IntroductionDiabetes mellitus (DM) is one of the most common comorbidities among patients with coronavirus disease 2019 (COVID-19) which may exacerbate complications of this new viral infection. Metformin is an anti-hyperglycemic agent with host-directed immune-modulatory effects, which relieve exaggerated inflammation and reduce lung tissue damage. The current systematic review aimed to summarize the available evidence on the potential mechanism of action and the efficacy of metformin in COVID-19 patients with DM.MethodsA systematic search was carried out in PubMed/Medline, EMBASE, the Cochrane Controlled Register of Trials (CENTRAL), and Web of Science up to July 30, 2020. The following keywords were used: “COVID-19”, “SARS-CoV-2”, “2019-nCoV”, “metformin”, and “antidiabetic drug”.ResultsFourteen studies were included in our systematic review. Three of them were observational with 6,659 participants. Decreasing insulin resistance, reduction of some inflammatory cytokines like IL-6 and TNF-α, modulation of angiotensin-converting enzyme 2 (ACE2) receptor, and improving neutrophil to lymphocyte ratio are some of the potential mechanisms of metformin in COVID-19 patients with DM. Nine out of fourteen articles revealed the positive effect of metformin on the prognosis of COVID-19 in diabetic or even non-diabetic patients. Moreover, different studies have shown that metformin is more effective in women than men.ConclusionsThe use of metformin may lead to improve the clinical outcomes of patients with mild to moderate SARS-CoV-2, especially in diabetic women. Further observational studies should be conducted to clarify the effects of metformin as a part of the treatment strategy of COVID-19.

BackgroundOpioid dependency is a chronic relapsing disorder for which different therapeutically interventions have been developed. Naltrexone is a non-selective opioid antagonist that can be utilized for maintenance therapy in opioid dependency. In this systematic review, we aimed to evaluate the effects of naltrexone on retention in treatment and being opioid-free.MethodsWe systematically searched PubMed and EMBASE databases up to February 5, 2022, using the following keywords: “Naltrexone,” “Substance abuse,” “Drug abuse,” “Opiate-related disorder,” and “Opioid dependence.” Studies that included opiate-dependent individuals who were treated with naltrexone and assessed retention in treatment or being opioid-free were included. Two authors independently used the Cochrane risk-of-bias tool for quality assessment. A random effect model in Comprehensive Meta-Analysis software was used for the conduction of the meta-analysis. We performed subgroup analysis to evaluate the effects of naltrexone types on outcomes.ResultsEighteen studies, including 2,280 participants met our inclusion criteria. The duration of treatment ranged from 21 days to 24 months. The retention in treatment with naltrexone was 63% higher than controls (odds ratio (OR): 1.64 [95% confidence interval (CI), 0.78–3.44]. The OR for being opioid-free was 1.63 (95% CI, 0.57–4.72). Injectable naltrexone was significantly effective on retention in treatment (OR 1.86; 95% CI, 1.17–2.98).ConclusionsWe found that naltrexone could be useful for retention in treatment and being opioid-free, however, the findings were not significant. Further high-quality and large-scale observational studies are recommended.