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1.
BMJ Open ; 11(8): e051884, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408057

RESUMO

OBJECTIVES: The aims of this study were to describe the following: (1) the time to change of therapy in patients with type 2 diabetes who had initiated metformin monotherapy as first-line treatment and (2) the sequence in which subsequent therapeutic regimens were introduced. DESIGN: Cohort study. SETTING: National study based on linked data from the New Zealand Ministry of Health's National Collections of health and pharmaceutical dispensing data. PARTICIPANTS: People with type 2 diabetes mellitus who initiated metformin monotherapy between 1 January 2006 and 30 September 2014 (n=93 874). PRIMARY OUTCOME MEASURES: Cumulative incidence curves were plotted to show the time taken to move from one regimen to another, while sunburst plots were used to illustrate the sequence in which regimens were introduced. RESULTS: About 10% and 35% of cohort members had moved to a second regimen 1 year and 5 years, respectively, after initiating metformin monotherapy; the majority received a regimen recommended by New Zealand treatment guidelines (mostly metformin and a sulphonylurea). Of those who started a recommended second regimen, 37% and 67% had moved to a third regimen after 1 and 5 years, respectively; the corresponding proportions for those who started an 'other' (not listed as recommended) second regimen were 53% and 75%. Most of those who received a third regimen after a recommended second regimen were dispensed an 'other' third regimen. Of those who moved to a third regimen from an 'other' second regimen, similar proportions received recommended and 'other' third regimens. CONCLUSIONS: Real-world type 2 diabetes treatment patterns in New Zealand are complex and not always consistent with guidelines.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Estudos de Coortes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Nova Zelândia/epidemiologia
2.
Reprod Health ; 18(1): 171, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34407851

RESUMO

BACKGROUND: Multiple oral insulin-sensitizing agents, such as metformin, thiazolidinediones, inositols, and berberine, have been proven safe and efficacious in improving the endocrine, metabolic, and reproductive abnormalities seen in polycystic ovary syndrome (PCOS), providing more options for healthcare providers and patients. These oral insulin sensitizers are more convenient, practical, and economic than agents that need to be injected. A comparison of the clinical effectiveness of the four different classes of oral insulin sensitizers in PCOS has not been explored, leading to clinical uncertainty about the optimal treatment pathway. The present study aims to compare the effects of oral insulin sensitizers on endocrine and metabolic profiles in women with PCOS. METHODS: We identified randomized controlled trials for PCOS from a variety of databases, published from January 2005 to October 2020. Outcomes included changes in menstrual frequency, improvements in hyperandrogenism and glucolipid metabolism and adverse side effects. A random-effects network meta-analysis was performed. RESULTS: Twenty-two trials comprising 1079 patients with PCOS were included in this study. Compared with metformin, treatment with myo-inositol + D-chiro-inositol was associated with a greater improvement in menstrual frequency (odds ratio 14.70 [95% confidence interval (CI) 2.31-93.58]). Myo-inositol + D-chiro-inositol and metformin + thiazolidinediones combination therapies were superior to respective monotherapies in reducing total testosterone levels. Thiazolidinediones, metformin + thiazolidinediones, and myo-inositol + D-chiro-inositol were associated with a lower insulin resistance index (HOMA-IR) compared with that in metformin alone (mean differences: - 0.72 [95% CI (- 1.11)-(- 0.34)] to - 0.89 [95% CI (- 1.460)-(- 0.32)]). Metformin + thiazolidinediones treatment was associated with lower triglyceride levels compared with that in metformin and thiazolidinediones monotherapy, while thiazolidinediones was superior to metformin in increasing high-density lipoprotein cholesterol and decreasing fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, and gastrointestinal adverse events. CONCLUSIONS: Ours is the first study to report that for women with PCOS, myo-inositol combined with D-chiro-inositol and metformin combined with thiazolidinediones appear superior to metformin alone in improving insulin resistance and decreasing total testosterone. Myo-inositol combined with D-chiro-inositol is particularly efficacious in menstrual recovery. Thiazolidinediones and metformin combined with thiazolidinediones improve lipid metabolism better than metformin alone. Trial registration PROSPERO CRD42020211524.


