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Frontiers in Pharmacology 2023Metformin has recently been demonstrated to have an anti-melanogenic activity. Nevertheless, clinical evidence of the effectiveness of metformin in melasma is lacking....
Metformin has recently been demonstrated to have an anti-melanogenic activity. Nevertheless, clinical evidence of the effectiveness of metformin in melasma is lacking. The objective of this study was to assess the efficacy and safety of metformin in the treatment of melasma. MEDLINE, Embase, PubMed, Cochrane Library (CENTRAL), Scopus, CINAHL, and grey literature databases were searched to 4 October 2022 and updated on 26 February 2023. Randomized controlled trials (RCTs), quasi-RCTs, observational studies, case series, and case reports investigating the efficacy and safety of metformin for melasma were included. The Melasma Area Severity Index (MASI) scores that changed from baseline were pooled using fixed-effects model and expressed as standardized mean differences (SMDs) and 95% confidence intervals (CIs). Three RCTs including 140 patients with melasma were included. The results demonstrated that after 8 weeks, 15% topical metformin significantly reduced the Melasma Area Severity Index (MASI) score compared to placebo (1 trial; = 60; MD, -0.56; 95% CI, -1.07 to -0.04; = 0.034). Furthermore, when compared to triple combination cream (TCC), 30% topical metformin demonstrated similar efficacy in reducing the MASI score after 8 weeks (2 trials; = 80; MD, 0.19, 95% CI, -0.25 to 0.63; = 0.390). Patients using 30% topical metformin had fewer adverse events compared to TCC users, although no statistical difference was found. Topical metformin was as effective as triple combination cream (TCC) in decreasing changes in the MASI score in patients with melasma, with minimum adverse events. Further studies with larger sample sizes, longer follow-up times, and well-designed trials are required. Identifier PROSPERO (CRD42022351966).
PubMed: 38192412
DOI: 10.3389/fphar.2023.1281050 -
Frontiers in Immunology 2023Cancer is a major global health concern, and immune checkpoint inhibitors (ICIs) offer a promising treatment option for cancer patients. However, the efficacy of ICIs...
INTRODUCTION
Cancer is a major global health concern, and immune checkpoint inhibitors (ICIs) offer a promising treatment option for cancer patients. However, the efficacy of ICIs can be influenced by various factors, including the use of concomitant medications.
METHODS
We searched databases (PubMed, Embase, Cochrane Library, Web of Science) for systematic reviews and meta-analyses for systematic reviews and meta-analyses on the impact of concomitant medications on ICIs efficacy, published from inception to January 1, 2023. We evaluated the methodological quality of the included meta-analyses, and re-synthesized data using a random-effects model and evidence stratification.
RESULTS
We included 23 publications, comprising 11 concomitant medications and 112 associations. Class II-IV evidence suggested that antibiotics have a negative impact on ICIs efficacy. However, ICIs efficacy against melanoma, hepatocellular carcinoma, and esophageal squamous cell carcinoma was not affected, this effect was related to the exposure window (class IV). Class III evidence suggested that proton pump inhibitors have a negative impact on ICIs efficacy; nevertheless, the efficacy against melanoma and renal cell carcinoma was not affected, and the effect was related to exposure before the initiation of ICIs therapy (class II). Although class II/III evidence suggested that steroids have a negative impact, this effect was not observed when used for non-cancer indications and immune-related adverse events (class IV). Class IV evidence suggested that opioids reduce ICIs efficacy, whereas statins and probiotics may improve ICIs efficacy. ICIs efficacy was not affected by histamine 2 receptor antagonists, aspirin, metformin, β-blockers, and nonsteroidal anti-inflammatory agents.
CONCLUSION
Current evidence suggests that the use of antibiotics, PPIs, steroids, and opioids has a negative impact on the efficacy of ICIs. However, this effect may vary depending on the type of tumor, the timing of exposure, and the intended application. Weak evidence suggests that statins and probiotics may enhance the efficacy of ICIs. Aspirin, metformin, β-blockers, and NSAIDs do not appear to affect the efficacy of ICIs. However, caution is advised in interpreting these results due to methodological limitations.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO,identifier, CRD42022328681.
