Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jul 12:14:1215807.
doi: 10.3389/fpsyt.2023.1215807. eCollection 2023.

The potential effect of metformin on cognitive and other symptom dimensions in patients with schizophrenia and antipsychotic-induced weight gain: a systematic review, meta-analysis, and meta-regression

Vera Battini  1 , Giovanna Cirnigliaro  2 , Rodolfo Leuzzi  2 , Eleonora Rissotto  2 , Giulia Mosini  1 , Beatrice Benatti  2   3 , Marco Pozzi  4 , Maria Nobile  4 , Sonia Radice  1 , Carla Carnovale  1 , Bernardo Dell'Osso  2   3   5   6 , Emilio Clementi  1   4
Affiliations
Review

The potential effect of metformin on cognitive and other symptom dimensions in patients with schizophrenia and antipsychotic-induced weight gain: a systematic review, meta-analysis, and meta-regression

Vera Battini et al. Front Psychiatry. .

Abstract

Introduction: Metformin has shown good efficacy in the management of antipsychotic-induced metabolic syndrome (MetS) in patients with schizophrenia or schizoaffective disorders. Its ability to induce antidepressant behavioural effects and improve cognitive functions has also been investigated: yet information has not been systematized. The aim of this study was therefore to investigate the effects of metformin on cognitive and other symptom dimension in schizophrenic patients treated with antipsychotics through a systematic review and meta-analysis.

Methods: We searched PubMed, ClinicalTrials.Gov, Embase, PsycINFO, and WHO ICTRP database up to February 2022, Randomised Controlled Trials (RCT) evaluating patients diagnosed with schizophrenia and related disorders, who were treated with metformin as add-on therapy to antipsychotics for the treatment of weight gain and in which changes in psychiatric symptoms and cognitive functions were evaluated.

Results: A total of 19 RCTs met the inclusion criteria. Meta-analysis was performed on 12 eligible studies. We found a positive trend after 24 weeks of treatment in schizophrenic patients with stable conditions [SMD (95%CI) = -0.40 (-0.82;0.01), OR (95%CI) = 0.5 (-2.4;3.4)]. Better performance was detected in the Brief Assessment of Cognition in Schizophrenia and Positive and Negative Syndrome Scale (PANSS) with low heterogeneity among studies. One study reported changes in BACS-verbal memory subdomain in favour of placebo [MD (95%CI) = -16.03 (-23.65;8.42)]. Gastrointestinal disorders, xerostomia, and extrapyramidal syndrome were the most reported adverse effects. Psychiatric adverse events were also described: in particular, symptoms attributable to a relapse of schizophrenia.

Conclusion: Some degree of efficacy was found for Metformin in improving cognitive and other symptom dimensions in patients with Schizophrenia. Given the clinical relevance of this potential pharmacological effect, longer specific studies using adequate psychometric scales are strongly recommended. Likewise, how metformin acts in this context needs to be evaluated in order to enhance its efficacy or find more efficacious drugs.

Keywords: cognitive disorders; hypoglycemic drugs; meta-analysis; metformin; schizophrenia.

PubMed Disclaimer

Conflict of interest statement

BD’O has received lecture honoraria that are not related to the work submitted for publication, from Angelini, Janssen, Lundbeck, Bromatech, Otzuka, and Neuraxpharm. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The PRISMA 2020 flowchart.
Figure 2
Figure 2
Metformin compared to Placebo considering all scales.
Figure 3
Figure 3
Sub-group analysis at twelve weeks.
Figure 4
Figure 4
Sub-group analysis at twenty-four weeks.
Figure 5
Figure 5
The influence of BMI at baseline, meta-regression.
Figure 6
Figure 6
Risk of Bias of the included studies.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Charlson FJ, Ferrari AJ, Santomauro DF, Diminic S, Stockings E, Scott JG, et al. . Global epidemiology and burden of schizophrenia: findings from the global burden of disease study 2016. Schizophr Bull. (2018) 44:1195–203. doi: 10.1093/SCHBUL/SBY058 - DOI - PMC - PubMed
    1. Kahn RS, Sommer IE, Murray RM, Meyer-Lindenberg A, Weinberger DR, Cannon TD, et al. . Schizophrenia. Nat Rev Dis Primers. (2015) 1:15067. doi: 10.1038/NRDP.2015.67 - DOI - PubMed
    1. De Hert M, Correll CU, Bobes J, Cetkovich-Bakmas M, Cohen DAN, Asai I, et al. . Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care. World Psychiatry. (2011) 10:52–77. doi: 10.1002/J.2051-5545.2011.TB00014.X - DOI - PMC - PubMed
    1. Leucht S, Cipriani A, Spineli L, Mavridis D, Örey D, Richter F, et al. . Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. (2013) 382:951–62. doi: 10.1016/S0140-6736(13)60733-3 - DOI - PubMed
    1. DeJongh BM. Clinical pearls for the monitoring and treatment of antipsychotic induced metabolic syndrome. Ment Health Clin. (2021) 11:311–9. doi: 10.9740/MHC.2021.11.311 - DOI - PMC - PubMed