Assuntos
Berberina , Resistência à Insulina , Metformina , Síndrome do Ovário Policístico , Tiazolidinedionas , Tomada de Decisão Clínica , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Inositol/uso terapêutico , Insulina , Metaboloma , Metformina/uso terapêutico , Metanálise em Rede , Síndrome do Ovário Policístico/tratamento farmacológico , Tiazolidinedionas/uso terapêutico , Incerteza
3.
Acta Oncol ; 60(9): 1146-1153, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34338111

RESUMO

BACKGROUND: The prognosis of pancreatic cancer is poor and new treatment strategies are urgently needed. To identify non-cancer drugs that could be re-purposed for cancer, we investigated the association between the use of selected drugs and cancer-specific mortality in a nationwide cohort of pancreatic cancer patients. MATERIAL AND METHODS: The study is based on linkage between the Cancer Registry of Norway and the Norwegian Prescription Database, comprising 2614 pancreatic cancer patients diagnosed between 2007 and 2014. We evaluated the association between use at diagnosis of a pre-defined list of non-cancer drugs, including metformin, antihypertensives, and statins, and pancreatic cancer-specific mortality, using Cox regression. Patients were defined as users of a particular drug if it was prescribed before diagnosis, and the prescription covered the date of diagnosis. RESULTS: In total, 2096 (80.2%) patients died from pancreatic cancer; median survival was 6 months. Statin users (n = 621) had lower mortality (hazard ratio (HR): 0.86; 95% confidence interval (CI) 0.76-0.97) compared to non-users (n = 1993). This association was more pronounced (P-heterogeneity 0.062) in users of hydrophilic (n = 37, HR: 0.61; 95% CI 0.42-0.90) than lipophilic (n = 587, HR: 0.87; 95% CI 0.78-0.98) statins. An indication for lower mortality (HR: 0.85; 95% CI 0.69-1.05) was observed in users of non-selective beta-blockers (n = 113) compared to non-users (n = 2501). Notably, when compared to users of other antihypertensives (n = 643), users of non-selective beta-blockers (n = 40) had lower mortality (HR 0.67; 95% CI 0.47-0.96). The use of other drugs, including selective beta-blockers and metformin, was not associated with mortality. CONCLUSION: The findings suggest an association between the use of statins and non-selective beta-blockers and reduced pancreatic cancer mortality, and add to the literature supporting the design of randomised clinical trials to evaluate those drugs in the management of pancreatic cancer.


Assuntos
Adenocarcinoma , Inibidores de Hidroximetilglutaril-CoA Redutases , Metformina , Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Estudos de Coortes , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Metformina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Sistema de Registros
4.
BMJ Open ; 11(8): e044283, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373290

RESUMO

INTRODUCTION: Innovation through the repurposing of generic drugs encloses several advantages when compared with the process of developing new drugs from scratch. Metformin is an established and inexpensive antidiabetic drug for which anticancer properties have been hypothesised. A systematic review of observational studies found promising results for metformin related to breast cancer in women with diabetes. Although the number of randomised clinical trials of metformin for the treatment of breast cancer increased over the last decades, the overall landscape of those studies in this heterogeneous field remains unclear. Hence, we designed the present scoping review protocol to map the literature on randomised clinical trials of metformin in the treatment of breast cancer to determine the value and scope of future systematic reviews on this subject and identify research gaps. METHODS: We will search MEDLINE (via PubMed), EMBASE, CENTRAL, LILACS, Web of Science and sources of grey literature. We will include any randomised clinical trial of metformin for the treatment of breast cancer in adult women, and will not impose restrictions regarding context, language or publication date. Two independent reviewers will screen and select studies, and chart the data. We will structure the presentation of our results based on the molecular types of breast cancer, their stages and treatment modalities. ETHICS AND DISSEMINATION: As a literature review, this study is exempt from ethics approval. Findings will be disseminated through presentations in conferences and a peer-reviewed publication. OPEN SCIENCE FRAMEWORK REGISTRATION: osf.io/yquba.


