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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 -
World Journal of Surgical Oncology Jul 2023To summarize the chemo-radio effect of metformin in rectal cancers with neoadjuvant chemoradiotherapy on pathological response, tumor regression grade (TRG), and T/N... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To summarize the chemo-radio effect of metformin in rectal cancers with neoadjuvant chemoradiotherapy on pathological response, tumor regression grade (TRG), and T/N downstaging.
METHODS
PubMed, MEDLINE, Embase, and Cochrane Database of collected reviews were searched up to June 30, 2022. This study conducted systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) sheet. Odds ratios (ORs) and confidence intervals (CIs) which calculated by random-effects models were displayed in forest plots. Newcastle-Ottawa scale was used to assess the risk of bias of the observational cohort studies.
RESULTS
This systematic review and meta-analysis comprised eight cohorts out of seven studies, with 2294 patients in total. We performed two-way comparison for metformin in diabetic patients vs (1) non-metformin drugs in diabetic patients and (2) nondiabetic patients. In diabetes patient studies, the metformin group had a significantly increased pathological response on TRG (OR: 3.28, CI: 2.01-5.35, I = 0%, p < 0.001) and T downstaging (OR: 2.14, CI: 1.24-3.67, I = 14%, p = 0.006) in comparison with a non-metformin group. When compared with nondiabetic patients, the pathological response on TRG (OR: 2.67, CI: 1.65-4.32, I = 43%, p < 0.001) and T downstaging (OR: 1.96, CI: 1.04-3.71, I = 66%, p = 0.04) were also higher in metformin group. The limitation was that no randomized controlled trials were available based on current literature review. Small sample sizes for diabetic metformin or non-metformin users in rectal cancer patients reduced the power of the study.
CONCLUSIONS
For patients with rectal cancer and treated with neoadjuvant chemoradiotherapy, metformin administration in diabetic patients increased the pathological response on tumor-regression grade and T downstaging. Further well-designed, high-quality randomized controlled trials are required to reveal the actual effect of metformin.
Topics: Humans; Metformin; Neoadjuvant Therapy; Chemoradiotherapy; Rectal Neoplasms; Diabetes Mellitus; Treatment Outcome
PubMed: 37491250
DOI: 10.1186/s12957-023-03087-6 -
European Journal of Endocrinology Aug 2023Available evidence has shown that metformin improves insulin sensitivity and weight management in polycystic ovary syndrome (PCOS). Nevertheless, key knowledge gaps... (Meta-Analysis)
Meta-Analysis
The impact of metformin with or without lifestyle modification versus placebo on polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
Available evidence has shown that metformin improves insulin sensitivity and weight management in polycystic ovary syndrome (PCOS). Nevertheless, key knowledge gaps remain regarding its efficacy and the specific outcomes in this population. This review evaluates the effectiveness of metformin and lifestyle modification compared with placebo in the management of PCOS and will inform the forthcoming, 2023 evidence-based PCOS guidelines.
DESIGN
Systematic review and meta-analysis of the literature.
METHODS
A search was performed in MEDLINE, EMBASE, PsycINFO, All EBM, and CINAHL. The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and included randomized controlled trials published in English through July 2022.
RESULTS
Moderate certainty of evidence showed a larger reduction of body mass index (BMI) (mean difference [MD] -0.53, 95% confidence interval [CI] -0.95 to -0.12 kg/m2), homeostatic model assessment for insulin resistance (MD -0.50, 95% CI -0.91 to -0.09) (critical outcomes), and fasting glucose (MD -0.13, 95% CI -0.19 to -0.07 mmol/L) with metformin compared to placebo with increased mild gastrointestinal adverse effects (odds ratio [OR] 7.67, 95% CI 2.74-21.46). Low certainty of evidence showed a larger reduction of waist-hip ratio (MD -0.02, 95% CI -0.03 to -0.00), total cholesterol (MD -0.24, 95% CI -0.43 to -0.05 mmol/L), low-density lipoprotein (MD -0.16, 95% CI -0.30 to -0.01 mmol/L), and triglycerides (MD -0.11, 95% CI -0.20 to -0.02 mmol/L) with metformin than placebo.
