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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 -
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 -
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 -
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 -
Cureus Nov 2023Type 2 diabetes mellitus (T2DM) is a worldwide epidemic that is only increasing as the years progress, and as of 2019, affecting over 37 million. T2DM is a chronic... (Review)
Review
Type 2 diabetes mellitus (T2DM) is a worldwide epidemic that is only increasing as the years progress, and as of 2019, affecting over 37 million. T2DM is a chronic condition caused by reduced insulin secretion and increased insulin resistance. Due to insulin not operating at optimal conditions, blood glucose rises and remains high, thus disturbing metabolic hemostasis. Many complications can arise from T2DM, such as coronary vascular disease, kidney damage, eye damage, and, quite significantly, dementia. It is theorized that dementia from T2DM stems from the fact that the brain is susceptible to hyperglycemic conditions, which are promoted by the increase in insulin resistance of target cells in the central nervous system. This directly affects cognitive processes and memory, which correlates to decreased temporal and front lobes volume. The risk of diabetic complications can be minimized with therapeutic interventions such as oral-antidiabetic (OAD) agents and insulin. Several OADs are on the market, but the first-line agent is metformin, a biguanide that decreases glucose production and increases insulin sensitivity. This paper aims to determine if currently prescribed OADs can help slow cognitive decline and reduce the risk and incidence of dementia as a complication of T2DM. Studies found that, for the most part, all OADs except sulfonylureas (SU) significantly slowed the decline of cognitive function and reduced the risk and incidence of dementia. SU's were shown to increase the risk of dementia in most studies. Of all the OADs, thiazolidinediones may be the most beneficial drug class for reducing the risk of dementia in T2DM patients. Future research should focus on whether early intervention with specific classes of OADs can not only improve glycemic control, leading to decreased hyperglycemia but also prevent the build-up of damaged brain tissue and help to reduce the risk and incidence of dementia in patients with T2DM.
PubMed: 38152822
DOI: 10.7759/cureus.49515 -
Frontiers in Oncology 2024There is evidence of a modest reduction in skin cancer risk among metformin users. However, no studies have further examined the effects of metformin on melanoma...
BACKGROUND
There is evidence of a modest reduction in skin cancer risk among metformin users. However, no studies have further examined the effects of metformin on melanoma survival and safety outcomes. This study aimed to quantitatively summarize any influence of metformin on the overall survival (OS) and immune-related adverse effects (irAEs) in melanoma patients.
METHODS
Selection criteria: The inclusion criteria were designed based on the PICOS principles. Information sources: PubMed, EMBASE, Cochrane Library, and Web of Science were searched for relevant literature published from the inception of these databases until November 2023 using and as keywords. Survival outcomes were OS, progression-free survival (PFS), recurrence-free survival (RFS), and mortality; the safety outcome was irAEs. Risk of bias and data Synthesis: The Cochrane tool for assessing the risk of bias in randomized trial 2 (RoB2) and methodological index for non-randomized studies (MINORS) were selected to assess the risk of bias. The Cochrane Q and statistics based on Stata 15.1 SE were used to test the heterogeneity among all studies. Funnel plot, Egger regression, and Begg tests were used to evaluate publication bias. The leave-one-out method was selected as the sensitivity analysis tool.
RESULTS
A total of 12 studies were included, involving 111,036 melanoma patients. The pooled HR for OS was 0.64 (95% CI [0.42, 1.00], p = 0.004, I 73.7%), HR for PFS was 0.89 (95% CI [0.70, 1.12], p = 0.163, I 41.4%), HR for RFS was 0.62 (95% CI [0.26, 1.48], p = 0.085, I 66.3%), and HR for mortality was 0.53 (95% CI [0.46, 0.63], p = 0.775, I 0.0%). There was no significant difference in irAEs incidence (OR = 1.01; 95% CI [0.42, 2.41]; p = 0.642) between metformin and no metformin groups.
DISCUSSION
The improvement in overall survival of melanoma patients with metformin may indirectly result from its diverse biological targets and beneficial effects on multiple systemic diseases. While we could not demonstrate a specific improvement in the survival of melanoma patients, the combined benefits and safety of metformin for patients taking the drug are worthy of recognition.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024518182.
PubMed: 38846983
DOI: 10.3389/fonc.2024.1399693 -
Frontiers in Endocrinology 2023PCOS is a syndrome of ovarian dysfunction associated with recurrent pregnancy loss. Several correlating factors have been investigated that influence the risk of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
PCOS is a syndrome of ovarian dysfunction associated with recurrent pregnancy loss. Several correlating factors have been investigated that influence the risk of pregnancy loss in PCOS. However, uncertainty remains about their contribution to pregnancy loss and prognosis. This review of literature aims to identify what is known and what requires further investigation on the relationship between PCOS and recurrent pregnancy loss, to guide future research and optimize medical guidance throughout pregnancy.
