Metformin influences on respiratory system in obese mice induced by postnatal overnutrition

Dias, Maycon Daniel; Goulart, Melissa; Dalécio, Cecilia; Enes-Marques, Silvia; Salles, Évila da Silva Lopes; Venâncio, Marina; Pereira, Elisângela Monteiro; Paffaro, Valdemar A.; Incerpi, Erika K.; Soncini, Roseli

doi:10.1016/j.resp.2017.09.010

Cited by 6 publications

(7 citation statements)

References 40 publications

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“…also showed that there were no effects on NOx and that metformin did not resolve bronchoconstriction in obese mice (31). More studies are needed to delineate the effects of metformin on inflammation.…”

Section: Summary Of Main Findingsmentioning

confidence: 99%

Role of metformin in treatment of patients with chronic obstructive pulmonary disease: a systematic review

Zhu¹,

Teng²,

Ge³

et al. 2019

J. Thorac. Dis.

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Chronic obstructive pulmonary disease (COPD) is commonly associated with type 2 diabetes mellitus (T2DM). Metformin is a first-line treatment for most patients with T2DM, and may have antiaging, antioxidant, and anti-tumour effects. A few published studies report the use of metformin for the treatment of COPD in patients with or without T2DM, but the results are inconsistent. This study aimed to confirm the effectiveness and safety of metformin as a treatment option in patients with COPD. We performed a systematic search of PubMed, EMBASE, and the Cochrane database from their starting date to December 2017. Randomised controlled trials (RCTs), controlled clinical trials, and retrospective researches reporting the use of metformin for treating patients with COPD were identified. We included a total of six articles (involving 3,467 participants) and found that metformin may benefit patients with COPD and T2DM by improving health status and symptoms, hospitalisations, and mortality. There was no effect on patients with COPD without T2DM. Metformin causes minimal increases in plasma lactate concentrations without lactic acidosis and has little impact on blood glucose and minor adverse events. Metformin is safe and effective for treating COPD in patients with concomitant T2DM.

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Section: Summary Of Main Findingsmentioning

confidence: 99%

Role of metformin in treatment of patients with chronic obstructive pulmonary disease: a systematic review

Zhu¹,

Teng²,

Ge³

et al. 2019

J. Thorac. Dis.

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“…During the last 14 days of the experiment, metformin group was treated with metformin added in drinking water with a target dose of 300 mg/kg/day. The dose of metformin and the time course were chosen based on the previous studies (Shore et al, 2008;Dias et al, 2018). Metformin hydrochloride (PeproTech, NJ) was dissolved 3.375 g/L in drinking water, calculated based on the average body weight of mice and an estimated water consumption of 4 ml/mouse/day as Dias et al (Dias et al, 2018).…”

Section: Animals and Study Designmentioning

confidence: 99%

“…The dose of metformin and the time course were chosen based on the previous studies (Shore et al, 2008;Dias et al, 2018). Metformin hydrochloride (PeproTech, NJ) was dissolved 3.375 g/L in drinking water, calculated based on the average body weight of mice and an estimated water consumption of 4 ml/mouse/day as Dias et al (Dias et al, 2018). Control group was drinking water without metformin.…”

Section: Animals and Study Designmentioning

confidence: 99%

“…Metformin was shown to reduce airway inflammation and remodeling in allergic murine asthma models (Park et al, 2012;Calixto et al, 2013;Guo et al, 2021). By contrast, metformin did not affect AHR in studies of db/db mice or obese Swiss mice induced by overfeeding (Shore et al, 2008;Dias et al, 2018). Effects of metformin on airway hyperresponsiveness or inflammation in DIO mice in the absence of allergic sensitization have not been examined.…”

Section: Introductionmentioning

confidence: 99%

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Metformin Alleviates Airway Hyperresponsiveness in a Mouse Model of Diet-Induced Obesity

Loube

Lee

et al. 2022

Front. Physiol.