CONCLUSIONS
Metformin should be considered an efficacious adjunct to lifestyle interventions in adults with PCOS, especially for those with a higher BMI, to improve weight loss, insulin resistance, and lipids.
Topics: Adult; Female; Humans; Metformin; Polycystic Ovary Syndrome; Insulin Resistance; Randomized Controlled Trials as Topic; Life Style; Hypoglycemic Agents
PubMed: 37536294
DOI: 10.1093/ejendo/lvad098 -
Frontiers in Psychiatry 2023Metformin has shown good efficacy in the management of antipsychotic-induced metabolic syndrome (MetS) in patients with schizophrenia or schizoaffective disorders. Its... (Review)
Review
The potential effect of metformin on cognitive and other symptom dimensions in patients with schizophrenia and antipsychotic-induced weight gain: a systematic review, meta-analysis, and meta-regression.
INTRODUCTION
Metformin has shown good efficacy in the management of antipsychotic-induced metabolic syndrome (MetS) in patients with schizophrenia or schizoaffective disorders. Its ability to induce antidepressant behavioural effects and improve cognitive functions has also been investigated: yet information has not been systematized. The aim of this study was therefore to investigate the effects of metformin on cognitive and other symptom dimension in schizophrenic patients treated with antipsychotics through a systematic review and meta-analysis.
METHODS
We searched PubMed, ClinicalTrials.Gov, Embase, PsycINFO, and WHO ICTRP database up to February 2022, Randomised Controlled Trials (RCT) evaluating patients diagnosed with schizophrenia and related disorders, who were treated with metformin as add-on therapy to antipsychotics for the treatment of weight gain and in which changes in psychiatric symptoms and cognitive functions were evaluated.
RESULTS
A total of 19 RCTs met the inclusion criteria. Meta-analysis was performed on 12 eligible studies. We found a positive trend after 24 weeks of treatment in schizophrenic patients with stable conditions [SMD (95%CI) = -0.40 (-0.82;0.01), OR (95%CI) = 0.5 (-2.4;3.4)]. Better performance was detected in the Brief Assessment of Cognition in Schizophrenia and Positive and Negative Syndrome Scale (PANSS) with low heterogeneity among studies. One study reported changes in BACS-verbal memory subdomain in favour of placebo [MD (95%CI) = -16.03 (-23.65;8.42)]. Gastrointestinal disorders, xerostomia, and extrapyramidal syndrome were the most reported adverse effects. Psychiatric adverse events were also described: in particular, symptoms attributable to a relapse of schizophrenia.
CONCLUSION
Some degree of efficacy was found for Metformin in improving cognitive and other symptom dimensions in patients with Schizophrenia. Given the clinical relevance of this potential pharmacological effect, longer specific studies using adequate psychometric scales are strongly recommended. Likewise, how metformin acts in this context needs to be evaluated in order to enhance its efficacy or find more efficacious drugs.
PubMed: 37502816
DOI: 10.3389/fpsyt.2023.1215807 -
The Journal of Maternal-fetal &... Dec 2024The use of metformin for treating gestational diabetes mellitus (GDM) remains controversial because it can pass through the placenta. This meta-analysis aimed to compare... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The use of metformin for treating gestational diabetes mellitus (GDM) remains controversial because it can pass through the placenta. This meta-analysis aimed to compare the effects of metformin and insulin on maternal and neonatal outcomes in patients with GDM.
METHODS
We conducted a comprehensive search of the PubMed, Embase, and Cochrane Library databases, focusing on randomized controlled trials (RCTs) that evaluated the impacts of metformin and insulin on both maternal and neonatal outcomes in patients with GDM.
