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Scientific Reports Apr 2024The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through... (Meta-Analysis)
Meta-Analysis
The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.PROSPERO registration no. CRD42023412603.
Topics: Humans; Metformin; Peroxisome Proliferator-Activated Receptors; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Drug Therapy, Combination
PubMed: 38627464
DOI: 10.1038/s41598-024-59390-z -
Cureus Mar 2024A large portion of the world's population is affected by acne vulgaris (AV), with many of these individuals being adolescents. The underlying mechanism of AV is... (Review)
Review
A large portion of the world's population is affected by acne vulgaris (AV), with many of these individuals being adolescents. The underlying mechanism of AV is hyperkeratinization and infection of the pilosebaceous follicle secondary to excessive stimulation of sebaceous glands by androgens. Metformin is a biguanide medication primarily used in efforts to lower patients' sugar levels in the management of type 2 diabetes. It has been proven to reduce levels of circulating androgens in patients with insulin resistance, indicating its potential for treating AV. A search strategy was developed and performed using the databases Ovid Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Controlled Register of Trials (CENTRAL), and Web of Science. The keywords "metformin" and "acne" were searched, along with related Medical Subject Headings (MeSH) and other subject headings. Studies that met the inclusion criteria were controlled trials, published after 2010, and in the English language. Participants with and without comorbidities such as polycystic ovary syndrome (PCOS) were considered. Two independent reviewers screened studies based on predefined criteria and extracted data from each study, which were quantitatively combined. A total of 15 studies were included in this systematic review. Across the 15 studies, there were 1,046 participants, with 13 studies looking exclusively at women with PCOS. Of the remaining two studies, one examined males with altered metabolic profiles, while the other included men and women with moderate AV. Notable risks of bias included studies that did not exclusively state the blindness of the study. Of the studies that were examined, 13 showed that metformin reduces AV, with seven studies showing statistical significance. Acne vulgaris is an inflammatory condition that has plagued patients for years due to the limited treatment options available. The hyperglycemic medication metformin, used in the management of type 2 diabetes, is being explored as a novel therapeutic that can possibly be repurposed for the treatment of AV. The use of metformin in AV is hypothesized to disrupt the proposed linkage between insulin resistance and AV proliferation. This proposed research could offer physicians a new option for the treatment of AV as well as render an alternative AV treatment for patients.
PubMed: 38623111
DOI: 10.7759/cureus.56246 -
Annals of Saudi Medicine 2024No external funding. (Meta-Analysis)
Meta-Analysis Review
No external funding.
Topics: Humans; Metformin; Diabetes Mellitus; Hematologic Neoplasms
PubMed: 38615182
DOI: 10.5144/0256-4947.2024.126 -
Gynecological Endocrinology : the... Dec 2024This study aims to examine the short-term effects of oral metformin (MET) on serum anti-müllerian hormone (AMH) levels and to verify its impact on AMH concentrations in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aims to examine the short-term effects of oral metformin (MET) on serum anti-müllerian hormone (AMH) levels and to verify its impact on AMH concentrations in women with polycystic ovary syndrome (PCOS).
METHODS
The literature search, extending from January 2000 to April 2023, was conducted using databases such as PubMed, Embase, and the Cochrane Central, resulting in the inclusion of 20 studies. These selected studies, evaluated for quality using the Newcastle-Ottawa Scale, investigated changes in AMH levels before and after treatment, with durations ranging from less than three months to over six months. The reported outcomes were quantified as standardized mean differences (SMD) with 95% confidence intervals (CI). This comprehensive systematic review and meta-analysis was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42023420705. The statistical analyses were performed using Review Manager 5.4.1.