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Obese asthma is a unique phenotype of asthma characterized by non-allergic airway hyperresponsiveness (AHR) and inflammation which responds poorly to standard asthma therapy. Metformin is an oral hypoglycemic drug with insulin-sensitizing and anti-inflammatory properties. The objective of the current study was to test the effect of metformin on AHR in a mouse model of diet-induced obesity (DIO). We fed 12-week-old C57BL/6J DIO mice with a high fat diet for 8 weeks and treated them with either placebo (control, n = 10) or metformin (n = 10) added in drinking water (300 mg/kg/day) during the last 2 weeks of the experiment. We assessed AHR, metabolic profiles, and inflammatory markers after treatments. Metformin did not affect body weight or fasting blood glucose, but significantly reduced serum insulin (p = 0.0117). Metformin reduced AHR at 30 mg/ml of methacholine challenge (p = 0.0052) without affecting baseline airway resistance. Metformin did not affect circulating white blood cell counts or lung cytokine mRNA expression, but modestly decreased circulating platelet count. We conclude that metformin alleviated AHR in DIO mice. This finding suggests metformin has the potential to become an adjuvant pharmacological therapy in obese asthma.

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“…LPS-induced bronchial epithelial cell injury could be ameliorated by metformin via NF-κB signaling suppression [35]. Metformin induced decreases in the VEGFa level in the airway in obese mice to alleviate airway remodeling [36]. ese examples may be mechanisms by which metformin interferes with asthma.…”

Section: Study or Subgroup LI 2016 Wu 2019mentioning

confidence: 99%

Association of Metformin Use with Asthma Exacerbation in Patients with Concurrent Asthma and Diabetes: A Systematic Review and Meta-Analysis of Observational Studies

Wen

Wang

Chai

et al. 2020

Canadian Respiratory Journal

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Background. Asthma and diabetes are both diseases that affect a wide range of people worldwide. As a common treatment for diabetes, metformin has also been reported to be effective in improving asthma outcomes. We conducted a combined analysis to examine the efficacy of metformin in reducing asthma exacerbation in patients with concurrent asthma and diabetes. Methods. We searched the PubMed, Embase, and CENTRAL databases for articles published prior to April 2020 to find observational studies of individuals with concurrent asthma and diabetes that compared the risk of asthma exacerbation between metformin users and nonusers. Two researchers separately screened the studies, extracted data, and evaluated the risk of bias. The primary outcome was the adjusted risk of asthma exacerbation. The secondary outcomes were the adjusted risk of asthma-related hospitalization and emergency room visits. Review Manager was used for data analysis and plotting. I2 and χ2 tests were used to estimate heterogeneity. A random effects or fixed effects model was used depending on the heterogeneity. Odds ratios were calculated for dichotomous variables. Results. We included two studies with a total of 25252 patients. The pooled effect size showed that metformin was inversely associated with a risk of asthma exacerbation (OR = 0.65, 95% CI 0.28–1.48; χ2 = 5.42, P=0.02; I2 = 82%), asthma-related emergency department visits (OR = 0.81, 95% CI 0.74–0.89; χ2 = 0.36, P=0.55; I2 = 0%), and hospitalizations (OR = 0.43, 95% CI 0.14–1.29; χ2 = 4.01, P=0.05; I2 = 75%). Conclusion. This meta-analysis suggested that metformin decreased the risk of asthma-related emergency room visits for patients with concurrent asthma and diabetes. Metformin reduced the risk of asthma-related hospitalization and exacerbation but was not statistically significant. More randomized trials involving larger samples should be considered, and the mechanisms of these effects need to be fully elucidated.

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Metformin influences on respiratory system in obese mice induced by postnatal overnutrition

Cited by 6 publications

References 40 publications

Role of metformin in treatment of patients with chronic obstructive pulmonary disease: a systematic review

Role of metformin in treatment of patients with chronic obstructive pulmonary disease: a systematic review

Metformin Alleviates Airway Hyperresponsiveness in a Mouse Model of Diet-Induced Obesity

Association of Metformin Use with Asthma Exacerbation in Patients with Concurrent Asthma and Diabetes: A Systematic Review and Meta-Analysis of Observational Studies

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