RESULTS
Twenty-four RCTs involving 4934 patients with GDM were included in this meta-analysis. Compared with insulin, metformin demonstrated a significant reduction in the risks of preeclampsia (RR 0.61, 95% CI 0.48 to 0.78, < .0001), induction of labor (RR 0.90, 95% CI 0.82 to 0.98, = .02), cesarean delivery (RR 0.91, 95% CI 0.85 to 0.98, = .01), macrosomia (RR 0.67, 95% CI 0.53 to 0.83, = .0004), neonatal intensive care unit (NICU) admission (RR 0.75, 95% CI 0.66 to 0.86, < .0001), neonatal hypoglycemia (RR 0.55, 95% CI 0.48 to 0.63, < .00001), and large for gestational age (LGA) (RR 0.80, 95% CI 0.68 to 0.94, = .007). Conversely, metformin showed no significant impact on gestational hypertension (RR 0.84, 95% CI 0.67 to 1.06, = .15), spontaneous vaginal delivery (RR 1.13, 95% CI 1.00 to 1.08, = .05), emergency cesarean section (RR 0.94, 95% CI 0.77 to 1.16, = .58), shoulder dystocia (RR 0.65, 95% CI 0.31 to 1.39, = .27), premature birth (RR 0. 92, 95% CI 0.61 to 1.39, = .69), polyhydramnios (RR 1.11, 95% CI 0.54 to 2.30, = .77), birth trauma (RR 0.87, 95% CI 0.54 to 1.39, = .56), 5-min Apgar score < 7 (RR 1.13, 95% CI 0.76 to 1.68, = .55), small for gestational age (SGA) (RR 0.93, 95% CI 0.71 to 1.22, = .62), respiratory distress syndrome (RDS) (RR 0.74, 95% CI 0.50 to 1.08, = .11), jaundice (RR 1.09, 95% CI 0.95 to 1.25, = .24) or birth defects (RR 0.80, 95% CI 0.37 to 1.74, = .57).
CONCLUSIONS
The findings suggest that metformin can reduce the risk of certain maternal and neonatal outcomes compared with insulin therapy for GDM. However, long-term follow-up studies of patients with GDM taking metformin and their offspring are warranted to provide further evidence.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Diabetes, Gestational; Fetal Macrosomia; Hypoglycemia; Insulin; Metformin; Weight Gain
PubMed: 38124287
DOI: 10.1080/14767058.2023.2295809 -
European Journal of Medical Research Sep 2023It has been reported that metformin use may reduce the risk of thyroid cancer, but existing studies have generated inconsistent results. The purpose of this study was to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It has been reported that metformin use may reduce the risk of thyroid cancer, but existing studies have generated inconsistent results. The purpose of this study was to investigate such association between metformin use and the risk of thyroid cancer.
METHODS
Studies of metformin use for the risk of thyroid cancer were searched in Web of Science, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biomedical Database, Wanfang Data, and Chinese Scientific Journals Database (VIP) from the establishment date to December 2022. Newcastle-Ottawa scale is adopted for assessing the methodological quality of included studies, and the inter-study heterogeneity was assessed by using the I-squared statistic. Combined odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated through either fixed-effects or random-effects model according to the heterogeneity. Besides, subgroup analyses, sensitivity analyses and test for publication bias were conducted.
RESULTS
Five studies involving 1,713,528 participants were enrolled in the qualitative and quantitative synthesis. The result of the meta-analyses showed that metformin use was associated with a statistically significant lower risk of thyroid cancer (pooled OR = 0.68, 95% CI = 0.50-0.91, P = 0.011). Moreover, in the subgroup analysis, we found that the use of metformin may also aid in the prevention of thyroid cancer in Eastern population (pooled OR = 0.55, 95% CI = 0.35-0.88, P = 0.012) rather than Western population (pooled OR = 0.89, 95% CI = 0.52-1.54, P = 0.685). Sensitivity analysis suggested the results of this meta-analyses were relatively stable. No publication bias was detected.
CONCLUSION
Metformin use is beneficial for reducing the risk of thyroid cancer. For further investigation, more well-designed studies are still needed to elucidate the association between metformin use and the risk of thyroid cancer.
