»frontiers
`REVIEW
`published: 28 November 2018
`in Pharmacology
`doi: 10.3389/fphar.201 8.01393
`
`®Check for
`updates
`
`Topiramate and Metformin Are
`Effective Add-On Treatmentsin
`Controlling Antipsychotic-Induced
`Weight Gain: A Systematic Review
`and Network Meta-Analysis
`
`Chuanjun Zhuo'445.*t, Yong Xu+56t, Sha Liu+**t, Jing Li***, Qishi Zheng’,
`Xiangyang Gao’, ShenLi*, Rixing Jing®, Xueqin Song”, Weihua Yue".*,
`Chunhua Zhou** and Rachel Upthegrove™5
`
`' Departmentof Psychiatry and Morbidity, Tianjin Anding Hospital, Tianjin Medical University, Tianjin, China, ? Department
`of Psychiatry, Jining Medical University, Jining, China, * Department of Psychiatry, Tianjin Medical University, Tianjin, China,
`* Departmentof Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China, § MDT
`Center for Cognitive Impairment and Sleep Disorders, First Hospital of Shanxi Medical University, Taiyuan, China,
`® Departmentof Neurobiology, National Key Disciplines, Key Laboratory for Cellular Physiology of Ministry of Education,
`Shanxi Medical University, Taiyuan, China, ’ Department of Epidemiology, Singapore Clinical Research Institute, Singapore,
`Singapore, * Health Management Institute, Big Data Analysis Center, Chinese PLA General Hospital, Beijing, China,
`° Departmentof Pattern Recognition, China National Key Laboratory, Institute of Automation, Chinese Academyof Sciences,
`Beijing, China, ® Departmentof Psychiatry, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, '’ Peking
`University Sixth Hospital, Institute of Mental Health, Beijing, China, ** Key Laboratory of Mental Health, Ministry of Health &
`National Clinical Research Center for Mental Disorders, Peking University, Beijing, China, ® Department ofPharmacy, Hebei
`Medical University First Hospital, Shijiazhuang, China, “ Institute for Mental Health, University of Birmingham, Birmingham,
`United Kingdom,"* Early Intervention Service, Forward Thinking Birmingham, Birmingham, United Kingdom
`
`Background: Antipsychotic drugs may lead to side effects such as obesity, diabetes,
`dyslipidemia, and cardiovascular disease. The current systematic review and network
`meta-analysis analyzes and provides an update on the clinical performance of these
`add-ons in comparison to placebo on body weight and body mass index (BMI)
`reductions.
`
`Methods: A comprehensiveliterature search was performed on electronic databases:
`PubMed (1946-), Embase (1974-), Cochranelibrary (1992-), and OpenGrey (2000-)
`until 31 July 2018. Network meta-analyses, comparing the body weight change, BMI
`change and withdrawndue to adverse eventsofdifferent pharmacological add-ons, was
`performed using a multivariate meta-regression model with random-effects, adopting a
`frequentist approach. To rank the prognosis for all add-ons, we used surface under the
`cumulative ranking (GUCRA) values.
`
`Outcomes: From 614 potential studies identified, 27 eligible studies (n = 1,349 subjects)
`were included. All the studies demonstrated low to moderate risk of bias. For the
`
`analysis of body weight change,all add-ons except Ranitidine showedsignificant weight
`
`OPEN ACCESS
`
`Edited by:
`Tahir Mehmood Khan,
`University of Veterinary and Animal
`Sciences, Pakistan
`
`Reviewed by:
`Marc Henri De Longueville,
`UCB Pharma, Belgium
`Kurt Neumann,
`Independent Researcher, Kerékteleki,
`Hungary
`
`*Correspondence:
`Chunhua Zhou
`zhouchunhua80@126.com
`Chuanjun Zhuo
`Chuanjunzhuotimh@163.com;
`Chuanjunzhuotimh@ieee.org
`Weihua Yue
`Oryue@bjmu.edu.cn
`These authors have contributed
`equally to this work
`
`Specialty section:
`This article was submitted to
`Pharmaceutical Medicine
`and Outcomes Research,
`a section of the joumal
`Frontiers in Pharmacology
`
`Received: 19 September 2018
`Accepted: 12 November 2018
`Published: 28 November 2018
`
`Citation:
`Zhuo C, Xu Y, Liu S, Li J,
`Zheng Q, Gao X, Li S, Jing R, Song X,
`Yue W, Zhou C and Upthegrove R
`(2018) Topiramate and Metformin Are
`Effective Add-On Treatments
`in Controlling Antipsychotic-induced
`Weight Gain: A Systematic Review
`and Network Meta-Analysis.
`Front. Pharmacol. 9:1393.
`doi: 10.3389/fphar.201 8.01393
`
`
`
`
`
`Frontiers in Pharmacology | www.frontiersin.org November 2018 | Volume9|Article 13931
`Exhibit 2098
`Slayback v. Sumitomo
`IPR2020-01053
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`Zhuoetal.
`Add-Onsfor Controlling Antipsychotic-Induced Weight Gain
`
`  
`Identification
`
`
`
`

      
`
` 
`
`Records identified through data-
`base searching
`(n = 614)
`
`through othersources
`(n = 0)
`
`(n = 599)
`
`
`
`
`
`Records after duplicates removed Additional records identified
`(n = 119)
` !"#$% & '  
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`(  " )  *'''   
`+
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`
`Screening
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`Eligibility
`
`
`
`Records screened
`(n = 599)
`
`Records excluded
`(n = 480)
`
`
`
`
`
`Full-text articles as-
`Full-text articles exclud-
`
`sessed foreligibility
`
`
`
`
`
`ed
`(n = 92)
`
`Studies included in full-review
`(n = 27)
`No. of studies on Metformin: 13
`
`No. of studies on Ranitidine: 2
`No. of studies on Topiramate: 4
`No. of studies on Sibutramine: 4
`
`No. of studies on Reboxetine: 3
`
`33S=
`
`FIGURE1 | PRISMA flowchart of study selection.
`
`
`
`Frontiers in Pharmacology | www.frontiersin.org November 2018 | Volume9| Article 13934
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