Metformin decreases plasma resistin concentrations in pediatric patients with impaired glucose tolerance: a placebo-controlled randomized clinical trial

Gómez-Díaz, Rita A.; Talavera, Juan O.; Pool, Elsy Canché; Ortiz-Navarrete, Vianney; Solórzano-Santos, Fortino; Mondragón-González, Rafael; Valladares‐Salgado, Adán; Cruz, Miguel; Aguilar-Salinas, Carlos A.; Wacher, Niels H.

doi:10.1016/j.metabol.2012.02.003

Cited by 46 publications

(34 citation statements)

References 45 publications

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“…Similar results were also observed by other studies [21,22]. However, the data from other group revealed that treated patients (MS or type 2 diabetes) with metformin, resistin was not changed or decreased [23,24]. The mean concentration of resistin varied widely.…”

Section: Evaluation Of the Hypothesissupporting

confidence: 88%

Resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin

et al. 2013

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Section: Evaluation Of the Hypothesissupporting

confidence: 88%

Resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin

et al. 2013

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“…Clinical research in this area is revealing effects of metformin not previously characterized in detail, including effects on inflammatory mediators and resistin (42,43). Additional systemic effects of metformin related to reduction in glucagon signaling, attributable to the effects of the drug on ATP production in glucagonresponsive cells, may also be important (44).…”

Section: Mechanisms Of Action Of Potential Relevance To Oncologymentioning

confidence: 99%

Potential applications for biguanides in oncology

2013

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Metformin is widely prescribed for the treatment of type II diabetes. Recently, it has been proposed that this compound or related biguanides may have antineoplastic activity. Biguanides may exploit specific metabolic vulnerabilities of transformed cells by acting on them directly, or may act by indirect mechanisms that involve alterations of the host environment. Preclinical data suggest that drug exposure levels are a key determinant of proposed direct actions. With respect to indirect mechanisms, it will be important to determine whether recently demonstrated metformin-induced changes in levels of candidate systemic mediators such as insulin or inflammatory cytokines are of sufficient magnitude to achieve therapeutic benefit. Results of the first generation of clinical trials now in progress are eagerly anticipated. Ongoing investigations may justify a second generation of trials that explore pharmacokinetic optimization, rational drug combinations, synthetic lethality strategies, novel biguanides, and the use of predictive biomarkers.

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“…When the 7 placebo-controlled trials were con- sidered separately in sensitivity analyses, the WMDs were not meaningfully affected, but the 95% CIs for the overall effect were generally wider for BMI (WMD, −0.5; 95% CI, −1.1 to 0.1; I 2 = 16% and n = 374), height (WMD, 0.7; 95% CI, −0.2 to 1.5 cm; I 2 = 0% and n = 374), and weight (WMD, −0.8; 95% CI, −3.4 to 1.8 kg; I 2 = 75% and n = 308). [5][6][7][8]18,19,21 Sensitivity analyses revealed similar results when the analyses were performed after lowering the age limit to 14 years or increasing the minimum study duration to 6 months. The funnel plots (eFigure 2 in the Supplement) did not suggest publication bias.…”

Section: Resultsmentioning

confidence: 93%

“…One study 15 of type 2 diabetes mellitus met our inclusion criteria but was excluded because 65% of the participants taking the placebo required rescue medication before the 16-week measurements. Height was available from only 10 studies (6 studies 5,6,[16][17][18][19] provided the data in the articles, 1 study 8 listed the data from a repository, and the data from 3 studies 17,20,21 were obtained after we contacted the authors). These 10 studies included a total of 562 children and adolescents at baseline and 477 of these with changes to data.…”

Section: Resultsmentioning

confidence: 99%

Evaluating the Effects of Metformin Use on Height in Children and Adolescents

et al. 2015

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IMPORTANCE Metformin hydrochloride use is increasing in children and adolescents. Previous meta-analyses have identified a large variability in the effects of metformin use on body mass index changes but have not considered height changes as a confounder, to our knowledge.OBJECTIVE To conduct a systematic review and meta-analysis of the effects of metformin use on height in children and adolescents.DATA SOURCES Computerized databases, including MEDLINE and EMBASE, were searched up to September 9, 2014, for terms related to metformin and childhood or adolescence.STUDY SELECTION Randomized clinical trials examining the effects of metformin use on height of participants younger than 19 years were considered eligible. Trials with cointerventions other than lifestyle changes were excluded.DATA EXTRACTION AND SYNTHESIS Height, weight, body mass index, age, sex, metformin dosage, and study duration were independently extracted by 2 reviewers. The weighted mean differences for changes in height, weight, and body mass index were compared between the metformin and control groups using random-effects models. MAIN OUTCOME AND MEASURE Height changes.RESULTS Ten studies were included, with a total of 562 participants, 330 (58.7%) of whom were female. The mean age within the studies ranged from 7.9 to 16.1 years, with a high variability in most studies. The duration of metformin interventions lasted from 3 to 48 months. Overall, height changes were not significantly different between the metformin and control groups. However, stratified analyses according to the cumulative metformin dose (in milligrams per day times the number of days of treatment) showed a greater increase in height with metformin use in the 5 studies providing the largest cumulative metformin doses (weighted mean difference, 1.0; 95% CI, 0.0 to 2.0 cm) but not in the 5 studies providing the lowest doses (weighted mean difference, −0.1; 95% CI, −0.7 to 1.0 cm) compared with the control group. CONCLUSIONS AND RELEVANCEPreliminary evidence suggests a dose-response relationship between metformin use and increases in height in children and adolescents compared with a control group. While an approximate 1-cm increase in height may appear small, it is likely underestimated given that many studies were of short duration and included older adolescents, potentially after epiphyseal growth plate closure.

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Metformin decreases plasma resistin concentrations in pediatric patients with impaired glucose tolerance: a placebo-controlled randomized clinical trial

Cited by 46 publications

References 45 publications

Resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin

Resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin

Potential applications for biguanides in oncology

Evaluating the Effects of Metformin Use on Height in Children and Adolescents

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