Topics: Humans; Metformin; Risk; Thyroid Neoplasms; China
PubMed: 37773165
DOI: 10.1186/s40001-023-01287-0 -
Frontiers in Pharmacology 2023Hypoglycemic agents are the primary therapeutic approach for the treatment of diabetes and have been postulated to impact pancreatic cancer (PC) incidence in diabetic...
Hypoglycemic agents are the primary therapeutic approach for the treatment of diabetes and have been postulated to impact pancreatic cancer (PC) incidence in diabetic patients. We conducted a meta-analysis to further evaluate and establish the associations between four common types of hypoglycemic agents [metformin, sulfonylureas, thiazolidinediones (TZDs), and insulin] and PC incidence in individuals with diabetes mellitus (DM). A comprehensive literature search of PubMed, Web of Science, Embase, and the Cochrane Library identified studies that analyzed the relationship between hypoglycemic agents and PC published between January 2012 and September 2022. Randomized control trials (RCTs), cohorts, and case-control studies were included if there was clear and evaluated defined exposure to the involved hypoglycemic agents and reported PC outcomes in patients with DM. Furthermore, reported relative risks or odds ratios (ORs) or other provided data were required for the calculation of odds ratios. Summary odds ratio estimates with a 95% confidence interval (CI) were estimated using the random-effects model. Additionally, subgroup analysis was performed to figure out the source of heterogeneity. Sensitivity analysis and publication bias detection were also performed. A total of 11 studies were identified that evaluated one or more of the hypoglycemic agents, including three case-control studies and eight cohort studies. Among these, nine focused on metformin, six on sulfonylureas, seven on TZDs, and seven on insulin. Meta-analysis of the 11 observational studies reported no significant association between metformin (OR = 1.04, 95% CI 0.73-1.46) or TZDs (OR = 1.13, 95% CI 0.73-1.75) and PC incidence, while the risk of PC increased by 79% and 185% with sulfonylureas (OR = 1.79, 95% CI 1.29-2.49) and insulin (OR = 2.85, 95% CI 1.75-4.64), respectively. Considerable heterogeneity was observed among the studies and could not be fully accounted for by study design, region, or adjustment for other hypoglycemic agents. Sulfonylureas and insulin may increase the incidence of pancreatic cancer in diabetic patients, with varying effects observed among different ethnicities (Asian and Western). Due to significant heterogeneity across studies, further interpretation of the relationship between hypoglycemic agents and pancreatic cancer incidence in diabetic patients requires well-adjusted data and better-organized clinical trials.
PubMed: 37497113
DOI: 10.3389/fphar.2023.1193610 -
Communications Medicine Oct 2023Gestational Diabetes Mellitus (GDM) affects approximately 1 in 7 pregnancies globally. It is associated with short- and long-term risks for both mother and baby....
BACKGROUND
Gestational Diabetes Mellitus (GDM) affects approximately 1 in 7 pregnancies globally. It is associated with short- and long-term risks for both mother and baby. Therefore, optimizing treatment to effectively treat the condition has wide-ranging beneficial effects. However, despite the known heterogeneity in GDM, treatment guidelines and approaches are generally standardized. We hypothesized that a precision medicine approach could be a tool for risk-stratification of women to streamline successful GDM management. With the relatively short timeframe available to treat GDM, commencing effective therapy earlier, with more rapid normalization of hyperglycaemia, could have benefits for both mother and fetus.
METHODS
We conducted two systematic reviews, to identify precision markers that may predict effective lifestyle and pharmacological interventions.
RESULTS
There was a paucity of studies examining precision lifestyle-based interventions for GDM highlighting the pressing need for further research in this area. We found a number of precision markers identified from routine clinical measures that may enable earlier identification of those requiring escalation of pharmacological therapy (to metformin, sulphonylureas or insulin). This included previous history of GDM, Body Mass Index and blood glucose concentrations at diagnosis.
