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PloS One 2022Metformin has been suggested to reduce thyroid cancer incidence and to improve thyroid cancer prognosis. We aimed to evaluate the associations between metformin and... (Meta-Analysis)
Meta-Analysis
Metformin has been suggested to reduce thyroid cancer incidence and to improve thyroid cancer prognosis. We aimed to evaluate the associations between metformin and thyroid cancer incidence and prognosis (metastasis/recurrence/progression-free survival). Cochrane Library, PubMed, ClinicalTrials.gov, and U.S. National Library of Medicine Clinical Trials were searched through the end of December 2021. Data were collected from original observational studies or clinical trials on the incidence or prognosis of thyroid carcinoma outcomes in type 2 diabetes mellitus (T2DM) patients with and without metformin use. Risk of bias in non-randomized studies of interventions (ROBINS-I) tool and Grading of Recommendations, and Assessment, Development and Evaluations (GRADE) approach were used to evaluate the risk of bias and quality of the body of evidence, respectively. In general, 4 studies were related to the thyroid cancer incidence, including 1,705,123 participants metformin users and non-users and yielding a total of 3,238 thyroid cancer events; 3 studies reported the prognosis of thyroid carcinoma based on a total of 4,972 individuals with primary thyroid carcinoma and comorbid type 2 diabetes, and the number of thyroid cancer prognosis cases ranged from 3 to 79. The overall risk of bias of the included studies ranged from moderate to serious. In the random-effects model, the summary relative risk (SRR) for thyroid cancer incidence was 0.743 (95% CI: 0.453-1.220; I2 = 88.7%, low certainty) comparing metformin users to non-users; and SRR for the prognosis of thyroid cancer was 0.504 (95% CI: 0.178-1.430; I2 = 57.5%, low certainty). Non-statistically significant negative associations between metformin use and incidence and prognosis of thyroid cancer were found in the current analysis, although the quantity and quality of the evidence were limited. Futher investigation is needed to evaluate the clinical benefits of metformin on thyroid cancer prevention and treatments.
Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Incidence; Metformin; Thyroid Neoplasms
PubMed: 35901016
DOI: 10.1371/journal.pone.0271038 -
Nutrients Dec 2016The aim of this systematic review is to assess whether metformin could change the concentration of serum homocysteine (Hcy) with and without simultaneous supplementation... (Meta-Analysis)
Meta-Analysis Review
The aim of this systematic review is to assess whether metformin could change the concentration of serum homocysteine (Hcy) with and without simultaneous supplementation of B-group vitamins or folic acid. A literature search was conducted in PubMed, EmBase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials (RCTs) reporting the concentration of serum Hcy in metformin-treated adults. Meta-analysis was applied to assess the association between metformin and the changes of Hcy concentration. Twelve publications were included in this study. In the overall analysis, metformin administration was not statistically associated with the change of Hcy when compared with the control treatment (mean difference (MD), 0.40 μmol/L; 95% confidence interval (CI), -0.07~0.87 μmol/L, = 0.10). In the subgroup analysis, metformin was significantly associated with an increased concentration of Hcy in the absence of exogenous supplementation of folic acid or B-group vitamins (MD, 2.02 μmol/L; 95% CI, 1.37~2.67 μmol/L, < 0.00001), but with a decreased concentration of serum Hcy in the presence of these exogenous supplementations (MD, -0.74 μmol/L; 95% CI, -1.19~-0.30 μmol/L, = 0.001). Therefore, although the overall effect of metformin on the concentration of serum Hcy was neutral, our results suggested that metformin could increase the concentration of Hcy when exogenous B-group vitamins or folic acid supplementation was not given.
Topics: Folic Acid; Homocysteine; Hypoglycemic Agents; Metformin; Vitamin B Complex
PubMed: 27941660
DOI: 10.3390/nu8120798 -
Frontiers in Medicine 2021The coronavirus disease (COVID-19) pandemic is a critical public health issue. Evidence has shown that metformin favorably influences COVID-19 outcomes. This study...
