The Effect of Eighteen-Month Metformin Treatment in Obese Adolescents: Comparison of Results Obtained in Daily Practice with Results from a Clinical Trial

Aa, Marloes P van der; Hoving, Vera; Garde, E.M.W. van de; Boer, Anthonius de; Knibbe, Catherijne A. J.; Vorst, Marja M J van der

doi:10.1155/2016/7852648

Cited by 10 publications

(6 citation statements)

References 15 publications

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“…As biguanides carry a positive charge, we hypothesize that the increased mitochondrial density in beige iWAT allows the accumulation of these moieties at higher levels than in white iWAT from control mice [36]. Moreover, metformin's activation of HSL at serine 660 in control animals lends further credence to the ability of this drug to suppress obesity in a healthy state [37]. Interestingly, burn alone or metformin treatment did not alter blood glucose levels.…”

Section: Discussionmentioning

confidence: 92%

Metformin prevents the pathological browning of subcutaneous white adipose tissue

Auger

Knuth

Abdullahi

et al. 2019

Molecular Metabolism

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Objective Browning, the conversion of white adipose tissue (WAT) to a beige phenotype, has gained interest as a strategy to induce weight loss and improve insulin resistance in metabolic disorders. However, for hypermetabolic conditions stemming from burn trauma or cancer cachexia, browning is thought to contribute to energy wasting and supraphysiological nutritional requirements. Metformin's impact on this phenomenon and underlying mechanisms have not been explored. Methods We used both a murine burn model and human ex vivo adipose explants to assess metformin and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR)'s effects on the development of subcutaneous beige adipose. Enzymes involved in fat homeostasis and browning, as well as mitochondrial dynamics, were assessed to determine metformin's effects. Results Treatment with the biguanide metformin lowers lipolysis in beige fat by inducing protein phosphatase 2A (PP2A) independently of adenosine monophosphate kinase (AMPK) activation. Increased PP2A activity catalyzes the dephosphorylation of acetyl-CoA carboxylase (Ser 79) and hormone sensitive lipase (Ser 660), thus promoting fat storage and the “whitening” of otherwise lipolytic beige adipocytes. Moreover, co-incubation of metformin with the PP2A inhibitor okadaic acid countered the anti-lipolytic effects of this biguanide in human adipose. Additionally, we show that metformin does not activate this pathway in the WAT of control mice and that AICAR sustains the browning of white adipose, offering further evidence that metformin acts independently of this cellular energy sensor. Conclusions This work provides novel insights into the mechanistic underpinnings of metformin's therapeutic benefits and potential as an agent to reduce the lipotoxicity associated with hypermetabolism and adipose browning.

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Section: Discussionmentioning

confidence: 92%

Metformin prevents the pathological browning of subcutaneous white adipose tissue

Auger

Knuth

Abdullahi

et al. 2019

Molecular Metabolism

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“…This finding was also consistent with the results of studies in other single populations. 4,[43][44][45][46] A dose comparison considering the weight loss effect of metformin in obese women with PCOS demonstrated that substantial weight reduction is potentially achievable with high doses of metformin. 47 This result is consistent with the current subgroup analysis.…”

Section: Discussionmentioning

confidence: 99%

Effects of metformin in obesity treatment in different populations: a meta-analysis

Shi

Gan

et al. 2020

Therapeutic Advances in Endocrinology

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Objective: Some studies have shown that metformin can reduce body weight. However, metformin has not been officially approved as a medicine for weight loss because its effect on different populations remains inconsistent. This meta-analysis aimed to summarize the weight loss effect of metformin quantitatively. Method: The randomized controlled and high-quality case-control trials of metformin monotherapy in obesity treatment were eligible. Baseline body mass index (BMI) was chosen as a self-control to compare the changes in BMI of different populations before and after treatment. All changes were calculated as differences between the final and initial BMI values (with negative values indicating a decrease). Results were presented as weighted mean difference (WMD) with a 95% confidence interval (CI 95%). Subgroup analysis was performed based on baseline BMI, age, daily dose, and duration of medication. Results: A total of 21 trials ( n = 1004) were included, and the meta-analysis of metformin treatment in different populations showed that metformin has a modest reduction in the BMI of included participants (WMD −0.98; 95% CI, −1.25 to −0.72), and the reduction of BMI was most significant in the simple obesity population (WMD −1.31; 95% CI, −2.07 to −0.54). The subgroup analysis showed that metformin treatment significantly reduced BMI in obesity patients with a BMI >35kg/m2 (WMD −1.12; 95% CI, −1.84 to −0.39) compared with before treatment. BMI in the high dose group decreased by 1.01 units (WMD−1.01; 95% CI, −1.29 to −0.73) and BMI did not continue to decrease significantly after treatment of more than 6 months. Conclusion: Patients treated with metformin experienced about a one-unit reduction in BMI at the end of treatment. But whether this decreased value produced enough weight loss (5% of baseline body weight) to qualify as a “weight loss drug” as current guidelines require, requires larger specific randomized control trials.

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“…Metformin is the first-line antidiabetic agent which is primarily used for the treatment of type II diabetes mellitus because of its efficacy and tolerability [16, 17]. In addition, recent studies have shown its anticancer [18–20], antitubercular [21, 22], antioxidant properties [23–25], and neuroprotective [26] actions.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Metformin in Experimentally Induced Animal Models of Epileptic Seizure

Yimer

Surur

Wondafrash

et al. 2019

Behavioural Neurology

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Background. Epilepsy is one of the common neurological illnesses which affects millions of individuals globally. Although the majority of epileptic patients have a good response for the currently available antiepileptic drugs (AEDs), about 30-40% of epileptic patients are developing resistance. In addition to low safety profiles of most of existing AEDs, there is no AED available for curative or disease-modifying actions for epilepsy so far. Objectives. This systematic review is intended to evaluate the effect of metformin in acute and chronic animal models of an epileptic seizure. Methods. We searched PubMed, SCOPUS, Sciences Direct, and grey literature in order to explore articles published in English from January 2010 to November 2018, using key terms “epilepsy,” “seizure,” “metformin,” “oral hypoglycemic agents,” and “oral antidiabetic drugs”. The qualities of all the included articles were assessed according to the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES). Results. Out of six hundred fifty original articles retrieved, eleven of them fulfilled the inclusion criteria and were included for final qualitative analysis. In these studies, metformin showed to control seizure attacks by attenuating seizure generation, delaying the onset of epilepsy, reducing hippocampal neuronal loss, and averting cognitive impairments in both acute and chronic models of an epileptic seizure. The possible mechanisms for its antiseizure or antiepileptic action might be due to activation of AMPK, antiapoptotic, antineuroinflammatory, and antioxidant properties, which possibly modify disease progression through affecting epileptogenesis. Conclusion. This review revealed the benefits of metformin in alleviating symptoms of epileptic seizure and modifying different cellular and molecular changes that affect the natural history of the disease in addition to its good safety profile.

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The Effect of Eighteen-Month Metformin Treatment in Obese Adolescents: Comparison of Results Obtained in Daily Practice with Results from a Clinical Trial

Cited by 10 publications

References 15 publications

Metformin prevents the pathological browning of subcutaneous white adipose tissue

Metformin prevents the pathological browning of subcutaneous white adipose tissue

Effects of metformin in obesity treatment in different populations: a meta-analysis

The Effect of Metformin in Experimentally Induced Animal Models of Epileptic Seizure

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