Assuntos
Neoplasias da Mama , Metformina , Neoplasias da Mama/tratamento farmacológico , Atenção à Saúde , Feminino , Humanos , Metformina/uso terapêutico , Revisão por Pares , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
5.
Artigo em Inglês | MEDLINE | ID: mdl-34444016

RESUMO

Objective: To assess the risk of subsequent miscarriage in pregnant women with a prior diagnosis of polycystic ovarian syndrome (PCOS). Methods: Using a nationwide, population-based database (Taiwan National Health Insurance Research Database) during 1998-2012, the study retrieved 1,000,000 randomly-sampled insured citizens as research subjects. The women with a diagnosis of pre-pregnancy PCOS (n = 13,562) who had chromosomal anomalies, artificial abortion, inconsistent diagnoses, and who were initially diagnosed with PCOS at >45 or <15 year-old were excluded, respectively. The records of gynecologic ultrasonography and/or blood tests were checked to verify the accuracy of the diagnoses of both PCOS and miscarriage (ICD-9 CM codes). After pregnancy, every woman with prior PCOS was age-matched to four women without prior PCOS. Results: Pregnant women with prior PCOS (the case group; n = 1926) and those without prior PCOS (the control group; n = 7704) were compared. The incidence of subsequent miscarriage was much higher in the case group compared with the control group (33.80% vs. 4.09%, p < 0.0001). Logistic regression analysis revealed that the risk of subsequent miscarriage was significantly higher in the case group than the control group (odds ratio [OR] 11.98; 95% CI 10.34-13.87, p < 0.0001), and the result remained similar while adjusted with covariates (adjusted OR 11.97; 95% CI 10.27-13.95, p < 0.0001). In the case group, the patient who used metformin had a lower risk of subsequent miscarriage (adjusted OR 9.53; 95% CI 6.69-13.57) when compared with those who did not receive metformin treatment (adjusted OR 12.13; 95% CI 10.38-14.18). Conclusion: For pregnant women, a pre-pregnancy diagnosis of PCOS is an independent and significant risk factor for subsequent miscarriage. The risk of subsequent miscarriage is reduced by about 1/4 for the PCOS patients who undergo metformin treatment compared with those who do not.


Assuntos
Aborto Espontâneo , Metformina , Síndrome do Ovário Policístico , Aborto Espontâneo/epidemiologia , Adolescente , Feminino , Humanos , Metformina/uso terapêutico , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Gravidez , Gestantes , Fatores de Risco
6.
Medicine (Baltimore) ; 100(31): e26622, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397797

RESUMO

BACKGROUND: Several previous randomized controlled trials (RCTs) evaluated the efficacy of metformin combined with simvastatin in the treatment of polycystic ovary syndrome (PCOS), yet the results of the researches are not consistent. It is necessary to conduct a meta-analysis to explore the efficacy and safety of metformin combined with simvastatin in the treatment of PCOS, to provide evidence supports for the treatment of PCOS. METHODS: We searched PubMed, EMbase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and Chinese biomedical literature databases online to identify the RCTs evaluating the efficacy of metformin combined with simvastatin in the treatment of PCOS. Standardized mean difference (SMD) and 95% confidence interval (95% CI) were calculated to evaluate the synthesized effects. RESULTS: Nine RCTs with a total of 746 PCOS patients were included. The synthesized results indicated that the combined use of metformin and simvastatin are more beneficial to reduce the total cholesterol (SMD -2.66, 95% CI -3.65 to -1.66), triglycerides (SMD -1.25, 95% CI -2.02 to -0.49), low density lipoprotein (SMD -2.91, 95% CI -3.98 to -1.84), testosterone (SMD -0.64, 95% CI -1.13 to -0.15), fasting insulin (SMD -1.17, 95% CI -2.09 to -0.26) than metformin alone treatment in PCOS patients (all P < .001), and there was no significant difference in the high density lipoprotein (SMD -0.05, 95% CI -0.56-0.46), luteinizing hormone (SMD -0.58, 95% CI -1.66 to -0.50), follicle stimulating hormone (SMD 0.41, 95% CI -0.78-1.59), prolactin (SMD -1.38, 95% CI -2.93-0.17), fasting blood sugar (SMD 0.23, 95% CI -0.52-0.97), and insulin sensitivity index (SMD -0.17, 95% CI -0.48-0.15) between experimental and control groups (all P > .05). CONCLUSIONS: Metformin combined with simvastatin is superior to metformin alone in the treatment of PCOS patients with more advantages in improving the levels of sex hormones, blood lipids, and blood sugar. However, the safety of this therapy still needs to be further explored in clinical studies with high-quality and large samples.


