The influence of metformin on IGF-1 levels in humans: A systematic review and meta-analysis

Xiaodong Yang; Hamed Kord-Varkaneh; Sam Talaei; Cain C.T. Clark; Fernando Zanghelini; Shing Cheng Tan; Meysam Zarezadeh; Seyed Mohammad Mousavi; Jamal Rahmani; Yong Zhang

doi:10.1016/j.phrs.2019.104588

The influence of metformin on IGF-1 levels in humans: A systematic review and meta-analysis

Xiaodong Yang, Hamed Kord-Varkaneh, Sam Talaei, Cain C.T. Clark, Fernando Zanghelini, Shing Cheng Tan, Meysam Zarezadeh, Seyed Mohammad Mousavi, Jamal Rahmani, Yong Zhang

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Abstract

Background: A meta-analysis is needed to comprehensively consolidate findings from the influence of metformin on IGF-1 levels. The present study was conducted with the objective to accurately evaluate the influence of metformin intake on IGF-1 levels via a meta-analysis of randomized controlled trials. Methods: A comprehensive systematic search was carried out in PubMed/MEDLINE, Web of Science, SCOPUS and Embase from inception until June 2019. Weighted mean difference (WMD) with the 95 % CI were applied for estimating the effects of metformin on serum IGF-1 levels. Results: 11 studies involving a total of 569 individuals reported changes in IGF-1 plasma concentrations as an outcome measure. Pooled results demonstrated an overall non-significant decline in IGF-1 following metformin intake (WMD: -8.292 ng/ml, 95 % CI: -20.248, 3.664, p = 0.174) with heterogeneity among (p = 0.000,I² = 87.1 %). The subgroup analyses displayed that intervention duration <12 weeks on children (WMD:-55.402 ng/ml, 95 % CI: -79.845, -30.960, I2 = 0.0 %) significantly reduced IGF-1. Moreover, in age 18 < years older metformin intake (WMD: 15.125 ng/ml, 95 % CI: 5.522, 24.729, I2 = 92.5 %) significantly increased IGF-1 than 18 ≤ years older (WMD:-1.038 ng/ml, 95 % CI: -3.578,1.502,I² = 78.0 %). Following dose-response evaluation, metformin intake reduced IGF-1 (coefficient for dose-response analysis= -13.14, P = 0.041 and coefficient for liner analysis= -0.066, P = 0.038) significantly based on treatment duration. Conclusion: We found in children, intervention duration <12 weeks yielded significant reductions in IGF-1, whilst paradoxically, in participants >18 years old, metformin intake significantly increased IGF-1. We suggest that caution be taken when interpreting the findings of this review, particularly given the discordant supplementation practices between children and adults.

Original language	English
Article number	104588
Journal	Pharmacological Research
Volume	151
Early online date	6 Dec 2019
DOIs	https://doi.org/10.1016/j.phrs.2019.104588
Publication status	Published - 1 Jan 2020

Bibliographical note

NOTICE: this is the author’s version of a work that was accepted for publication in Pharmacological Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Pharmacological Research, 151, (2020) DOI: 10.1016/j.phrs.2019.104588

© 2020, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

Biguanidine
IGF-1
Insulin-like growth factor I
Meta-analysis
Metformin

ASJC Scopus subject areas

Pharmacology

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10.1016/j.phrs.2019.104588

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Cite this

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title = "The influence of metformin on IGF-1 levels in humans: A systematic review and meta-analysis",

abstract = "Background: A meta-analysis is needed to comprehensively consolidate findings from the influence of metformin on IGF-1 levels. The present study was conducted with the objective to accurately evaluate the influence of metformin intake on IGF-1 levels via a meta-analysis of randomized controlled trials. Methods: A comprehensive systematic search was carried out in PubMed/MEDLINE, Web of Science, SCOPUS and Embase from inception until June 2019. Weighted mean difference (WMD) with the 95 % CI were applied for estimating the effects of metformin on serum IGF-1 levels. Results: 11 studies involving a total of 569 individuals reported changes in IGF-1 plasma concentrations as an outcome measure. Pooled results demonstrated an overall non-significant decline in IGF-1 following metformin intake (WMD: -8.292 ng/ml, 95 % CI: -20.248, 3.664, p = 0.174) with heterogeneity among (p = 0.000,I2 = 87.1 %). The subgroup analyses displayed that intervention duration <12 weeks on children (WMD:-55.402 ng/ml, 95 % CI: -79.845, -30.960, I2 = 0.0 %) significantly reduced IGF-1. Moreover, in age 18 < years older metformin intake (WMD: 15.125 ng/ml, 95 % CI: 5.522, 24.729, I2 = 92.5 %) significantly increased IGF-1 than 18 ≤ years older (WMD:-1.038 ng/ml, 95 % CI: -3.578,1.502,I2 = 78.0 %). Following dose-response evaluation, metformin intake reduced IGF-1 (coefficient for dose-response analysis= -13.14, P = 0.041 and coefficient for liner analysis= -0.066, P = 0.038) significantly based on treatment duration. Conclusion: We found in children, intervention duration <12 weeks yielded significant reductions in IGF-1, whilst paradoxically, in participants >18 years old, metformin intake significantly increased IGF-1. We suggest that caution be taken when interpreting the findings of this review, particularly given the discordant supplementation practices between children and adults.",

keywords = "Biguanidine, IGF-1, Insulin-like growth factor I, Meta-analysis, Metformin",

author = "Xiaodong Yang and Hamed Kord-Varkaneh and Sam Talaei and Clark, {Cain C.T.} and Fernando Zanghelini and Tan, {Shing Cheng} and Meysam Zarezadeh and Mousavi, {Seyed Mohammad} and Jamal Rahmani and Yong Zhang",

note = "NOTICE: this is the author{\textquoteright}s version of a work that was accepted for publication in Pharmacological Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Pharmacological Research, 151, (2020) DOI: 10.1016/j.phrs.2019.104588 {\textcopyright} 2020, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ ",

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doi = "10.1016/j.phrs.2019.104588",

language = "English",

volume = "151",

journal = "Pharmacological Research",

issn = "1043-6618",

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TY - JOUR

T1 - The influence of metformin on IGF-1 levels in humans

T2 - A systematic review and meta-analysis

AU - Yang, Xiaodong

AU - Kord-Varkaneh, Hamed

AU - Talaei, Sam

AU - Clark, Cain C.T.