The coronavirus disease (COVID-19) pandemic is a critical public health issue. Evidence has shown that metformin favorably influences COVID-19 outcomes. This study aimed to assess the benefits and risks of metformin in COVID-19 patients. We searched the PubMed, Embase, Cochrane Library, and Chinese Biomedical Literature Database from inception to February 18, 2021. Observational studies assessing the association between metformin use and the outcomes of COVID-19 patients were included. The primary outcome was mortality, and the secondary outcomes included intubation, deterioration, and hospitalization. Random-effects weighted models were used to pool the specific effect sizes. Subgroup analyses were conducted by stratifying the meta-analysis by region, diabetic status, the adoption of multivariate model, age, risk of bias, and timing for adding metformin. We identified 28 studies with 2,910,462 participants. Meta-analysis of 19 studies showed that metformin is associated with 34% lower COVID-19 mortality [odds ratio (OR), 0.66; 95% confidence interval (CI), 0.56-0.78; = 67.9%] and 27% lower hospitalization rate (pooled OR, 0.73; 95% CI, 0.53-1.00; = 16.8%). However, we did not identify any subgroup effects. The meta-analysis did not identify statistically significant association between metformin and intubation and deterioration of COVID-19 (OR, 0.94; 95% CI, 0.77-1.16; = 0.0% for intubation and OR, 2.04; 95% CI, 0.65-6.34; = 79.4% for deterioration of COVID-19), respectively. Metformin use among COVID-19 patients was associated with a reduced risk of mortality and hospitalization. Our findings suggest a relative benefit for metformin use in nursing home and hospitalized COVID-19 patients. However, randomized controlled trials are warranted to confirm the association between metformin use and COVID-19 outcomes. The study was registered on the PROSPERO on Feb 23, 2021 (CRD42021238722).
PubMed: 34490296
DOI: 10.3389/fmed.2021.704666 -
Medicine Dec 2023Metformin is an old drug used for the treatment of type 2 diabetes mellitus and can play a variety of roles by regulating the gut microbiota. The number of research...
BACKGROUND
Metformin is an old drug used for the treatment of type 2 diabetes mellitus and can play a variety of roles by regulating the gut microbiota. The number of research articles on metformin in the gut microbiota has increased annually; however, no bibliometric tools have been used to analyze the research status and hot trends in this field. This study presents a bibliometric analysis of publications on metformin and gut microbiota.
METHODS
We searched the Web of Science core collection database on June 8, 2023, for papers related to metformin and gut microbiota from 2012 to 2022. We used Microsoft Excel 2021, VOSviewer1.6.19, CiteSpace 6.2.4, and R software package "bibliometrix" 4.0.0 to analyze the countries, institutions, authors, journals, citations, and keywords of the included publications.
RESULTS
We included 517 papers, and the trend in publications increased over the last 11 years. The 517 articles were from 57 countries, including 991 institutions and 3316 authors, and were published in 259 journals. China led all countries (233 papers) and the most influential institution was the Chinese Academy of Sciences (16 papers). PLOS ONE (19 papers) was the most popular journal, and Nature (1598 citations) was the most cited journal. Li and Kim were the 2 most published authors (six papers each), and Cani (272 co-citations) was the most co-cited author. "Metabolites," "aging," and "intestinal barrier" were emerging topics in this field.
CONCLUSIONS
This bibliometric study comprehensively summarizes the research trends and progress of metformin and gut microbiota, and provides new research topics and trends for studying the effects of metformin on gut microbiota in different diseases.
Topics: Humans; Metformin; Gastrointestinal Microbiome; Diabetes Mellitus, Type 2; Academies and Institutes; Bibliometrics
PubMed: 38115325
DOI: 10.1097/MD.0000000000036478 -
International Journal of Epidemiology Apr 2017Existing observational studies provide conflicting evidence for the causal effect of metformin use on cancer risk in patients with type-2 diabetes, and there are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Existing observational studies provide conflicting evidence for the causal effect of metformin use on cancer risk in patients with type-2 diabetes, and there are concerns about bias affecting a number of studies.
METHODS
MEDLINE was used to identify observational studies investigating the association between metformin and overall or site-specific cancer in people with type-2 diabetes. A systematic data extraction and bias assessment was conducted, in which risk of eight bias domains (outcome, exposure, control selection, baseline confounding, time-dependent confounding, immortal time, missing data, censoring methods) were assessed against pre-defined criteria, and rated as unlikely, low, medium or high.
RESULTS
Of 46 studies identified, 21 assessed the effect of metformin on all cancer. Reported relative risks ranged from 0.23 to 1.22, with 12/21 reporting a statistically significant protective effect and none a harmful effect. The range of estimates was similar for site-specific cancers; 3/46 studies were rated as low or unlikely risk of bias in all domains. Two of these had results consistent with no effect of metformin; one observed a moderate protective effect overall, but presented further analyses that the authors concluded were inconsistent with causality. However, 28/46 studies were at risk from bias through exposure definition, 22 through insufficient baseline adjustment and 35 from possible time-dependent confounding.
CONCLUSIONS
Observational studies on metformin and cancer varied in design, and the majority were at risk of a range of biases. The studies least likely to be affected by bias did not support a causal effect of metformin on cancer risk.