Topics: Humans; Analgesics, Opioid; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Esophageal Neoplasms; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immune Checkpoint Inhibitors; Kidney Neoplasms; Liver Neoplasms; Melanoma; Metformin; Steroids; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 37841249
DOI: 10.3389/fimmu.2023.1218386 -
Medicina (Kaunas, Lithuania) May 2023Studies have shown that people with diabetes have a high risk of osteoporosis and fractures. The effect of diabetic medications on bone disease cannot be ignored. This... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Studies have shown that people with diabetes have a high risk of osteoporosis and fractures. The effect of diabetic medications on bone disease cannot be ignored. This meta-analysis aimed to compare the effects of two types of glucose-lowering drugs, metformin and thiazolidinediones (TZD), on bone mineral density and bone metabolism in patients with diabetes mellitus.
METHODS
This systematic review and meta-analysis were prospectively registered on PROSPERO, and the registration number is CRD42022320884. Embase, PubMed, and Cochrane Library databases were searched to identify clinical trials comparing the effects of metformin and thiazolidinediones on bone metabolism in patients with diabetes. The literature was screened by inclusion and exclusion criteria. Two assessors independently assessed the quality of the identified studies and extracted relevant data.
RESULTS
Seven studies involving 1656 patients were finally included. Our results showed that the metformin group had a 2.77% (SMD = 2.77, 95%CI [2.11, 3.43]; < 0.00001) higher bone mineral density (BMD) than the thiazolidinedione group until 52 weeks; however, between 52 and 76 weeks, the metformin group had a 0.83% (SMD = -0.83, 95%CI: [-3.56, -0.45]; = 0.01) lower BMD. The C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-terminal propeptide (PINP) were decreased by 18.46% (MD = -18.46, 95%CI: [-27.98, -8.94], = 0.0001) and 9.94% (MD = -9.94, 95%CI: [-16.92, -2.96], = 0.005) in the metformin group compared with the TZD group.
Topics: Humans; Metformin; Osteoporosis; Diabetes Mellitus, Type 2; Bone Density; Thiazolidinediones
PubMed: 37241136
DOI: 10.3390/medicina59050904 -
American Journal of Obstetrics and... Mar 2024This study aimed to examine the impact of maternal metformin use during pregnancy on offspring neurodevelopmental outcomes. (Review)
Review
OBJECTIVE
This study aimed to examine the impact of maternal metformin use during pregnancy on offspring neurodevelopmental outcomes.
DATA SOURCES
MEDLINE, Embase, and Web of Science (Core Collection) were searched from inception until July 1, 2023.
STUDY ELIGIBILITY CRITERIA
Studies of women who received treatment with metformin at any stage of pregnancy for any indication with neurodevelopmental data available for their offspring were included. Studies without a control group were excluded. Randomized controlled trials, case-control, cohort, and cross-sectional studies were included in the review.
METHODS
Studies were screened for inclusion and data were extracted independently by 2 reviewers. Risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale for nonrandomized studies, and the Risk of Bias 2 tool for randomized trials.
RESULTS
A total of 7 studies met the inclusion criteria, including a combined cohort of 14,042 children with 7641 children who were exposed and followed for up to 14 years of age. Metformin use during pregnancy was not associated with neurodevelopmental delay in infancy (relative risk, 1.09; 95% confidence interval, 0.54-2.17; 3 studies; 9668 children) or at ages 3 to 5 years (relative risk, 0.90; 95% confidence interval, 0.56-1.45; 2 studies; 6118 children). When compared with unexposed peers, metformin use during pregnancy was not associated with altered motor scores (mean difference, 0.30; 95% confidence interval, -1.15 to 1.74; 3 studies; 714 children) or cognitive scores (mean difference, -0.45; 95% confidence interval, -1.45 to 0.55; 4 studies; 734 children). Studies that were included were of high quality and deemed to be at low risk of bias.
CONCLUSION
In utero exposure to metformin does not seem to be associated with adverse neurodevelopmental outcomes in children up to the age of 14 years. These findings provide reassurance to clinicians and pregnant women considering metformin use during pregnancy.
PubMed: 38460832
DOI: 10.1016/j.ajog.2024.02.316 -
World Journal of Gastroenterology Feb 2024Most patients with advanced pancreatic neuroendocrine tumors (pNETs) die due to tumor progression. Therefore, identifying new therapies with low toxicity and good... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Most patients with advanced pancreatic neuroendocrine tumors (pNETs) die due to tumor progression. Therefore, identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant. In this perspective, metformin is emerging as a molecule of interest. Retrospective studies have described metformin, a widely used agent for the treatment of patients with type 2 diabetes mellitus (T2DM), to be effective in modulating different tumor-related events, including cancer incidence, recurrence and survival by inhibiting mTOR phosphorylation. This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.