AU - Zanghelini, Fernando

AU - Tan, Shing Cheng

AU - Zarezadeh, Meysam

AU - Mousavi, Seyed Mohammad

AU - Rahmani, Jamal

AU - Zhang, Yong

N1 - NOTICE: this is the author’s version of a work that was accepted for publication in Pharmacological Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Pharmacological Research, 151, (2020) DOI: 10.1016/j.phrs.2019.104588 © 2020, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Background: A meta-analysis is needed to comprehensively consolidate findings from the influence of metformin on IGF-1 levels. The present study was conducted with the objective to accurately evaluate the influence of metformin intake on IGF-1 levels via a meta-analysis of randomized controlled trials. Methods: A comprehensive systematic search was carried out in PubMed/MEDLINE, Web of Science, SCOPUS and Embase from inception until June 2019. Weighted mean difference (WMD) with the 95 % CI were applied for estimating the effects of metformin on serum IGF-1 levels. Results: 11 studies involving a total of 569 individuals reported changes in IGF-1 plasma concentrations as an outcome measure. Pooled results demonstrated an overall non-significant decline in IGF-1 following metformin intake (WMD: -8.292 ng/ml, 95 % CI: -20.248, 3.664, p = 0.174) with heterogeneity among (p = 0.000,I2 = 87.1 %). The subgroup analyses displayed that intervention duration <12 weeks on children (WMD:-55.402 ng/ml, 95 % CI: -79.845, -30.960, I2 = 0.0 %) significantly reduced IGF-1. Moreover, in age 18 < years older metformin intake (WMD: 15.125 ng/ml, 95 % CI: 5.522, 24.729, I2 = 92.5 %) significantly increased IGF-1 than 18 ≤ years older (WMD:-1.038 ng/ml, 95 % CI: -3.578,1.502,I2 = 78.0 %). Following dose-response evaluation, metformin intake reduced IGF-1 (coefficient for dose-response analysis= -13.14, P = 0.041 and coefficient for liner analysis= -0.066, P = 0.038) significantly based on treatment duration. Conclusion: We found in children, intervention duration <12 weeks yielded significant reductions in IGF-1, whilst paradoxically, in participants >18 years old, metformin intake significantly increased IGF-1. We suggest that caution be taken when interpreting the findings of this review, particularly given the discordant supplementation practices between children and adults.

AB - Background: A meta-analysis is needed to comprehensively consolidate findings from the influence of metformin on IGF-1 levels. The present study was conducted with the objective to accurately evaluate the influence of metformin intake on IGF-1 levels via a meta-analysis of randomized controlled trials. Methods: A comprehensive systematic search was carried out in PubMed/MEDLINE, Web of Science, SCOPUS and Embase from inception until June 2019. Weighted mean difference (WMD) with the 95 % CI were applied for estimating the effects of metformin on serum IGF-1 levels. Results: 11 studies involving a total of 569 individuals reported changes in IGF-1 plasma concentrations as an outcome measure. Pooled results demonstrated an overall non-significant decline in IGF-1 following metformin intake (WMD: -8.292 ng/ml, 95 % CI: -20.248, 3.664, p = 0.174) with heterogeneity among (p = 0.000,I2 = 87.1 %). The subgroup analyses displayed that intervention duration <12 weeks on children (WMD:-55.402 ng/ml, 95 % CI: -79.845, -30.960, I2 = 0.0 %) significantly reduced IGF-1. Moreover, in age 18 < years older metformin intake (WMD: 15.125 ng/ml, 95 % CI: 5.522, 24.729, I2 = 92.5 %) significantly increased IGF-1 than 18 ≤ years older (WMD:-1.038 ng/ml, 95 % CI: -3.578,1.502,I2 = 78.0 %). Following dose-response evaluation, metformin intake reduced IGF-1 (coefficient for dose-response analysis= -13.14, P = 0.041 and coefficient for liner analysis= -0.066, P = 0.038) significantly based on treatment duration. Conclusion: We found in children, intervention duration <12 weeks yielded significant reductions in IGF-1, whilst paradoxically, in participants >18 years old, metformin intake significantly increased IGF-1. We suggest that caution be taken when interpreting the findings of this review, particularly given the discordant supplementation practices between children and adults.

KW - Biguanidine

KW - IGF-1

KW - Insulin-like growth factor I

KW - Meta-analysis

KW - Metformin

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U2 - 10.1016/j.phrs.2019.104588

DO - 10.1016/j.phrs.2019.104588

M3 - Review article

C2 - 31816435

AN - SCOPUS:85077317179

SN - 1043-6618

VL - 151

JO - Pharmacological Research

JF - Pharmacological Research

M1 - 104588

ER -

The influence of metformin on IGF-1 levels in humans: A systematic review and meta-analysis

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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