Renal cell carcinoma (RCC) represents 85–95% of kidney cancers and is the most frequent type of renal cancer in adult patients. It accounts for 3% of all cancer cases and is in 7th place among the most frequent histological types of cancer. Clear cell renal cell carcinoma (ccRCC), accounts for 75% of RCCs and has the most kidney cancer-related deaths. One-third of the patients with ccRCC develop metastases. Renal cancer presents cellular alterations in sugars, lipids, amino acids, and nucleic acid metabolism. RCC is characterized by several metabolic dysregulations including oxygen sensing (VHL/HIF pathway), glucose transporters (GLUT 1 and GLUT 4) energy sensing, and energy nutrient sensing cascade. Metabolic reprogramming represents an important characteristic of the cancer cells to survive in nutrient and oxygen-deprived environments, to proliferate and metastasize in different body sites. The phosphoinositide 3-kinase-AKT-mammalian target of the rapamycin (PI3K/AKT/mTOR) signaling pathway is usually dysregulated in various cancer types including renal cancer. This molecular pathway is frequently correlated with tumor growth and survival. The main aim of this review is to present renal cancer types, dysregulation of PI3K/AKT/mTOR signaling pathway members, crosstalk with VHL/HIF axis, and carbohydrates, lipids, and amino acid alterations.

Since we aim to test new options to find medication for cognitive disorders, we have begun to assess the effect of semaglutide and to conduct a review gathering studies that have attempted this purpose. This systematic review focuses on the cognitive effects of semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), in the context of neurological and cognitive impairment. Semaglutide, a synthetic GLP-1 analog, showcased neuroprotective effects beyond metabolic regulation. It mitigated apoptosis and improved cognitive dysfunction in cerebrovascular disease, suggesting broader implications for neurological well-being. Also, studies highlighted GLP-1 RAs’ positive impact on olfactory function in obese individuals with type 2 diabetes, on neurodegenerative disorders, multiple sclerosis, and endotoxemia. In order to analyze current studies that assess the impact of semaglutide on cognitive function, a literature search was conducted up to February 2024 on two online databases, MEDLINE (via PubMed) and Web of Science Core Collection, as well as various websites. Fifteen studies on mice populations and two studies on cell lines were included, analyzed, and assessed with bias-specific tools. The neuroprotective and anti-apoptotic properties of GLP-1 and its analogs were emphasized, with animal models and cell line studies demonstrating enhanced cognitive function. While promising, limitations include fewer studies, highlighting the need for extensive research, particularly in the human population. Even though this medication seems promising, there are significant limitations, one of which is the lack of studies on human subjects. Therefore, this review aims to gather current evidence.

Background/Objectives: Type 2 diabetes mellitus (T2DM) has been evaluated through a glucocentric model centered on hyperglycemia, glycated haemoglobin (HbA1c) targets, and complications. However, obesity-associated T2DM reflects a broader metabolic ecosystem in which glycemic control interacts with adiposity, inflammation, muscle function, renal stability, and treatment mechanisms. Therapeutic response may be better captured through patient-level responder phenotypes than through mean changes in isolated outcomes. We aimed to determine, in adults with obesity-associated T2DM maintained on stable 12-month metformin-based regimens, the distribution of concordant versus discordant glycemic–adiposity response phenotypes and the frequency of high multidimensional response, and to describe how these phenotypes were distributed across treatment classes. Methods: This secondary patient-level analysis used a real-world cohort from a Bucharest tertiary diabetes center. Of 291 screened adults, 166 completed 12-month follow-up without treatment change. Regimens included metformin alone or combined with sulfonylurea, DPP-4 inhibitor, SGLT2 inhibitor, GLP-1 receptor agonist, or insulin. Responses were defined as HbA1c reduction ≥ 0.5 percentage points, fat mass reduction ≥ 5%, hs-CRP reduction ≥ 20%, and handgrip strength decline ≤ 1 kg. Primary phenotypes and a 0–4 multidimensional score were derived. Results: Mean age was 59.7 ± 13.0 years, BMI 36.3 ± 4.4 kg/m², and baseline HbA1c 8.9 ± 1.0%. Glycemic–adiposity, glycemic-only, adiposity-only, and low/non-response phenotypes occurred in 49 (29.5%), 88 (53.0%), 9 (5.4%), and 20 (12.0%) patients, respectively. A high multidimensional response occurred in 78 (47.0%), and complete response in 25 (15.1%). GLP-1 receptor agonists showed the most consistent concordant glycemic–adiposity response, whereas insulin was predominantly glycemic-only. Conclusions: In obesity-associated T2DM, therapeutic response was heterogeneous and frequently discordant across metabolic domains. Patient-level responder phenotyping may complement conventional HbA1c-centered evaluation by identifying response quality across glycemic, adiposity, inflammatory, and functional dimensions. This approach may support more individualized diagnostic interpretation and treatment optimization in real-world diabetes care.

