 mg (n=130) or placebo (n=131); most participants (92.5%, n=482) completed the trial, with 39 participants prematurely discontinuing treatment. The number of participants contributing to the trial analyses was based on the total number of participants who were randomised at the beginning of the trial. The majority of participants were male (63.7%), and the mean age of participants was 52 years. At baseline, mean HbA_1c and body weight were 63 mmol/mol (8.0%) and 79.6 kg, respectively. Oral semaglutide resulted in significantly greater reductions in HbA_1c than placebo at week 26 (p<0.001 for all doses). The estimated treatment differences (ETDs [95% CIs]) for oral semaglutide 3 mg, 7 mg and 14 mg vs placebo were –11 (–13, –9) mmol/mol, –16 (–18, –13) mmol/mol and –17 (–19, –15) mmol/mol, respectively. The corresponding ETDs in percentage points (95% CI) vs placebo were –1.0 (–1.2, –0.8), –1.4 (–1.6, –1.2) and –1.5 (–1.8, –1.3), respectively. Significantly greater reductions in body weight were also observed for oral semaglutide 7 mg and 14 mg than for placebo at week 26 (ETD [95% CI] –1.2 kg [–2.0 kg, –0.4 kg; p<0.01] and –2.0 kg [–2.8 kg, –1.2 kg; p<0.001], respectively), but not for oral semaglutide 3 mg (ETD [95% CI] –0.0 kg [–0.9 kg, 0.8 kg; not significant]). Similar reductions in HbA_1c and body weight were observed in the Chinese subpopulation, which represented 74.9% of participants in the overall population. Adverse events (AEs) occurred in between 65.4% and 72.3% of participants receiving oral semaglutide (for all doses) and 57.3% of participants with placebo. Most AEs were mild to moderate in severity, with few serious AEs reported; the most commonly reported AEs were gastrointestinal-related and were more frequent with semaglutide (all doses) than with placebo. The proportion of AEs was slightly higher in the Chinese subpopulation. Conclusions/interpretation: Oral semaglutide resulted in significantly greater reductions in HbA_1c across all doses and in significant body weight reductions for the 7 mg and 14 mg doses when compared with placebo in predominantly Chinese participants with type 2 diabetes insufficiently controlled by diet and exercise alone. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials. Trial registration: ClinicalTrials.gov NCT04109547. Funding: Novo Nordisk A/S. Graphical

Sleep plays a crucial biological role, and mounting evidence suggests that sleep disorders negatively impact health. In contemporary society, sleep disorders, such as sleep deprivation, insomnia, disrupted sleep-wake disorders, and circadian rhythm disorders, are widespread. Sleep disorders affect hormone production and secretion, which lead to endocrine changes, including impaired glucose tolerance, decreased insulin sensitivity, hepatic steatosis, and increased inflammatory responses, all of which accelerate the onset of various diseases. To support optimal metabolic and cardiovascular health, maintaining a consistent sleep schedule and practicing good sleep hygiene are essential.

Except for improving glycemic control, liraglutide, one of the glucagon-like peptide-1 receptor agonists, has exerted promising therapeutic effects for dyslipidemia. It has been proved that gut microbiota plays a dramatic role in regulating lipid metabolism. This study aims to explore whether liraglutide could improve dyslipidemia by modulating the gut microbiota in mice fed a high-fat diet (HFD). The C57BL/6 mice were fed a HFD to establish an animal model of dyslipidemia, and then administered with liraglutide or normal saline (NS) for 12 weeks. Indices of glucolipid metabolism were evaluated. Gut microbiota of the mice was analyzed by 16S rRNA gene sequencing. Compared with HFD group, liraglutide significantly alleviated weight, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels, meanwhile elevating high-density lipoprotein cholesterol (HDL) levels (all p < 0.05). The gut microbiota analysis revealed that liraglutide greatly reduced the relative abundance of Firmicutes and augmented that of Bacteroidetes, with a concomitant drop in the Firmicutes/Bacteroidetes ratio. Meanwhile, liraglutide dramatically changed the overall composition, promoted the growth of beneficial microbes (Akkermansia, Lactobacillus, Parabacteroides, Oscillospira, etc.), and inhibited the growth of harmful microbes (AF12, Shigella, Proteobacteria, Xenorhabdus, etc.). Especially, the relative abundance of Akkermansia increased the most after liraglutide treatment. Correlation analysis suggested that TC and LDL were positively correlated with some harmful bacteria, and negatively associated with beneficial bacteria. This study confirmed that liraglutide had a certain therapeutic effect on dyslipidemia in HFD-fed mice and could regulate the composition of the gut microbiota associated with lipid metabolism, especially Akkermansia. Thus, affecting gut microbiota might be a potential mechanism of liraglutide in attenuating dyslipidemia.