Metformin: Is it a drug for all reasons and diseases?

Metformin was first used to treat type 2 diabetes in the late 1950s and in 2022 remains the first-choice drug used daily by approximately 150 million people. An accumulation of positive pre-clinical and clinical data has stimulated interest in re-purposing metformin to treat a variety of diseases including COVID-19. In polycystic ovary syndrome metformin improves insulin sensitivity. In type 1 diabetes metformin may help reduce the insulin dose. Meta-analysis and data from pre-clinical and clinical studies link metformin to a reduction in the incidence of cancer. Clinical trials, including MILES (Metformin In Longevity Study), and TAME (Targeting Aging with Metformin), have been designed to determine if metformin can offset aging and extend lifespan. Pre-clinical and clinical data suggest that metformin, via suppression of pro-inflammatory pathways, protection of mitochondria and vascular function, and direct actions on neuronal stem cells, may protect against neurodegenerative diseases. Metformin has also been studied for its anti-bacterial, -viral, -malaria efficacy. Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an anti-hyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct anti-viral actions. Clarification is also sought as to whether data from ex vivo studies based on the use of high concentrations of metformin can be translated into clinical benefits, or whether they reflect a 'Paracelsus' effect. The environmental impact of metformin, a drug with no known metabolites, is another emerging issue that has been linked to endocrine disruption in fish, and extensive use in T2D has also raised concerns over effects on human reproduction. The objectives for this review are to: 1) evaluate the putative mechanism(s) of action of metformin; 2) analyze the controversial evidence for metformin's effectiveness in the treatment of diseases other than type 2 diabetes; 3) assess the reproducibility of the data, and finally 4) reach an informed conclusion as to whether metformin is a drug for all diseases and reasons. We conclude that the primary clinical benefits of metformin result from its insulin-sensitizing and antihyperglycaemic effects that secondarily contribute to a reduced risk of a number of diseases and thereby enhancing healthspan. However, benefits like improving vascular endothelial function that are independent of effects on glucose homeostasis add to metformin's therapeutic actions.

Perceptions and experiences toward extended-release buprenorphine among persons leaving jail with opioid use disorders before and during COVID-19: An in-depth qualitative study

Background: Extended-release buprenorphine (XRB) offers a novel approach to sustained monthly treatment for people who use opioids in criminal justice settings (CJS). This study explores the experiences of adults receiving XRB as a jail-to-community treatment. Methods and findings: In-depth qualitative interviews were conducted among adult participants with opioid use disorder (OUD;n = 16) who were recently released from NYC jails and maintained on XRB after switching from daily sublingual buprenorphine (SLB). Interviews elaborated on the acceptability and barriers and facilitators of XRB treatment pre- and post-release. Interviews were audio recorded, transcribed, and analyzed for content related to factors influencing XRB treatment uptake and community reentry. Important themes were grouped into systems, medication, and patient-level factors. Key systems-level factors influencing initiation of XRB in jail included an alternative to perceived stigmatization and privacy concerns associated with daily in-jail SLB administration and less concerns with buprenorphine diversion. In-jail peer networks positively influenced participant adoption of XRB. XRB satisfaction was attributed to reduced in-jail clinic and medication administration visits, perceived efficacy and blockade effects upon the use of heroin/fentanyl following release, and averting the risk of criminal activities to fund opioid use. Barriers to retention included post-injection withdrawal symptoms and cravings attributed to perceived suboptimal medication dosing, injection site pain, and lack of in-jail provider information about the medication. Conclusion: Participants were generally favorable to XRB initiation in jail and retention post-release. Further studies are needed to address factors influencing access to XRB in criminal justice settings, including stigma, ensuring patient privacy following initiation on XRB, and patient-, provider-, and correctional staff education pertaining to XRB. Trial Registration: ClinicalTrials.gov Identified: NCT03604159. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Requiem for impact factors and high publication charges.

Journal impact factors, publication charges and assessment of quality and accuracy of scientific research are critical for researchers, managers, funders, policy makers, and society. Editors and publishers compete for impact factor rankings, to demonstrate how important their journals are, and researchers strive to publish in perceived top journals, despite high publication and access charges. This raises questions of how top journals are identified, whether assessments of impacts are accurate and whether high publication charges borne by the research community are justified, bearing in mind that they also collectively provide free peer-review to the publishers. Although traditional journals accelerated peer review and publication during the COVID-19 pandemic, preprint servers made a greater impact with over 30,000 open access articles becoming available and accelerating a trend already seen in other fields of research. We review and comment on the advantages and disadvantages of a range of assessment methods and the way in which they are used by researchers, managers, employers and publishers. We argue that new approaches to assessment are required to provide a realistic and comprehensive measure of the value of research and journals and we support open access publishing at a modest, affordable price to benefit research producers and consumers.

COVID-19 in the New York City Jail System: Epidemiology and Health Care Response, March-April 2020.

OBJECTIVES: People detained in correctional facilities are at high risk for infection with severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019 (COVID-19). We described the epidemiology of the COVID-19 outbreak in a large urban jail system, including signs and symptoms at time of testing and risk factors for hospitalization. METHODS: This retrospective observational cohort study included all patients aged ≥18 years who were tested for COVID-19 during March 11-April 28, 2020, while in custody in the New York City jail system (N = 978). We described demographic characteristics and signs and symptoms at the time of testing and performed Cox regression analysis to identify factors associated with hospitalization among those with a positive test result. RESULTS: Of 978 people tested for COVID-19, 568 received a positive test result. Among symptomatic patients, the most common symptoms among those who received a positive test result were cough (n = 293 of 510, 57%) and objective fever (n = 288 of 510, 56%). Of 257 asymptomatic patients who were tested, 58 (23%) received a positive test result. Forty-five (8%) people who received a positive test result were hospitalized for COVID-19. Older age (aged ≥55 vs 18-34) (adjusted hazard ratio [aHR] = 13.41; 95% CI, 3.80-47.33) and diabetes mellitus (aHR = 1.99; 95% CI, 1.00-3.95) were significantly associated with hospitalization. CONCLUSIONS: A substantial proportion of people tested in New York City jails received a positive test result for COVID-19, including a large proportion of people tested while asymptomatic. During periods of ongoing transmission, asymptomatic screening should complement symptom-driven COVID-19 testing in correctional facilities. Older patients and people with diabetes mellitus should be closely monitored after COVID-19 diagnosis because of their increased risk for hospitalization.