AIM
To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and post-treatment outcomes of pNET.
METHODS
A systematic review of the published literature was undertaken, focusing on the role of T2DM and metformin in insurgence and prognosis of pNET, measured through outcomes of tumor-free survival (TFS), overall survival and progression-free survival.
RESULTS
A total of 13 studies (5674 patients) were included in this review. Analysis of 809 pNET cases from five retrospective studies (low study heterogeneity with = 0%) confirms the correlation between T2DM and insurgence of pNET (OR = 2.13, 95%CI = 1.56-4.55; < 0.001). The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients (hazard ratio = 1.84, 95%CI = 0.78-2.90; < 0.001). The study heterogeneity was intermediate, with = 51%. A few studies limited the possibility of performing pooled analysis in the setting of metformin; therefore, results were heterogeneous, with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.
CONCLUSION
T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients. Unfortunately, a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Neuroendocrine Tumors; Retrospective Studies; Pancreatic Neoplasms; Neuroectodermal Tumors, Primitive
PubMed: 38515954
DOI: 10.3748/wjg.v30.i7.759 -
Journal of Reproduction & Infertility 2023Cell-free fetal DNA (cffDNA) is a novel screening method for fetal aneuploidy that facilitated non-invasive prenatal testing (NIPT) through analysis of cffDNA in... (Review)
Review
BACKGROUND
Cell-free fetal DNA (cffDNA) is a novel screening method for fetal aneuploidy that facilitated non-invasive prenatal testing (NIPT) through analysis of cffDNA in maternal plasma. However, despite increased sensitivity, it has a number of limitations that may complicate of its results interpretation. Therefore, elucidating factors affecting fetal fraction, as a critical limitation, guides its clinical application.
METHODS
In this report, systematic search was carried out through PubMed, Web of Science, and Scopus databases until February 11, 2022 by using keywords consist of "noninvasive prenatal screening", "NIPT", "noninvasive prenatal", "cell free DNA" and "fetal fraction". The articles were screened for eligibility criteria before data extraction.
RESULTS
A total of 39 eligible studies, most published between 2010 and 2020, were included. Based on the results of studies, a negative correlation between maternal age and BMI/body weight with fetal fraction was found. Furthermore, LDL, cholesterol, triglyceride level, metformin, heparin and enoxaparin therapy, hemoglobin-related hemoglobinopathies, and physical activity showed to have negative associations. Interestingly, it seems the ethnicity of patients from South and East Asia has a correlation with fetal fraction compared to Caucasians. Positive correlation was observed between gestational age, free β-hCG, PAPP-A, living in high altitude, and twin pregnancy.
CONCLUSION
Considering each factor, there was significant inconsistency and controversy regarding their impact on outcomes. Indeed, multiple factors can influence the accuracy of NIPS results, and it is worth noting that the impact of these factors may vary depending on the individual's ethnic background. Therefore, it is important to recognize that NIPS remains a screening test, and comprehensive pre- and post-NIPS counseling should be conducted as part of standard clinical practice.
PubMed: 38164433
DOI: 10.18502/jri.v24i4.14149 -
Cureus Sep 2023Diabetes mellitus is a growing global health concern, and prevention strategies play a crucial role in reducing its burden. Metformin has been widely studied as a... (Review)
Review
Diabetes mellitus is a growing global health concern, and prevention strategies play a crucial role in reducing its burden. Metformin has been widely studied as a potential intervention for diabetes prevention, but its overall effectiveness and impact on various populations remain unclear. This study aims to provide a comprehensive synthesis of the available evidence on the effectiveness of metformin in diabetes prevention. A systematic search was conducted in PubMed, Scopus, ScienceDirect, and Google Scholar for articles published from inception to June 2023. The reference lists of the included studies were also searched to retrieve possible additional studies. Any quantitative data were analyzed using Review Manager 5.4. A -value of 0.05 was adopted as the significance threshold. Our analysis included 17 studies with a total sample size of 30,474. Our meta-analysis included two key analyses. First, the meta-analysis evaluating the effects of metformin on prediabetes demonstrated a significant reduction in the risk of progressing to type 2 diabetes mellitus (T2DM). The pooled odds ratio (OR) was 0.65 (95% confidence interval [CI] 0.53-0.80), indicating a 35% lower odds of developing T2DM among individuals with prediabetes who received metformin interventions compared to control groups. Secondly, the meta-analysis assessing the efficacy of metformin interventions in preventing T2DM yielded a significant reduction in the risk of developing the disease. The pooled risk ratio was 0.58 (95% CI 0.44-0.77), indicating a 42% lower risk of developing T2DM in individuals receiving metformin interventions compared to those in non-metformin intervention groups. These findings provide strong evidence for the effectiveness of metformin in preventing the progression of prediabetes to T2DM and reducing the overall incidence of the disease. The review demonstrated that metformin is effective in reducing the risk of developing diabetes mellitus among individuals at risk for the disease. The findings highlight the potential of metformin as a valuable intervention for diabetes prevention, particularly in high-risk populations.