STUDY DESIGN
a review of literature was performed on several search engines using the following terms; polycystic ovarian syndrome, PCOS, recurrent pregnancy loss, recurrent miscarriage, RPL, aborted fetus, abortus provocatus, miscarriage and habitual abortion.
RESULTS
37 articles were included; 3 systematic reviews, 1 meta-analysis, 2 randomized controlled trials, 6 prospective cohort studies, 22 case-control studies and 3 case series. The main objectives investigated by studies were pregnancy complications, pregnancy loss and live birth in the PCOS population.
CONCLUSION
Studies that investigated the relationship between PCOS and recurrent pregnancy loss are few and inconsistent and warrant further research. Factors apt for further investigation include the extent to which PCOS phenotypes, BMI, obesity, insulin resistance, hyperandrogenemia, SHBG, hs-CRP, CTRP6, adiponectin, plasma leptin, homocysteine, AMH and thrombophilia contribute to further risk of miscarriage. Other factors requiring further exploration in relation to risk for miscarriage in PCOS patient with RPL include sOB-R, PAI-Fx and the Factor-V-Leiden mutations.
Topics: Pregnancy; Female; Humans; Polycystic Ovary Syndrome; Prospective Studies; Abortion, Habitual; Thrombophilia; Obesity
PubMed: 38027110
DOI: 10.3389/fendo.2023.1183060 -
Women's Health (London, England) 2024Polycystic ovary syndrome is a common reproductive endocrine condition that affects women of fertile age and is characterized by three main features, including... (Review)
Review
Polycystic ovary syndrome is a common reproductive endocrine condition that affects women of fertile age and is characterized by three main features, including hyperandrogenism, chronic anovulation, and polycystic ovaries. In addition, half of women with polycystic ovary syndrome have insulin resistance, and obesity or overweight, type 2 diabetes, hypertension, and hyperlipidemia are the most common metabolic abnormalities affecting (30%) women with polycystic ovary syndrome. Weight loss is regarded as the first-line treatment as it can potentially improve polycystic ovary syndrome parameters (androgen levels, menstrual cyclicity, lipid and glucose metabolism). However, achieving and maintaining weight loss can be challenging, and pharmacological agents could be essential to achieve optimal glycemic control and improve the endocrine disturbance associated with polycystic ovary syndrome. Glucagon-like peptide-1 receptor agonist has been demonstrated as monotherapy or in combination with metformin for managing obesity and insulin resistance associated with polycystic ovary syndrome. Yet, its effect on endocrine and metabolic parameters remains elusive, and further research is needed to close the gap. The aim is to evaluate the efficacy of glucagon-like peptide-1 receptor agonist monotherapy and/or a combined treatment between glucagon-like peptide-1 receptor agonist and metformin for improving anthropometric measurements, endocrine and metabolic parameters in lean and obese women with polycystic ovary syndrome. A systematic review of longitudinal cohort studies was conducted across databases including Ovid Medline, PubMed Central, and Cochrane Library between 2015 and 2022. Eligible studies included participants with polycystic ovary syndrome diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health criteria. A total of eight studies including 486 patients with polycystic ovary syndrome were analyzed. The mean age was between 18 and 45 years with mean follow-up period between 12 and 32 weeks. In all these studies, results were comparable for the reduction in body mass index, waist circumference, fat mass, and visceral fat mass; however, it was more in combination therapy versus comparator. In conclusion, glucagon-like peptide-1 receptor agonists effectively reduce body weight and improve some of the endocrine and metabolic parameters of polycystic ovary syndrome. A combined treatment with glucagon-like peptide-1 receptor agonist and metformin had significant effects on weight loss and favorable results on endocrine and metabolic parameters, yet further research is needed to discover the long-term safety of combined therapy in women diagnosed with polycystic ovary syndrome and obesity or overweight.
Topics: Female; Humans; Infant; Male; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor Agonists; Insulin Resistance; Longitudinal Studies; Metformin; Obesity; Overweight; Polycystic Ovary Syndrome; United States; Weight Loss
PubMed: 38444070
DOI: 10.1177/17455057241234530 -
BMC Endocrine Disorders Nov 2023Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of childbearing age. Randomized controlled trials (RCTs) have reported that... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of childbearing age. Randomized controlled trials (RCTs) have reported that exenatide and metformin are effective in the treatment of PCOS. In this meta-analysis, we aimed to compare the effectiveness and safety of exenatide alone or in combination with metformin versus metformin in patients suffering from PCOS.