Assuntos
Metformina/uso terapêutico , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/tratamento farmacológico , Sinvastatina/uso terapêutico , Glicemia/metabolismo , Colesterol/sangue , Quimioterapia Combinada/efeitos adversos , Feminino , Hormônios Esteroides Gonadais/sangue , Humanos , Insulina/sangue , Lipoproteínas LDL/sangue , Metformina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sinvastatina/efeitos adversos , Triglicerídeos/sangue
7.
FASEB J ; 35(9): e21862, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34416035

RESUMO

Loss of muscle mass and strength after disuse followed by impaired muscle recovery commonly occurs with aging. Metformin (MET) and leucine (LEU) individually have shown positive effects in skeletal muscle during atrophy conditions but have not been evaluated in combination nor tested as a remedy to enhance muscle recovery following disuse atrophy in aging. The purpose of this study was to determine if a dual treatment of metformin and leucine (MET + LEU) would prevent disuse-induced atrophy and/or promote muscle recovery in aged mice and if these muscle responses correspond to changes in satellite cells and collagen remodeling. Aged mice (22-24 months) underwent 14 days of hindlimb unloading (HU) followed by 7 or 14 days of reloading (7 or 14 days RL). MET, LEU, or MET + LEU was administered via drinking water and were compared to Vehicle (standard drinking water) and ambulatory baseline. We observed that during HU, MET + LEU resolved whole body grip strength and soleus muscle specific force decrements caused by HU. Gastrocnemius satellite cell abundance was increased with MET + LEU treatment but did not alter muscle size during disuse or recovery conditions. Moreover, MET + LEU treatment alleviated gastrocnemius collagen accumulation caused by HU and increased collagen turnover during 7 and 14 days RL driven by a decrease in collagen IV content. Transcriptional pathway analysis revealed that MET + LEU altered muscle hallmark pathways related to inflammation and myogenesis during HU. Together, the dual treatment of MET and LEU was able to increase muscle function, satellite cell content, and reduce collagen accumulation, thus improving muscle quality during disuse and recovery in aging.


Assuntos
Envelhecimento , Colágeno/metabolismo , Leucina/uso terapêutico , Metformina/uso terapêutico , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/prevenção & controle , Células Satélites de Músculo Esquelético/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Fibrose/tratamento farmacológico , Elevação dos Membros Posteriores , Imunoglobulina G/análise , Leucina/farmacologia , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Metformina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Desenvolvimento Muscular/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Força Muscular/efeitos dos fármacos , Músculo Esquelético/citologia , Músculo Esquelético/patologia , Atrofia Muscular/patologia , Tamanho do Órgão/efeitos dos fármacos , RNA-Seq , Células Satélites de Músculo Esquelético/citologia , Células Satélites de Músculo Esquelético/patologia , Transdução de Sinais/efeitos dos fármacos
8.
Front Endocrinol (Lausanne) ; 12: 587801, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367059

RESUMO

Metformin is the first-line medication for type 2 diabetes, but it also has a long history of improved outcomes in infectious diseases, such as influenza, hepatitis C, and in-vitro assays of zika. In the current Covid-19 pandemic, which has rapidly spread throughout the world, 4 observational studies have been published showing reduced mortality among individuals with home metformin use. There are several potential overlapping mechanisms by which metformin may reduce mortality from Covid-19. Metformin's past anti-infectious benefits have been both against the infectious agent directly, as well as by improving the underlying health of the human host. It is unknown if the lower mortality suggested by observational studies in patients infected with Covid-19 who are on home metformin is due to direct activity against the virus itself, improved host substrate, or both.


