Evidence map›Paper›PMID 42746377›Full record

ReviewCureus2026

Metabolic-Protective Strategies for Antipsychotic-Associated Weight Gain in Children and Adolescents: A Systematic Review.

Ali J Alhagawy, Ibrahim J Alhiqwi, Hamad A Majrabi, Ayoub H Salami, Mohammed S Aldawsari, Mohammed A Shok, Atyaf A Kariri, Ahlam M Muharraq, Raghad K Juraybi, Abdullah M Alghamdi and 1 more

Abstract readReview
In one paragraph

Review in Cureus, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Ali J AlhagawyDiabetic Center, Jazan Health Cluster, Jazan, SAU.
Ibrahim J AlhiqwiPsychiatry Department, Eradah Hospital, Jazan, SAU.
Hamad A MajrabiPsychiatry Department, Eradah Hospital, Jazan, SAU.
Ayoub H SalamiPsychiatry Department, Eradah Hospital, Jazan, SAU.
Mohammed S AldawsariPsychiatry Department, Eradah Hospital, Jazan, SAU.
Mohammed A ShokPsychiatry Department, Eradah Hospital, Jazan, SAU.
Atyaf A KaririPsychiatry Department, Eradah Hospital, Jazan, SAU.
Ahlam M MuharraqPsychiatry Department, Eradah Hospital, Jazan, SAU.
Raghad K JuraybiFaculty of Medicine, Jazan University, Jazan, SAU.
Abdullah M AlghamdiFaculty of Medicine, Tabuk University, Tabuk, SAU.
Abdulrahman M AlshaibanFaculty of Medicine, Tabuk University, Tabuk, SAU.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Second-generation antipsychotics are effective for a range of pediatric psychiatric and behavioral conditions but are commonly associated with weight gain and metabolic dysfunction. Metformin is the most extensively studied pharmacological strategy for preventing or treating this adverse effect; however, the randomized evidence base has evolved substantially with the publication of recent large trials. This study aimed to systematically review and meta-analyze randomized controlled trials of metformin and other metabolic-protective strategies, including topiramate, melatonin, and antipsychotic switching, for preventing or treating antipsychotic-associated weight gain in children and adolescents. PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for records published between January 2000 and June 2026. Randomized controlled trials enrolling participants aged 19 years or younger who were receiving a second-generation antipsychotic were eligible. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Random-effects meta-analyses using restricted maximum likelihood estimation with the Hartung-Knapp adjustment pooled mean differences and risk ratios when at least two trials contributed comparable data; prevention and treatment indications were analyzed separately. Seven unique randomized controlled trials reported across eight publications met eligibility criteria, including 1,871 participants: five trials evaluated metformin, one evaluated topiramate, and one evaluated melatonin. The pooled effect of metformin on body mass index (BMI) z-score, the primary outcome, favored treatment at all time windows but was not statistically significant (short-term, three trials: mean difference [MD] = -0.093, 95% confidence interval [CI] -0.250 to 0.063; medium-term, two trials: MD = -0.090, 95% CI -0.346 to 0.166; long-term, one trial: MD = -0.07, 95% CI -0.145 to 0.005). Short-term body weight was significantly reduced with metformin (three trials: MD = -2.30 kg, 95% CI -4.28 to -0.32). Metabolic laboratory outcomes were imprecise and inconsistent in direction, and diarrhea was numerically more frequent with metformin. Evidence for topiramate, melatonin, and antipsychotic switching was limited to single trials or trial arms. No included trial was rated as having an overall low risk of bias. Metformin has the largest randomized pediatric evidence base among metabolic-protective strategies and consistently attenuated weight gain compared with control; however, its pooled effect on the primary outcome did not reach statistical significance at any time window, and metabolic benefits could not be confirmed. Decisions regarding metabolic-protective strategies should be individualized rather than universally applied, and larger, longer, standardized pediatric trials are needed.

Indexed as

antipsychotic-associated weight gainbody mass index z-scorechildren and adolescentsmetabolic dysfunctionmetforminobesity preventionpediatric psychopharmacologyrandomized controlled trialssecond-generation antipsychoticssystematic review

Identifiers

PMID42746377
PMCPMC13577066

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.