The available data suggest differences in the course of type 2 diabetes mellitus (T2DM) between men and women, influenced by the distinguishing features of the sex. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a relatively new class of antidiabetic drugs that act by mimicking the function of endogenous glucagon-like peptide 1. They constitute valuable agents for the management of T2DM as, in addition to exerting a strong hypoglycemic action, they present cardiorenal protective properties, promote weight loss, and have a good safety profile, particularly with respect to the risk of hypoglycemia. Due to the precedent of studies having identified sexual dimorphic elements regarding the action of other antidiabetic agents, ongoing research has attempted to examine whether this is also the case for GLP-1 RAs. Until now, sex differences have been observed in the impact of GLP1-RAs on glycemic control, weight reduction, and frequency of adverse events. On the contrary, the question of whether these drugs differentially affect the two sexes with respect to cardiovascular risk and incidence of major adverse cardiovascular events remains under investigation. Knowledge of the potential sex-specific effects of these medications is extremely useful for the implementation of individualized therapeutic plans in the treatment of T2DM. This narrative review aims to present the available data regarding the sex-specific action of GLP-1 RAs as well as to discuss the potential pathophysiologic mechanisms explaining these dissimilarities.

The worldwide incidence of type 1 diabetes mellitus (T1DM) has increased in recent decades. The reasons behind this phenomenon are not yet fully understood. Early life infections, prenatal and perinatal factors, and diet composition have been associated with the triggering of autoimmunity and the risk of presentation of T1DM. However, the rapid increase in new cases of the disease raises the hypothesis that lifestyle factors, which have traditionally been associated with type 2 diabetes, such as obesity and unhealthy eating patterns could also play a role in the genesis of autoimmune diabetes. This article aims to highlight the changing epidemiology of T1DM and the importance of properly recognizing the environmental factors behind it, as well as the connections with the pathogenesis of the disorder and the need to prevent or delay T1DM and its long-term complications.

For seven weeks, 37 overweight adults followed a hypocaloric diet based on Orthodox Fasting (OF). A hypocaloric, time restricted eating (TRE) plan (eating between 08:00 to 16:00 h, water fasting from 16:00 to 08:00 h) was followed by 23 Body Mass Index (BMI)-matched participants. Anthropometric, glycaemic and inflammation markers and serum lipids were assessed before and after the diets. Both OF and TRE groups demonstrated reductions in BMI (28.54 ± 5.45 vs 27.20 ± 5.10 kg/m², p < 0.001 and 26.40 ± 4.11 vs 25.81 ± 3.78 kg/m² p = 0.001, respectively). Following the intervention, the OF group presented lower concentrations of total and low-density lipoprotein-cholesterol, compared with the pre-fasting values (178.40 ± 34.14 vs 197.17 ± 34.30 mg/dl, p < 0.001 and 105.89 ± 28.08 vs 122.37 ± 29.70 mg/dl, p < 0.001, respectively). Neither group manifested significant differences in glycaemic and inflammatory parameters. Our findings suggest that OF has superior lipid lowering effects than the TRE pattern.

Hepatocellular carcinoma (HCC) is characterized by poor survival rate and quality of life, while available treatments remain generally limited. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) originally emerged as drugs for the management of diabetes, but have also been shown to alleviate cardiorenal risk. Furthermore, they have demonstrated a wide range of extraglycemic effects that led to their evaluation as potential therapies for a variety of diseases beyond diabetes, such as obesity, neurogenerative disorders and nonalcoholic fatty liver disease. Given the presence of the GLP-1 receptor in hepatocytes, animal data suggest that GLP-1 RAs could regulate molecular pathways that are deeply involved in the genesis and progression of HCC, including inflammatory responses, tumor cell proliferation and oxidative stress, through direct and indirect effects on liver cells. However, future studies must assess several aspects of the benefit-to-risk ratio of the use of GLP-1 RAs in patients with HCC, including co-administration with approved systemic therapies, the incidence of gastrointestinal side effects in a high-risk population, and weight loss management in individuals with poor nutritional status and high rates of cancer cachexia. In this narrative review, we discuss the potential role of GLP-1 analogs in the treatment of HCC, focusing on the molecular mechanisms that could justify a possible benefit, but also referring to the potential clinical implications and areas for future research.