Assuntos
COVID-19/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Humanos , Resultado do Tratamento
9.
J Transl Med ; 19(1): 349, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399790

RESUMO

BACKGROUND: Silicosis is one of the most common occupational pulmonary fibrosis caused by respirable silica-based particle exposure, with no ideal drugs at present. Metformin, a commonly used biguanide antidiabetic agent, could activate AMP-activated protein kinase (AMPK) to exert its pharmacological action. Therefore, we sought to investigate the role of metformin in silica-induced lung fibrosis. METHODS: The anti-fibrotic role of metformin was assessed in 50 mg/kg silica-induced lung fibrosis model. Silicon dioxide (SiO2)-stimulated lung epithelial cells/macrophages and transforming growth factor-beta 1 (TGF-ß1)-induced differentiated lung fibroblasts were used for in vitro models. RESULTS: At the concentration of 300 mg/kg in the mouse model, metformin significantly reduced lung inflammation and fibrosis in SiO2-instilled mice at the early and late fibrotic stages. Besides, metformin (range 2-10 mM) reversed SiO2-induced cell toxicity, oxidative stress, and epithelial-mesenchymal transition process in epithelial cells (A549 and HBE), inhibited inflammation response in macrophages (THP-1), and alleviated TGF-ß1-stimulated fibroblast activation in lung fibroblasts (MRC-5) via an AMPK-dependent pathway. CONCLUSIONS: In this study, we identified that metformin might be a potential drug for silicosis treatment.


Assuntos
Metformina , Fibrose Pulmonar , Proteínas Quinases Ativadas por AMP , Animais , Transição Epitelial-Mesenquimal , Fibroblastos , Humanos , Pulmão , Metformina/farmacologia , Metformina/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Dióxido de Silício/toxicidade , Fator de Crescimento Transformador beta1
10.
Bioengineered ; 12(1): 4757-4767, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34334083

RESUMO

Metformin, a common clinical drug used to treat diabetes mellitus, is found with potential antiobese actions as reported in increasing evidences. However, the detailed mechanisms of metformin-antiobesity-related hypertension remain unrevealed. We have utilized the bioinformatics strategy, including network pharmacology and molecular docking analyses, to uncover pharmacological targets and molecular pathways of bioactive compounds against clinical disorders, such as cancers, coronavirus disease 2019. In this report, the in-silico approaches using network pharmacology and molecular docking was utilized to identify the core targets, pharmacological functions and mechanisms of metformin against obesity-related hypertension. The networking analysis identified 154 differentially expressed genes of obesity and hypertension, and 21 interaction genes, 6 core genes of metformin treating obesity-related hypertension. As results, molecular docking findings indicated the binding capability of metformin with key proteins, including interleukin 6 (IL-6) and chemokine (C-C motif) Ligand 2 (CCL2) expressed in obesity- and hypertension-dependent tissues. Metformin-exerted antihypertension/obesity actions involved in metabolic regulation, inflammatory suppression. And antihypertension/obesity mechanisms of metformin were revealed, including regulation of inflammatory and immunological signaling pathways for ameliorating microenvironmental homeostasis in targeting tissues. In conclusion, our current bioinformatics findings have uncovered all pharmacological targets, biological functions and signaling pathways of metformin treating obesity-related hypertension, thus promoting its clinical application in future.


Assuntos
Hipertensão/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Biologia Computacional , Humanos , Simulação de Acoplamento Molecular , Transdução de Sinais
11.
Oncology ; 99(9): 555-561, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34247166

