Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have emerged as a promising therapeutic option beyond their established role in managing type 2 diabetes mellitus (T2DM) and obesity. Recent research has highlighted their beneficial effects on liver, kidney, and cardiovascular health, mediated by both direct and indirect mechanisms. In the liver, GLP-1 RAs contribute to the improvement of metabolic dysfunction-associated steatotic liver disease (MASLD) by reducing hepatic fat accumulation, inflammation, and oxidative stress. Additionally, they enhance insulin sensitivity and lipid metabolism. Similarly, in diabetic kidney disease (DKD), GLP-1 RAs exhibit renoprotective properties by mitigating inflammation, oxidative stress, and glomerular hypertension. Furthermore, they promote natriuresis and stabilize renal function. Moreover, GLP-1 RAs present significant cardiovascular benefits, including improved myocardial function, reduced atherosclerosis progression, enhanced endothelial health, and decreased major adverse cardiovascular events (MACEs). Additionally, emerging evidence suggests GLP-1 RAs may exert substantial neuropsychiatric benefits, including reductions in depressive symptoms, anxiety, substance use behaviors, and lowering the risk of Alzheimer’s disease, Parkinson’s disease, and other dementias likely mediated by the modulation of neurotransmitter systems and neuroinflammation. Genetic polymorphisms in the GLP1R gene also impact the therapeutic response, highlighting the importance of personalized medicine in optimizing GLP-1 RA efficacy. This review synthesizes preclinical and clinical evidence supporting the multifaceted effects of GLP-1 RAs across multiple organ systems, highlighting their therapeutic potential beyond glycemic control. As research advances, further exploration of their mechanisms of action and long-term clinical outcomes, safety and effectiveness across diverse patient populations will be essential in optimizing their use in treating metabolic and neuropsychiatric conditions.

Colistin (polymyxin E), a last-resort antibiotic for the treatment of multidrug-resistant Gram-negative bacterial infections, is becoming increasingly compromised by the rapid emergence and dissemination of resistance. The extensive use of colistin in agriculture and veterinary medicine has accelerated the spread of plasmid-mediated mobile colistin resistance (mcr) genes, facilitating transmission across human, animal, and environmental reservoirs. This review provides a comprehensive overview of the epidemiology, molecular mechanisms, and geographical distribution of colistin resistance in the Middle East and North Africa (MENA) region. Analysis of the available literature indicates that Tunisia reports the highest prevalence of colistin-resistant Gram-negative bacteria in North Africa (58.09%), followed by Egypt (24.76%), Algeria (14.29%), and Libya (2.86%). Across the region, mcr-1 is the predominant plasmid-mediated resistance determinant, whereas chromosomal alterations involving the mgrB, pmrA/pmrB, and phoP/phoQ regulatory systems are the principal non-plasmid-mediated mechanisms. Resistance has been documented in major clinical pathogens, including Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, as well as in livestock, poultry, aquaculture, wildlife, food products, and environmental samples, highlighting the interconnected nature of resistance transmission under a One Health framework. The evidence demonstrates substantial geographical variability and significant gaps in surveillance across several MENA countries, limiting accurate regional burden estimates. Strengthening antimicrobial stewardship, harmonized surveillance programs, molecular monitoring of resistance determinants, and the implementation of One Health strategies are essential to limit the continued emergence and dissemination of colistin resistance throughout the region.