CONCLUSIONS
Clinical measurements at diagnosis could potentially be used as precision markers in the treatment of GDM. Whether there are other sensitive markers that could be identified using more complex individual-level data, such as omics, and if these can feasibly be implemented in clinical practice remains unknown. These will be important to consider in future studies.
PubMed: 37794196
DOI: 10.1038/s43856-023-00371-0 -
Diabetes Research and Clinical Practice Aug 2023Lifestyle changes and dietary intervention, including the use of probiotics, can modulate dysbiosis of gut microbiome and contribute to the management of type 2 diabetes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lifestyle changes and dietary intervention, including the use of probiotics, can modulate dysbiosis of gut microbiome and contribute to the management of type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis aim to assess the efficacy of metformin plus probiotics versus metformin alone on outcomes in patients with T2DM.
METHODS
We searched MEDLINE and EMBASE from inception to February 2023 to identify all randomized controlled trials (RCTs), which compared the use of metformin plus probiotics versus metformin alone in adult patients with T2DM. Data were summarized as mean differences (MD) with 95 % confidence interval (CI) and pooled under the random effects model.
FINDINGS
Fourteen RCTs (17 comparisons, 1009 patients) were included in this systematic review. Pooled results show a significant decrease in fasting glucose (FG) (MD = -0.64, 95 % CI = -1.06, -0.22) and HbA1c (MD = -0.29, 95 % CI = -0.47, -0.10) levels in patients with T2DM treated with metformin plus probiotics versus metformin alone. The addition of probiotics to metformin resulted in lower odds of gastrointestinal adverse events (Odds ratio = 0.18, 95 % CI = 0.09, 0.3.8; I = 0 %).
CONCLUSIONS
The addition of probiotics to metformin therapy is associated with improvement in T2DM outcomes. However, high-quality and adequately reported RCTs are needed in the future to confirm our findings.
Topics: Adult; Humans; Metformin; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Probiotics; Fasting
PubMed: 37369280
DOI: 10.1016/j.diabres.2023.110806 -
The Laryngoscope Sep 2023To systematically review and evaluate metformin's potential impact on vestibular schwannoma (VS) growth. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To systematically review and evaluate metformin's potential impact on vestibular schwannoma (VS) growth.
DATA SOURCES
PubMed, Cochrane Library, and Embase.
REVIEW METHODS
A retrospective cohort study was performed on sporadic VS patients undergoing initial observation who had at least two magnetic resonance imaging studies. Patients were stratified by metformin use during the observation period. Primary endpoint was VS growth, defined as at least a 2 mm increase in diameter. Survival free of tumor growth was evaluated between groups. Systematic review and meta-analysis were performed to produce a pooled odds ratio [OR]. Study heterogeneity was assessed and post-hoc power analysis was performed.
RESULTS
A total of 123 patients were included, of which 17% were taking metformin. Median patient age was 56.6 years (range, 25.1-84.5). There were no statistically significant differences between the groups. Survival analysis did not demonstrate a statistically significant difference in time to VS growth between groups (hazard ratio = 0.61, 95% confidence interval [CI] = 0.29-1.29). Furthermore, logistic regression analysis did not demonstrate a statistically significant difference between groups in the odds of VS growth (OR = 0.46, 95% CI = 0.17-1.27). Systematic review identified 3 studies. Meta-analysis suggested that metformin reduces the odds of developing VS growth (pooled OR = 0.45, 95% CI = 0.29-0.71). Studies demonstrated low between-study heterogeneity. Power analysis demonstrated a sample size of 220 patients with equal randomization would be required to prospectively identify a true difference with 80% power.
CONCLUSIONS
Metformin use may reduce the odds of VS growth. A randomized trial would be ideal to identify an unbiased estimate of metformin's effect on VS growth. Laryngoscope, 133:2066-2072, 2023.
Topics: Humans; Adult; Middle Aged; Aged; Aged, 80 and over; Neuroma, Acoustic; Metformin; Retrospective Studies; Magnetic Resonance Imaging; Survival Analysis
PubMed: 36744870
DOI: 10.1002/lary.30601