RESUMO

INTRODUCTION: Immune checkpoint inhibitors (ICI) are the new standard therapy in patients with metastatic NSCLC (mNSCLC). Metformin, previously associated with improved chemotherapy efficacy in diabetic and nondiabetic cancer patients, was recently associated with increased ICI efficacy. In this study, we aimed to explore the correlations between diabetes mellitus (DM), metformin use, and benefit from ICI in mNSCLC patients. METHODS: All mNSCLC patients treated with ICI in our center between February 2015 and April 2018 were identified. Demographic and clinical data were extracted retrospectively. Cox proportional hazards regression, t tests, and χ2 tests were employed to evaluate associations of progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and disease control rate (DCR), with DM status, metformin use, and HbA1c levels, as appropriate. RESULTS: Of 249 mNSCLC patients treated with ICI, 57 (22.8%) had DM. Thirty-seven (64.9% of all diabetic patients) patients were treated with metformin. A significant negative correlation of DM with PFS and OS was demonstrated (HR 1.5 [1.01-2.06], p = 0.011, and HR 1.5 [1.08-2.08], p = 0.017, respectively). Metformin exposure had no significant correlation with PFS or OS in diabetic mNSCLC patients (HR 1.08 [0.61-1.93], p = 0.79, and HR 1.29 [0.69-2.39], p = 0.42, respectively). There were no differences between groups with respect to ORR and DCR. CONCLUSION: Our data show a potential negative relationship between DM and ICI efficacy in mNSCLC patients. In contrast to reports with chemotherapy, we found no positive relationship between metformin use and ICI therapy in diabetic patients with mNSCLC. Further studies are needed to evaluate the effect of metformin in nondiabetic mNSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/complicações , Complicações do Diabetes , Humanos , Hipoglicemiantes/uso terapêutico , Neoplasias Pulmonares/complicações , Metformina/uso terapêutico , Intervalo Livre de Progressão , Estudos Retrospectivos
12.
N Engl J Med ; 385(5): 416-426, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34320286

RESUMO

BACKGROUND: The prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to adulthood. METHODS: We previously conducted a multicenter clinical trial (from 2004 to 2011) to evaluate the effects of one of three treatments (metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention) on the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. After completion of the trial, participants were transitioned to metformin with or without insulin and were enrolled in an observational follow-up study (performed from 2011 to 2020), which was conducted in two phases; the results of this follow-up study are reported here. Assessments for diabetic kidney disease, hypertension, dyslipidemia, and nerve disease were performed annually, and assessments for retinal disease were performed twice. Complications related to diabetes identified outside the study were confirmed and adjudicated. RESULTS: At the end of the second phase of the follow-up study (January 2020), the mean (±SD) age of the 500 participants who were included in the analyses was 26.4±2.8 years, and the mean time since the diagnosis of diabetes was 13.3±1.8 years. The cumulative incidence of hypertension was 67.5%, the incidence of dyslipidemia was 51.6%, the incidence of diabetic kidney disease was 54.8%, and the incidence of nerve disease was 32.4%. The prevalence of retinal disease, including more advanced stages, was 13.7% in the period from 2010 to 2011 and 51.0% in the period from 2017 to 2018. At least one complication occurred in 60.1% of the participants, and at least two complications occurred in 28.4%. Risk factors for the development of complications included minority race or ethnic group, hyperglycemia, hypertension, and dyslipidemia. No adverse events were recorded during follow-up. CONCLUSIONS: Among participants who had onset of type 2 diabetes in youth, the risk of complications, including microvascular complications, increased steadily over time and affected most participants by the time of young adulthood. Complications were more common among participants of minority race and ethnic group and among those with hyperglycemia, hypertension, and dyslipidemia. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov numbers, NCT01364350 and NCT02310724.).


Assuntos
Complicações do Diabetes/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Adolescente , Criança , Complicações do Diabetes/etnologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dislipidemias/complicações , Dislipidemias/epidemiologia , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Hipoglicemiantes/uso terapêutico , Masculino , Metformina/uso terapêutico , Fatores de Risco
13.
J Cancer Res Clin Oncol ; 147(10): 2819-2836, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34264392