PubMed: 37900422
DOI: 10.7759/cureus.46108 -
Frontiers in Endocrinology 2023Due to its high heterogenicity and unclear etiology, there is currently no specific treatment for polycystic ovary syndrome (PCOS). Metformin, as an insulin sensitizer,... (Meta-Analysis)
Meta-Analysis
AIMS
Due to its high heterogenicity and unclear etiology, there is currently no specific treatment for polycystic ovary syndrome (PCOS). Metformin, as an insulin sensitizer, combined with spironolactone, an antiandrogen medication, may exert complementary effects on PCOS. We therefore performed a meta-analysis of trials in which metformin combined with spironolactone was applied to treat PCOS to evaluate the efficacy and safety of the combination therapy.
METHODS
We retrieved the PubMed, Embase, Scopus, Cochrane Library, CNKI, CBM, Wangfang, and VIP databases for literatures published from their inception to December 16, 2022 on the effects of metformin combined with spironolactone in the treatment of PCOS. Inclusion criteria according to P.I.C.O.S criteria were: PCOS patients, metformin combined with spironolactone interventions, metformin alone control group, and randomized controlled trials with the following outcome data: body mass index (BMI), hirsutism score, luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), fasting blood glucose (FBG), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and side effects including nausea, vomiting, diarrhea and drug withdrawal.
RESULTS
Our results revealed that metformin combined with spironolactone significantly reduced BMI and TT, but that it exerted no significant effects on hirsutism score, or on FSH or LH concentrations. Combined treatment also resulted in a significant diminution in FBG and insulin resistance using the HOMA-IR when the interventional time was greater than 6 months. In addition, the combination did not have a higher occurrence of adverse reactions than metformin alone.
CONCLUSION
Compared with metformin alone, metformin combined with spironolactone therapy may be more effective in reducing BMI and serum androgen levels, but the combination showed no significant effect on the hirsutism score or gonadotropin hormone levels, and was not associated with an elevation in side-effects. Moreover, when the treatment course was greater than 6 months, combination therapy reduced FBG and improved insulin resistance more effectively than metformin alone. However, more research is needed to determine the most effective course of treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022355515.
Topics: Female; Humans; Hirsutism; Insulin Resistance; Polycystic Ovary Syndrome; Spironolactone; Drug-Related Side Effects and Adverse Reactions; Follicle Stimulating Hormone, Human; Luteinizing Hormone
PubMed: 37635987
DOI: 10.3389/fendo.2023.1223768 -
Cancers May 2023Quality pharmacological treatment can improve survival in many types of cancer. Drug repurposing offers advantages in comparison with traditional drug development... (Review)
Review
Quality pharmacological treatment can improve survival in many types of cancer. Drug repurposing offers advantages in comparison with traditional drug development procedures, reducing time and risk. This systematic review identified the most recent randomized controlled clinical trials that focus on drug repurposing in oncology. We found that only a few clinical trials were placebo-controlled or standard-of-care-alone-controlled. Metformin has been studied for potential use in various types of cancer, including prostate, lung, and pancreatic cancer. Other studies assessed the possible use of the antiparasitic agent mebendazole in colorectal cancer and of propranolol in multiple myeloma or, when combined with etodolac, in breast cancer. We were able to identify trials that study the potential use of known antineoplastics in other non-oncological conditions, such as imatinib for severe coronavirus disease in 2019 or a study protocol aiming to assess the possible repurposing of leuprolide for Alzheimer's disease. Major limitations of these clinical trials were the small sample size, the high clinical heterogeneity of the participants regarding the stage of the neoplastic disease, and the lack of accounting for multimorbidity and other baseline clinical characteristics. Drug repurposing possibilities in oncology must be carefully examined with well-designed trials, considering factors that could influence prognosis.
PubMed: 37296934
DOI: 10.3390/cancers15112972 -
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