Diabetes Mellitus (DM) is a multi-factorial chronic health condition that affects a large part of population and according to the World Health Organization (WHO) the number of adults living with diabetes is expected to increase. Since type 2 diabetes mellitus (T2DM) is suffered by the majority of diabetic patients (around 90–95%) and often the mono-target therapy fails in managing blood glucose levels and the other comorbidities, this review focuses on the potential drugs acting on multi-targets involved in the treatment of this type of diabetes. In particular, the review considers the main systems directly involved in T2DM or involved in diabetes comorbidities. Agonists acting on incretin, glucagon systems, as well as on peroxisome proliferation activated receptors are considered. Inhibitors which target either aldose reductase and tyrosine phosphatase 1B or sodium glucose transporters 1 and 2 are taken into account. Moreover, with a view at the multi-target approaches for T2DM some phytocomplexes are also discussed.

: The purpose of the article is to offer an overview of the latest release of the VEGA suite of programs. This software has been constantly developed and freely released during the last 20 years and has now reached a significant diffusion and technology level as confirmed by the about 22 500 registered users. While being primarily developed for drug design studies, the VEGA package includes cheminformatics and modeling features, which can be fruitfully utilized in various contexts of the computational chemistry. To offer a glimpse of the remarkable potentials of the software, some examples of the implemented features in the cheminformatics field and for structure-based studies are discussed. Finally, the flexible architecture of the VEGA program which can be expanded and customized by plug-in technology or scripting languages will be described focusing attention on the HyperDrive library including highly optimized functions. Availability and implementation: The VEGA suite of programs and the source code of the VEGA command-line version are available free of charge for non-profit organizations at http://www.vegazz.net.

Obesity and type 2 diabetes (T2DM) are major public health concerns associated with serious morbidity and increased mortality. Both obesity and T2DM are strongly associated with adiposopathy, a term that describes the pathophysiological changes of the adipose tissue. In this review, we have highlighted adipose tissue dysfunction as a major factor in the etiology of these conditions since it promotes chronic inflammation, dysregulated glucose homeostasis, and impaired adipogenesis, leading to the accumulation of ectopic fat and insulin resistance. This dysfunctional state can be effectively ameliorated by the loss of at least 15% of body weight, that is correlated with better glycemic control, decreased likelihood of cardiometabolic disease, and an improvement in overall quality of life. Weight loss can be achieved through lifestyle modifications (healthy diet, regular physical activity) and pharmacotherapy. In this review, we summarized different effective management strategies to address weight loss, such as bariatric surgery and several classes of drugs, namely metformin, GLP-1 receptor agonists, amylin analogs, and SGLT2 inhibitors. These drugs act by targeting various mechanisms involved in the pathophysiology of obesity and T2DM, and they have been shown to induce significant weight loss and improve glycemic control in obese individuals with T2DM.