RESUMO

PURPOSE: To assess the effects of metformin use on lung cancer (LC) survival according to summarized results from observational studies (OBs) and randomized clinical trials (RCTs). METHODS: We systematically searched electronic databases and, to our knowledge, for the first time, RCTs were included in a systematic review and meta-analysis about the role of metformin on LC survival. We carried out meta-analyses separately for OBs and RCTs. Analyses for overall survival (OS) concerning OBs were stratified by studies with and without time-dependent approach. Subgroup analyses were adopted for OBs to identify the sources of heterogeneity. Included studies were assessed for quality. RESULTS: We identified ten OBs and four RCTs. For OBs, metformin use was associated with improved OS for LC patients. Only two studies used time-dependent approach in which a higher ratio was found when compared to the non-use of the time-dependent analysis in eight studies. OBs were classified as high quality but the risk of bias was "unclear" in eight OBs due to absence of the time-dependent analysis. For RCTs, metformin use was not beneficial for OS and neither for progression-free survival. Heterogeneous quality was found among RCTs. Sources of bias that could alter significantly the results or raise doubts were identified in RCTs. CONCLUSION: Time-dependent analysis should be considered an appropriate strategy for OBs focused on the metformin use for LC patients' survival, and further studies applying this approach are required. More well-designed RCTs are needed to provide consistent results for the association between metformin use and LC survival.


Assuntos
Hipoglicemiantes/uso terapêutico , Neoplasias Pulmonares/mortalidade , Metformina/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Estudos Observacionais como Assunto , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida
14.
Int J Mol Sci ; 22(14)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34299225

RESUMO

COVID-19 infection poses an important clinical therapeutic problem, especially in patients with coexistent diseases such as type 2 diabetes. Potential pathogenetic links between COVID-19 and diabetes include inflammation, effects on glucose homeostasis, haemoglobin deoxygenation, altered immune status and activation of the renin-angiotensin-aldosterone system (RAAS). Moreover, drugs often used in the clinical care of diabetes (dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, metformin and insulin) may influence the course of SARS-CoV-2 infection, so it is very important to verify their effectiveness and safety. This review summarises the new advances in diabetes therapy and COVID-19 and provides clinical recommendations that are essential for medical doctors and for patients suffering from type 2 diabetes.


Assuntos
COVID-19/terapia , Diabetes Mellitus Tipo 2/terapia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/virologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Metformina/uso terapêutico , SARS-CoV-2/isolamento & purificação , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
15.
Zhonghua Fu Chan Ke Za Zhi ; 56(7): 467-473, 2021 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-34304438

RESUMO

Objective: To investigate effects of metformin and rosiglitazone in non-obese polycystic ovary syndrome (PCOS) women with insulin resistance. Methods: Totally 200 non-obese PCOS women with insulin resistance in West China Second Hospital of Sichuan University were enrolled into this study from Sep. 2013 to Jun. 2016, and were randomly divided into two treatment groups: metformin group (1 500 mg/d) and rosiglitazone group (4 mg/d). The treatment lasted for 6 months. Their clinical and biochemical parameters were collected and compared. Results: In both groups, menstrual cycles [metformin group (37±4) days, rosiglitazone group (35±4) days] were shorter after treatment for 6 months (both P<0.01). After treatment for 6 months, body mass index [metformin group (21.6±1.6) kg/m2, rosiglitazone group (21.7±1.7) kg/m2] decreased in both groups (both P<0.01); decreased LH/FSH ratio (metformin group 1.67±0.80, rosiglitazone group 1.70±0.83) was also observed (both P<0.05). After treatment for 6 months, fasting insulin level [metformin group (13.5±5.1) mU/L, rosiglitazone group (12.7±5.6) mU/L] and homeostasis model assessment-insulin resistance index (metformin group 3.0±1.2, rosiglitazone group 2.8±1.2) were decreased in both groups (all P<0.01). Conclusions: For non-obese PCOS insulin resistance patients, screening of anthropometric and metabolic parameters is necessary. For PCOS with insulin resistance, lifestyle plus insulin sensitizers such as metformin could improve their clinical symptoms, correct the biochemical and metabolic dysfunction.


Assuntos
Resistência à Insulina , Metformina , Síndrome do Ovário Policístico , China , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Insulina , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Rosiglitazona
16.
Biomed Pharmacother ; 139: 111662, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243629

RESUMO

Metformin is one of the most prescribed drugs in type II diabetes (T2DM) which has recently found new applications in the prevention and treatment of various illnesses, from metabolic disorders to cardiovascular and age-related diseases. Metformin improves insulin resistance (IR) by modulating metabolic mechanisms and mitochondrial biogenesis. Alternation of microRNAs (miRs) in the treatment of IR-related illnesses has been observed by metformin therapy. MiRs are small non-coding RNAs that play important roles in RNA silencing, targeting the 3'untranslated region (3'UTR) of most mRNAs and inhibiting the translation of related proteins. As a result, their dysregulation is associated with many diseases. Metformin may alter miRs levels in the treatment of various diseases by AMPK-dependent or AMPK-independent mechanisms. Here, we summarized the therapeutic role of metformin by modifying the aberrant expression of miRs as potential biomarkers or therapeutic targets in diseases in which IR plays a key role.