The present study aimed to analyse the published data and to realize an update about the use and pathogenesis of the novel antidiabetic drugs, respectively, dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 Ra), and sodium-glucose co-transporter-2 inhibitors (SGLT-2i), in patients with type 2 diabetes mellitus (T2DM) and coronavirus disease (COVID-19). Literature research in the PubMed and Web of Science database was performed in order to identify relevant published clinical trials and meta-analyses that include information about the treatment with novel antidiabetic agents in patients with T2DM and COVID-19. A total of seven articles were included, and their primary and secondary outcomes were reported and analysed. DPP-4i has mixed results on mortality in T2DM patients with COVID-19 but with an overall slightly favourable or neutral effect, whereas GLP-1 Ra seems to have a rather beneficial impact, while SGLT-2i may be useful in acute illness. Even if there are limited data, they seem to have favourable efficacy and safety profiles. The available evidence is heterogenous and insufficient to evaluate if the benefits of non-insulin novel antidiabetic drugs in COVID-19 treatment are due to the improvement of glycaemic control or to their intrinsic anti-inflammatory effects but highlights their beneficial effects in the pathogenesis and evolution of the disease.

Background and Objectives: The management of type 2 diabetes (T2D) extends beyond glycemic control, requiring a more global strategy that includes optimization of body composition, even more so in the context of sarcopenia and visceral adiposity, as they contribute to poor outcomes. Past reviews have typically been focused on weight reduction or glycemic effectiveness, with limited inclusion of new therapies’ effects on muscle and fat distribution. In addition, the emergence of incretin-based therapies and dual agonists such as tirzepatide requires an updated synthesis of their impacts on body composition. This review attempts to bridge the gap by taking a systematic approach to how current blood-glucose lowering therapies affect lean body mass, fat mass, and the risk of sarcopenia in T2D patients. Materials and Methods: Between January 2015 and March 2025, we conducted a narrative review by searching the PubMed, Scopus, and Web of Science databases for English-language articles. The keywords were combinations of the following: “type 2 diabetes,” “lean body mass,” “fat mass,” “body composition,” “sarcopenia,” “GLP-1 receptor agonists,” “SGLT2 inhibitors,” “tirzepatide,” and “antidiabetic pharmacotherapy.” Reference lists were searched manually as well. The highest precedence was assigned to studies that aimed at adult type 2 diabetic subjects and reported body composition results. Inclusion criteria for studies were: (1) type 2 diabetic mellitus adult patients and (2) reporting measures of body composition (e.g., lean body mass, fat mass, or muscle function). We prioritized randomized controlled trials and large observational studies and excluded mixed diabetic populations, non-pharmacological interventions only, and poor reporting of body composition. Results: Metformin was widely found to be weight-neutral with minimal effects on muscle mass. Insulin therapy, being an anabolic hormone, often leads to fat mass accumulation and increases the risk of sarcopenic obesity. Incretin-based therapies induced substantial weight loss, mostly from fat mass. Notable results were observed in studies with tirzepatide, demonstrating superior reduction not only in fat mass, but also in visceral fat. Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) promote fat loss but are associated with a small yet significant decrease in lean muscle mass. Conclusions: Blood-glucose lowering therapies demonstrated clinically relevant effects on body composition. Treatment should be personalized, balancing glycemic control, cardiovascular, and renal benefits, together with optimal impact on muscle mass along with glycemic, cardiovascular, and renal benefits.

Background and Objectives: The primary objective of this study was to investigate the incidence of lower extremity amputations (LEAs) in a representative population from Romania, in both diabetic and non-diabetic adults, including trauma-related amputations. The secondary objective was to evaluate the trends in LEAs and the overall ratio of major-to-minor amputations. Material and Methods: The study was retrospective and included data from the Romanian National Hospital Discharge Records, conducted between 1 January 2015 and 31 December 2019. Results: The overall number of cases with LEAs was 88,102, out of which 38,590 were aterosclerosis-related LEAs, 40,499 were diabetes-related LEAs, and 9013 were trauma-related LEAs, with an ascending trend observed annually for each of these categories. Of the total non-traumatic amputations, 51.2% were in patients with diabetes. Most LEAs were in men. The total incidence increased from 80.61/100,000 in 2015 to 98.15/100,000 in 2019. Conclusions: Our study reported a 21% increase in total LEAs, 22.01% in non-traumatic LEAs, and 19.65% in trauma-related amputation. The minor-to-major amputation ratio increased over the study period in patients with diabetes. According to these findings, it is estimated that currently, in Romania, there is one diabetes-related amputation every hour and one non-traumatic amputation every 30 min.