METHODS
RCTs of exenatide therapy were identified through a search of electronic databases in November 2022 and updated in October 2023. Eligible studies were identified independently by the reviewers. Outcomes were analysed with Revman 5.4.
RESULTS
Nine RCTs among 214 studies on 1059 women with PCOS were included in the analysis, and among the nine RCTs, eight studies compared exenatide with metformin. Our meta-analysis demonstrated that exenatide was more effective than metformin in terms of pregnancy rate (RR 1.85 [95% CI 1.19,2.86] P = 0.006), sex hormone-binding globulin (SHBG) (MD 5 [95% CI 3.82,6.18] P < 0.001), and follicle-stimulating hormone (FSH) (MD 0.82 [95% 0.41,1.24] P < 0.001). The reductions in total testosterone (TT) (SMD -0.43 [95% CI -0.84, -0.03] P = 0.04) was more significant after treatment with exenatide than after treatment with metformin. In terms of safety, exenatide had a lower diarrhea rate (RR 0.11 [95% CI 0.01, 0.84]) than metformin. In the other three studies, exenatide plus metformin was compared with metformin. Exenatide combined with metformin was more effective in improving SHBG (MD 10.38[95%CI 6.7,14.06] P < 0.001), Matsuda index (MD 0.21[95%CI 0.05,0.37]) and reducing free androgen index (FAI) (MD -3.34 [-4.84, -1.83] P < 0.001), Weight (MD -2.32 [95%CI -3.89, -0.66]) and WC (MD-5.61[95%CI -8.4, -2.82] P < 0.001). The incidence of side effects between exenatide plus metformin and metformin was not statistically significant.
CONCLUSIONS
Exenatide alone or in combination with metformin is more effective than metformin for women with PCOS. Considering the evidence on effectiveness and safety, exenatide alone or in combination with metformin may be a better treatment approach than metformin for women with PCOS.
TRIAL REGISTRATION
INPLASY https://inplasy.com/inplasy-protocols/ ID: 10.37766/inplasy2022.11.0055.
Topics: Pregnancy; Female; Humans; Metformin; Polycystic Ovary Syndrome; Exenatide; Pregnancy Rate; Hypoglycemic Agents
PubMed: 37974132
DOI: 10.1186/s12902-023-01497-x -
Gynecologic Oncology Mar 2024Several abstract studies have demonstrated that metformin may be beneficial for preventing and treating endometrial cancer (EC), while the results have been inconsistent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several abstract studies have demonstrated that metformin may be beneficial for preventing and treating endometrial cancer (EC), while the results have been inconsistent and inconclusive. This systematic review and meta-analysis aimed to investigate the association between metformin use and the incidence and mortality of endometrial cancer in diabetic patients.
METHODS
A systematic literature search was performed in Pubmed, EMBASE, Web of Science, Cochrane Library, SinoMed, CNKI, Wanfang Data, and VIP from inception to November 2022. The outcome measures were hazard ratios (HRs) comparing the EC incidence and mortality in patients with type 2 diabetes mellitus (T2DM) on metformin and non-metformin. A random or fixed-effects model was applied for data analysis, and subgroup analysis was performed to look for factors of heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessed the evidence's certainty.
RESULTS
Eleven studies reported data on EC incidence. The pooled results suggested that the use of metformin was associated with a significantly higher incidence of EC (HR = 1.17, 95% CI 1.09-1.26, P < 0.0001). Further, seventeen studies were included for survival analysis. The pooled data showed that metformin could significantly decrease all-cause mortality (HR = 0.62, 95% CI 0.52-0.74, P < 0.00001) and endometrial cancer-specific mortality (HR = 0.95, 95% CI 0.90, 1.00, P = 0.03). Finally, we noted that metformin was associated with significantly improving the progression-free survival (PFS) of EC patients with T2DM (HR = 0.55, 95% CI 0.44, 0.68, P < 0.00001).
CONCLUSIONS
This meta-analysis did not prove that metformin was beneficial for preventing EC. However, metformin could reduce their mortality risk and prolong the progression-free survival time of EC patients with T2DM.
Topics: Female; Humans; Metformin; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Endometrial Neoplasms; Risk; Prognosis
PubMed: 38246042
DOI: 10.1016/j.ygyno.2024.01.007