Assuntos
Hipoglicemiantes/uso terapêutico , Resistência à Insulina/genética , Resistência à Insulina/fisiologia , Metformina/farmacologia , Metformina/uso terapêutico , MicroRNAs/genética , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Humanos , Hipoglicemiantes/farmacologia , Insulina/genética
17.
Otol Neurotol ; 42(7): 1081-1085, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34260511

RESUMO

OBJECTIVE: Recent research demonstrates a potential association between metformin use and reduced sporadic vestibular schwannoma (VS) growth in patients undergoing conservative observation. The current study was designed to elucidate the effect of metformin on tumor growth in sporadic VS using volumetric analyses. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary referral center. PATIENTS: Patients with sporadic VS who elected initial conservative treatment with at least two serial magnetic resonance imaging (MRI) scans were included. INTERVENTIONS: Metformin use among patients with observed sporadic VS. MAIN OUTCOME MEASURES: Tumor growth, defined as an increase in volume of at least 20% from the initial MRI. RESULTS: A total of 361 patients were evaluated. Thirty-four patients (9%) had a diagnosis of diabetes at baseline. Nineteen patients (5%) were taking metformin at the time of the initial MRI. Metformin use was not significantly associated with a reduced risk of volumetric tumor growth in a univariable analysis in all patients undergoing observation for VS (hazard ratio [HR] 0.75; 95% confidence intervals [CI] 0.40-1.42; p = 0.38) or within the diabetic subset (HR 0.79; 95% CI 0.34-1.83; p = 0.58). Additionally, diabetes status, insulin dependence, hemoglobin A1c value, and metformin dose were not significantly associated with volumetric tumor growth. CONCLUSION: Despite promising initial results in several previous studies, our data suggest that metformin use does not significantly reduce the risk of volumetric tumor growth in sporadic VS.


Assuntos
Metformina , Neuroma Acústico , Humanos , Imageamento por Ressonância Magnética , Metformina/uso terapêutico , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/tratamento farmacológico , Estudos Retrospectivos , Carga Tumoral
18.
Int J Mol Sci ; 22(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34281285

RESUMO

Sjögren's syndrome (SS), a chronic inflammatory disease involving the salivary and lacrimal glands, presents symptoms of sicca as well as systemic manifestations such as fatigue and musculoskeletal pain. Only a few treatments have been successful in management of SS; thus treatment of the disease is challenging. Metformin is the first-line agent for type 2 diabetes and has anti-inflammatory potential. Its immunomodulatory capacity is exerted via activation of 5' adenosine monophosphate-activated protein kinase (AMPK). Metformin inhibits mitochondrial respiratory chain complex I which leads to change in adenosine mono-phosphate (AMP) to adenosine tri-phosphate (ATP) ratio. This results in AMPK activation and causes inhibition of mammalian target of rapamycin (mTOR). mTOR plays an important role in T cell differentiation and mTOR deficient T cells differentiate into regulatory T cells. In this manner, metformin enhances immunoregulatory response in an individual. mTOR is responsible for B cell proliferation and germinal center (GC) differentiation. Thus, reduction of B cell differentiation into antibody-producing plasma cells occurs via downregulation of mTOR. Due to the lack of suggested treatment for SS, metformin has been considered as a treatment strategy and is expected to ameliorate salivary gland function.


Assuntos
Metformina/uso terapêutico , Síndrome de Sjogren/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Humanos , Fatores Imunológicos/uso terapêutico , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Transdução de Sinais/efeitos dos fármacos , Síndrome de Sjogren/etiologia , Síndrome de Sjogren/fisiopatologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Serina-Treonina Quinases TOR/metabolismo
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