Topics: Bias; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Neoplasms; Observational Studies as Topic
PubMed: 28031313
DOI: 10.1093/ije/dyw275 -
Cureus Jul 2023Polycystic ovarian syndrome (PCOS) is a widespread, complex, and multi-system hormonal disorder that occurs in women of reproductive age. The wide variation in practice... (Review)
Review
Polycystic ovarian syndrome (PCOS) is a widespread, complex, and multi-system hormonal disorder that occurs in women of reproductive age. The wide variation in practice in the treatment of PCOS is a direct consequence of the lack of sufficient evidence on alternative treatment strategies, as well as a poor understanding of the disorder itself. The aim of our systematic review was to assess the therapeutic advantages and adverse effects of metformin (MET), a standard treatment modality, with myoinositol (MI), a recent substitute that may be used alone or in combination with other remedies to treat PCOS. A literature search was done using PubMed Central, PubMed, Medline, Cochrane, Science Direct, and Google Scholar. Studies were limited to those published in English between 2012 and 2022 that focused on the management of PCOS with both MET and MI. The systematic review complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Using standard quality assessment tools, two reviewers independently assessed the content of the incorporated studies. Three meta-analyses, eight randomized controlled trials (RCTs), and one non-randomized non-controlled trial (NN-RCT) were deemed eligible. Following extensive analysis, we found that MET and MI are comparable in their effects on clinical, hormonal, and biochemical profiles. MI, however, had a better safety profile and tolerance due to minimal side effects compared to MET. These results demonstrate the potential role of MI as a novel asset in the armamentarium in the management of PCOS.
PubMed: 37575860
DOI: 10.7759/cureus.41748 -
PloS One 2016Although clozapine is the gold-standard for treatment refractory schizophrenia, it has the worst metabolic profile of all antipsychotics. This is partly mediated by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although clozapine is the gold-standard for treatment refractory schizophrenia, it has the worst metabolic profile of all antipsychotics. This is partly mediated by clozapine's impact on glucagon-like peptide (GLP-1). There is an absence of robust evidence for effective treatments for clozapine associated weight gain and metabolic syndrome. Metformin, with its role in increasing GLP-1 may aid weight loss among people on clozapine.
METHODS
We conducted a systematic-review and meta-analysis of metformin versus placebo for change in weight and metabolic syndrome for people on clozapine without diabetes mellitus. We searched the Cochrane Schizophrenia Group's trial register, Pubmed and Embase, as well as the following Chinese databases: the Chinese Biomedical Literature Service System and China Knowledge Resource Integrated Database. This was supplemented by hand searches of key papers.
RESULTS
Eight studies, of which three were from Chinese databases, with 478 participants were included. We found that metformin was superior to placebo in terms of weight loss (-3.12kg, 95%CI -4.88kg to -1.37kg) and BMI (-1.18kg/m2, 95%CI -1.76kg/m2 to -0.61kg/m2). Metformin significantly improved three of the five components of metabolic syndrome; waist circumference, fasting glucose and triglycerides. Sensitivity analysis on study quality and duration did not greatly impact results.
CONCLUSIONS
Metformin led to clinically meaningful weight loss among people on clozapine, and may reduce the rates of metabolic syndrome. Inclusion of metformin into the treatment protocols of people on clozapine, as tolerated, should be considered.
TRIAL REGISTRATION
PROSPERO registration number: CRD42015029723.
Topics: Antipsychotic Agents; Blood Glucose; Body Mass Index; Body Weight; Clozapine; Fasting; Humans; Hypoglycemic Agents; Metabolic Syndrome; Metformin; Obesity; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome; Triglycerides; Waist Circumference; Weight Gain
PubMed: 27304831
DOI: 10.1371/journal.pone.0156208 -
World Journal of Hepatology Jun 2015Metformin, a biguanide derivative, is the most commonly prescribed medication in the treatment of type 2 diabetes mellitus. More recently, the use of metformin has shown... (Review)
Review
Metformin, a biguanide derivative, is the most commonly prescribed medication in the treatment of type 2 diabetes mellitus. More recently, the use of metformin has shown potential as a preventive and therapeutic agent for a broad spectrum of conditions, including liver disease and hepatic malignancies. In this systematic review, we critically analyze the literature behind the potential use of metformin across the spectrum of liver disease and malignancies. The PubMed and Ovid MEDLINE databases were searched from 2000 to March 2015, using a combination of relevant text words and MeSH terms: metformin and mammalian target of rapamycin, hepatitis B virus (HBV), hepatitis B virus (HCV), non-alcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC) or cholangiocarcinoma. The search results were evaluated for pertinence to the issue of metformin in liver disease as well as for quality of study design. Metformin has a number of biochemical effects that would suggest a benefit in treating chronic liver diseases, particularly in the context of insulin resistance and inflammation. However, the literature thus far does not support any independent therapeutic role in NAFLD or HCV. Nonetheless, there is Level III evidence for a chemopreventive role in patients with diabetes and chronic liver disease, with decreased incidence of HCC and cholangiocarcinoma. The use of metformin seems to be safe in patients with cirrhosis, and provides a survival benefit. Once hepatic malignancies are already established, metformin does not offer any therapeutic potential. In conclusion, there is insufficient evidence to recommend use of metformin in the adjunctive treatment of chronic liver diseases, including NAFLD and HCV. However, there is good evidence for a chemopreventive role against HCC among patients with diabetes and chronic liver disease, and metformin should be continued in patients even with cirrhosis to provide this benefit.