RESULTS
① The study incorporated 20 articles, consisting of 12 prospective studies, 7 randomized controlled trials (RCT), and 1 cross-sectional study. ② Serum AMH levels in patients with PCOS diminish subsequent to the oral administration of MET. ③ Across the spectrum of studies analyzed, a pronounced degree of heterogeneity is evident, potentially ascribed to differential parameters including body mass index (BMI), daily pharmacological dosages, the temporal extent of treatment regimens, criteria of PCOS, and detection Methods. ④ The impact of MET on AMH levels exhibits a dose-responsive trend, with escalating doses of MET being associated with progressively greater declines in AMH concentrations in the patient population. ⑤ For women with PCOS receiving MET therapy, a minimum treatment duration of three months may be necessary to observe a reduction in serum AMH levels.
CONCLUSIONS
The results of this meta-analysis indicate that MET treatment exerts a suppressive effect on serum AMH levels in women with PCOS. It appears that a treatment duration of at least three months is required to achieve a significant decrease in AMH concentrations. Furthermore, the influence of MET on AMH is dose-dependent, with higher doses correlating with more pronounced reductions in AMH levels among the patients studied.
Topics: Female; Humans; Anti-Mullerian Hormone; Polycystic Ovary Syndrome; Administration, Oral; Body Mass Index; Metformin; Peptide Hormones
PubMed: 38613449
DOI: 10.1080/09513590.2024.2330655 -
Clinical and Experimental Reproductive... Apr 2024Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder among reproductive-age women. As a leading cause of anovulatory infertility, it complicates...
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder among reproductive-age women. As a leading cause of anovulatory infertility, it complicates fertility treatments, including in vitro fertilization. The widely accepted 2003 Rotterdam diagnostic criteria for PCOS include sub-phenotypes based on variations in androgen excess, ovulatory dysfunction, and polycystic ovarian morphology. In this systematic review, we examined the impacts of inositol and vitamin D on fertility in PCOS. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, we used relevant keywords to comprehensively search databases including PubMed, Google Scholar, and MDPI. From an initial pool of 345 articles, 10 met the inclusion criteria. The articles suggest that vitamin D and inositol, particularly myo-inositol and D-chiro-inositol, may represent therapeutic options for PCOS. Vitamin D influences ovarian follicular development, glucose regulation, and insulin sensitivity. When combined with metformin therapy, it is associated with improved menstrual regularity and ovulation. Inositol is crucial for cellular signaling, energy metabolism, glucose regulation, and fertility. This systematic review underscores the importance of investigating inositol and vitamin D within a PCOS management strategy, given the disorder's prevalence and impacts on fertility and metabolic health. Although these agents show promise, additional research could clarify their mechanisms of action and therapeutic benefits. This review emphasizes the need for exploration of effective treatments to improve the quality of life among individuals with PCOS. Inositol and vitamin D represent potential options, but more studies are required to elucidate their roles in the management of this condition.
PubMed: 38599886
DOI: 10.5653/cerm.2023.06485 -
BMC Endocrine Disorders Mar 2024Several interventional studies have evaluated the potential anti-Mullerian hormone (AMH)-reduction effect of metformin. However, the results are still contradictory. In... (Meta-Analysis)
Meta-Analysis
Effect of metformin on anti-mullerian hormone levels in women with polycystic ovarian syndrome: a systematic review and meta-regression analysis of randomized controlled trials with.
BACKGROUND
Several interventional studies have evaluated the potential anti-Mullerian hormone (AMH)-reduction effect of metformin. However, the results are still contradictory. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of metformin on AMH in the women with with polycystic ovarian syndrome (PCOS).
METHODS
Scopus, PubMed/Medline, Web of Science, Cochrane, and Embase databases were searched using standard keywords to identify all controlled trials investigating the AMH levels following metformin administration. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model analysis for the best estimation of outcomes.
RESULTS
Sixteen studies with 484 participants' were included in this article. The pooled findings showed that AMH levels in the single arm clinical trials were significantly reduced (pooled WMD of -3.06 ng/ml; 95% confidence interval [CI] -4.03 to -2.10; P < 0.001) after use of metformin. Furthermore, compared to the control group, in randomized clinical trials, a reduced significant effect on AMH levels was observed following use of metformin (pooled WMD of -3.47 ng/ml; 95% CI -7.14 to -0.19; P = 0.047). Furthermore, higher reduction in the AMH levels with a metformin dosage ≤ 1500 mg/day and duration of treatment ≤ 12 weeks when compared to higher dosages and duration of intervention, observed in this meta-analysis.
