Metformin, a widely prescribed medication for type 2 diabetes, has garnered increasing attention for its potential neuroprotective properties due to the growing demand for treatments for Alzheimer’s, Parkinson’s, and motor neuron diseases. This review synthesizes experimental and clinical studies on metformin’s mechanisms of action and potential therapeutic benefits for neurodegenerative disorders. A comprehensive search of electronic databases, including PubMed, MEDLINE, Embase, and Cochrane library, focused on key phrases such as “metformin”, “neuroprotection”, and “neurodegenerative diseases”, with data up to September 2023. Recent research on metformin’s glucoregulatory mechanisms reveals new molecular targets, including the activation of the LKB1–AMPK signaling pathway, which is crucial for chronic administration of metformin. The pleiotropic impact may involve other stress kinases that are acutely activated. The precise role of respiratory chain complexes (I and IV), of the mitochondrial targets, or of the lysosomes in metformin effects remains to be established by further research. Research on extrahepatic targets like the gut and microbiota, as well as its antioxidant and immunomodulatory properties, is crucial for understanding neurodegenerative disorders. Experimental data on animal models shows promising results, but clinical studies are inconclusive. Understanding the molecular targets and mechanisms of its effects could help design clinical trials to explore and, hopefully, prove its therapeutic effects in neurodegenerative conditions.

Background: The underutilization of primary care services is a possible factor influencing inappropriate emergency service presentations. The objective of this study was to evaluate the proportion and characteristics of patients inappropriately accessing emergency room services from the perspective of primary care underutilization. Methods: This cross-sectional study included patients who visited the emergency room of a County Hospital, initially triaged with green, blue, or white codes, during a 2-week period in May 2017. Two primary care physicians performed a structured analysis to correlate the initial diagnosis in the emergency room with the final diagnosis to establish whether the patient’s medical complaints could have been resolved in primary care. Results: A total of 1269 adult patients were included in this study. In total, the medical problems of 71.7% of patients could have been resolved by a primary care physician using clinical skills, extended resources, or other ambulatory care and out-of-hours services. Conclusions: Low awareness of out-of-hours centers and a lack of resources for delivering more complex services in primary care can lead to inappropriate presentations to the emergency services. Future research on this topic needs to be conducted at the national level.

Background: Polypharmacy is widespread among older adults and presents significant clinical challenges. Although necessary for managing multimorbidity, inappropriate polypharmacy is linked to adverse drug reactions, drug–drug interactions, cognitive decline, and increased health care utilization. Interventions such as deprescribing and medication reviews aim to mitigate these risks, but their effectiveness in improving clinical outcomes remains uncertain. Areas of Uncertainty: Despite reductions in potentially inappropriate medications, polypharmacy interventions show a limited impact on mortality, hospitalization rates, and quality of life. Variability in intervention intensity, poor implementation strategies, and a lack of integration between pharmacists and prescribers contribute to inconsistent findings. In addition, current deprescribing approaches often fail to account for patient priorities, multimorbidity, and real-world feasibility in primary care settings. Data Sources: This review synthesizes findings from systematic reviews, randomized controlled trials, and meta-analyses evaluating polypharmacy interventions and their clinical impact. Therapeutic Advances: Medication reviews using STOPP/START, Beers Criteria, and Medication Appropriateness Index improve prescribing quality but require a shift toward comprehensive clinical medication reviews. High-intensity interventions involving multidisciplinary teams, including clinical pharmacologists, show promise in reducing hospitalizations and adverse drug reactions. Emerging strategies such as shared decision making, digital deprescribing tools, and artificial intelligence–driven clinical decision support systems may enhance polypharmacy management. Conclusions: To improve clinical outcomes, future polypharmacy interventions must emphasize structured implementation, real-world adaptability, and patient-centered approaches. Integrating clinical pharmacologists, strengthening pharmacist–prescriber collaboration, and leveraging technology will be essential for optimizing medication use in older adults.