PubMed: 26140084
DOI: 10.4254/wjh.v7.i12.1652 -
American Journal of Cardiovascular... Jan 2024Pulmonary arterial hypertension (PAH) is a progressive, cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pulmonary arterial hypertension (PAH) is a progressive, cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent ventricular dilatation and failure. New therapeutic targets are being investigated for their potential roles in improving PAH patients' symptoms and reversing pulmonary vascular pathology.
METHOD
We aimed to address the available knowledge from the published randomized controlled trials (RCTs) regarding the role of Rho-kinase (ROCK) inhibitors, bone morphogenetic protein 2 (BMP2) inhibitors, estrogen inhibitors, and AMP-activated protein kinase (AMPK) activators on the PAH evaluation parameters. This systematic review (SR) was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CDR42022340658) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Overall, 5092 records were screened from different database and registries; 8 RCTs that met our inclusion criteria were included. The marked difference in the study designs and the variability of the selected outcome measurement tools among the studies made performing a meta-analysis impossible. However, the main findings of this SR relate to the powerful potential of the AMPK activator and the imminent antidiabetic drug metformin, and the BMP2 inhibitor sotatercept as promising PAH-modifying therapies. There is a need for long-term studies to evaluate the effect of the ROCK inhibitor fasudil and the estrogen aromatase inhibitor anastrozole in PAH patients. The role of tacrolimus in PAH is questionable. The discrepancy in the hemodynamic and clinical parameters necessitates defining cut values to predict improvement. The differences in the PAH etiologies render the judgment of the therapeutic potential of the tested drugs challenging.
CONCLUSION
Metformin and sotatercept appear as promising therapeutic drugs for PAH.
CLINICAL TRIALS REGISTRATION
This work was registered in PROSPERO (CDR42022340658).
Topics: Humans; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; AMP-Activated Protein Kinases; Familial Primary Pulmonary Hypertension; Estrogens; Metformin
PubMed: 37945977
DOI: 10.1007/s40256-023-00613-5 -
BJUI Compass Jan 2023Metformin, the first line pharmacotherapy for type 2 diabetes has demonstrated favourable effects in prostate cancer (PCa) across a range of studies evaluating PCa... (Review)
Review
Metformin, the first line pharmacotherapy for type 2 diabetes has demonstrated favourable effects in prostate cancer (PCa) across a range of studies evaluating PCa patient outcomes amongst metformin users. However, a lack of rigorously conducted prospective studies has stalled clinical use in this setting. Despite multiple studies evaluating the mechanisms underpinning antitumour effects of metformin in PCa, to date, no reviews have compared these findings. This systematic review and meta-analysis consolidates the mechanisms accounting for the antitumour effect of metformin in PCa and evaluates the antitumour efficacy of metformin in preclinical PCa studies. Data were obtained through Medline and EMBASE, extracted by two independent assessors. Risk of bias was assessed using the TOXR tool. Meta-analysis compared in vivo reductions of PCa tumour volume with metformin. In total, 447 articles were identified with 80 duplicates, and 261 articles excluded based on eligibility criteria. The remaining 106 articles were assessed and 71 excluded, with 35 articles included for systematic review, and eight included for meta-analysis. The mechanisms of action of metformin regarding tumour growth, viability, migration, invasion, cell metabolism, and activation of signalling cascades are individually discussed. The mechanisms by which metformin inhibits PCa cell growth are multimodal. Metformin regulates expression of multiple proteins/genes to inhibit cellular proliferation, cell cycle progression, and cellular invasion and migration. Published in vivo studies also conclusively demonstrate that metformin inhibits PCa growth. This highlights the potential of metformin to be repurposed as an anticancer agent, warranting further investigation of metformin in the setting of PCa.
PubMed: 36569495
DOI: 10.1002/bco2.187