CONCLUSIONS
In conclusion, results this meta-analysis of clinical trials confirms the beneficial effect of the treatment with metformin in the reduction of the AMH levels in women.
Topics: Female; Humans; Polycystic Ovary Syndrome; Anti-Mullerian Hormone; Metformin; Randomized Controlled Trials as Topic; Peptide Hormones; Regression Analysis
PubMed: 38549135
DOI: 10.1186/s12902-024-01570-z -
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 -
International Journal of Endocrinology 2024Metformin is commonly prescribed to treat polycystic ovary syndrome (PCOS) patients, but in some cases, it may not be effective even at high doses or may cause... (Review)
Review
Comparative Effectiveness of Antidiabetic Drugs as an Additional Therapy to Metformin in Women with Polycystic Ovary Syndrome: A Systematic Review of Metabolic Approaches.
BACKGROUND
Metformin is commonly prescribed to treat polycystic ovary syndrome (PCOS) patients, but in some cases, it may not be effective even at high doses or may cause intolerable side effects. Therefore, recent studies have examined the impact of combining metformin with other antidiabetic medications.
METHODS
A systematic search was performed in Scopus, PubMed, Web of Science, and Embase up to 30 June 2023. All interventional studies that assessed the efficacy of different antidiabetic agents were included.
RESULTS
Among the 3488 records found in the primary search, 16 papers were included. Our study showed that dipeptidyl peptidase-4 inhibitors (DPP4i) had the most significant impact on glycemic profile, while thiazolidinediones (TZDs) had the most influence on lipid levels. However, it was observed that patients taking only metformin experienced a greater increase in high-density lipoprotein cholesterol (HDL-C) levels. Glucagon-like peptide-1 receptor agonists (GLP1RAs) effectively modified various anthropometric measurements, such as weight, body mass index, waist circumference, and waist-to-hip ratio. The effects of different antidiabetic drugs on hormone levels were inconclusive, although testosterone levels were more affected by GLP1RA, sodium-glucose cotransporter-2 inhibitors (SGLT2i), and TZDs. None of the combined therapies showed a significant change in blood pressure.
CONCLUSION
Since PCOS is a metabolic disorder, choosing the best combination of antidiabetic drugs in the clinical course of PCOS patients will be very important. Today, it seems that we need a new metabolic approach for better treatment of the metabolic aspects of these patients.
PubMed: 38500709
DOI: 10.1155/2024/9900213 -
Diabetes Therapy : Research, Treatment... May 2024Insulin is the first-line pharmacologic therapy for women with diabetes in pregnancy. However, conducting well-designed randomized clinical trials (RCTs) and achieving... (Review)
Review
INTRODUCTION
Insulin is the first-line pharmacologic therapy for women with diabetes in pregnancy. However, conducting well-designed randomized clinical trials (RCTs) and achieving recommended glycemic targets remains a challenge for this unique population. This systematic literature review (SLR) aimed to understand the evidence for insulin use in pregnancy and the outcome metrics most often used to characterize its effect on glycemic, maternal and fetal outcomes in gestational diabetes mellitus (GDM) and in pregnant women with diabetes.
METHODS
An SLR was conducted using electronic databases in Medline, EMBASE via Ovid platform, evidence-based medicine reviews (2010-2020) and conference proceedings (2018-2019). Studies were included if they assessed the effect of insulin treatment on glycemic, maternal or fetal outcomes in women with diabetes in pregnancy. Studies on any type of diabetes other than gestational or pre-existing diabetes as well as non-human studies were excluded.
RESULTS
In women diagnosed with GDM or pre-existing diabetes, most studies compared treatment of insulin with metformin (n = 35) followed by diet along with lifestyle intervention (n = 24) and glibenclamide (n = 12). Most studies reporting on glycemic outcomes compared insulin with metformin (n = 22) and glibenclamide (n = 4). Fasting blood glucose was the most reported clinical outcome of interest. Among the studies reporting maternal outcomes, method of delivery and delivery complications were most commonly reported. Large for gestational age, stillbirth and perinatal mortality were the most common fetal outcomes reported.
CONCLUSION
This SLR included a total of 108 clinical trials and observational studies with diverse populations and treatment arms. Outcomes varied across the studies, and a lack of consistent outcome measures to manage diabetes in pregnant women was observed. This elucidates a need for global consensus on study design and standardized clinical, maternal and fetal outcomes metrics.
PubMed: 38494573
DOI: 10.1007/s13300-024-01541-6 -
Cancer Medicine Mar 2024Due to encouraging pre-clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Due to encouraging pre-clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin, angiotensin-converting enzyme [ACE] inhibitors, statins, and metformin) approved to treat diseases such as hypertension, hyperlipidemia, and diabetes mellitus to the field of oncology. Moreover, given growing costs with cancer care, these medications have offered a potentially more affordable avenue to treat or prevent recurrence of cancer. We sought to investigate the anti-cancer effects of drugs repurposed from cardiology or anti-inflammatories to treat cancer. We specifically evaluated the following drug classes: HMG-CoA reductase inhibitors (statins), cyclo-oxygenase inhibitors, aspirin, metformin, and both angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors. We also included non-steroidal anti-inflammatory drugs (NSAIDs) because they exert a similar mechanism to aspirin by blocking prostaglandins and reducing inflammation that is thought to promote the development of cancer.
METHODS
We performed a systematic literature review using PubMed and Web of Science with search terms including "aspirin," "NSAID," "statin" (including specific statin drug names), "metformin," "ACE inhibitors," and "ARBs" (including specific anti-hypertensive drug names) in combination with "cancer." Searches were limited to human studies published between 2000 and 2023.
MAIN OUTCOMES AND MEASURES
The number and percentage of studies reported positive results and pooled estimates of overall survival, progression-free survival, response, and disease-free survival.
RESULTS
We reviewed 3094 titles and included 67 randomized clinical trials. The most common drugs that were tested were metformin (n = 21; 30.9%), celecoxib (n = 20; 29.4%), and simvastatin (n = 8; 11.8%). There was only one study that tested cardiac glycosides and none that studied ACE inhibitors. The most common tumor types were non-small-cell lung cancer (n = 19; 27.9%); breast (n = 8; 20.6%), colorectal (n = 7; 10.3%), and hepatocellular (n = 6; 8.8%). Most studies were conducted in a phase II trial (n = 38; 55.9%). Most studies were tested in metastatic cancers (n = 49; 72.1%) and in the first-line setting (n = 36; 521.9%). Four studies (5.9%) were stopped early because of difficulty with accrual. The majority of studies did not demonstrate an improvement in either progression-free survival (86.1% of studies testing progression-free survival) or in overall survival (94.3% of studies testing overall survival). Progression-free survival was improved in five studies (7.4%), and overall survival was improved in three studies (4.4%). Overall survival was significantly worse in two studies (3.8% of studies testing overall survival), and progression-free survival was worse in one study (2.8% of studies testing progression-free survival).
CONCLUSIONS AND RELEVANCE
Despite promising pre-clinical and population-based data, cardiovascular drugs and anti-inflammatory medications have overall not demonstrated benefit in the treatment or preventing recurrence of cancer. These findings may help guide future potential clinical trials involving these medications when applied in oncology.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Carcinoma, Non-Small-Cell Lung; Angiotensin Receptor Antagonists; Lung Neoplasms; Randomized Controlled Trials as Topic; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents; Aspirin; Antihypertensive Agents; Metformin
PubMed: 38491813
DOI: 10.1002/cam4.7049