Metformin for the prevention of antipsychotic-induced weight gain: guideline development and consensus validation
Open accessAbstract
BACKGROUND: Overweight and obesity are highly prevalent in people with severe mental illness (SMI). Antipsychotic-induced weight gain (AIWG) is one of the most commonly reported and distressing side effects of treatment and people living with SMI place a high value on the avoidance of this side effect. Metformin is the most effective pharmacological intervention studied for the prevention of AIWG yet clear guidelines are lacking and evidence has not translated into practice. The aim of this research was to develop a guideline for the use of metformin for the prevention of AIWG. STUDY DESIGN: The appraisal of guidelines for research and evaluation II instrument (AGREE II) was followed for guideline development. Literature was reviewed to address key health questions. The certainty of evidence was evaluated using GRADE methodology and an evidence-to-decision framework informed the strength of the recommendations. A consensus meeting was held where the algorithm and strength of recommendations were agreed. An independent external review was conducted involving experts in the field, including patient and public partners. STUDY RESULTS: Metformin is the only pharmacological agent that has demonstrated efficacy for preventing AIWG. Co-commencement with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg (95% CI -5.78 kg to -2.28 kg) compared to controls. A guideline for the use of metformin for the prevention of AIWG was developed with specific recommendations for co-commencement of metformin at initiation with an antipsychotic or commencement if certain criteria are present. Core recommendations were graded as strong by consensus agreement. CONCLUSIONS: This is the first published evidence-based guideline using the AGREE II framework and GRADE methods for the use of metformin to prevent AIWG incorporating recommendations for co-commencement. Implementation and evaluation of the guideline will be supported by a shared decision-making package and assessment of barriers and facilitators to implementation.
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Metformin is recommended across treatment guidelines for the prevention and management of antipsychotic-induced weight gain.
“At present, metformin, which is considered the first-line treatment for T2D globally, has shown evidence in the prevention and management of AIWG among patients, and is now recommended across treatment guidelines for this indication.14–17”
From The Effect of Semaglutide on Antipsychotic-Induced Weight Gain and Other Metabolic Parameters, among a Cohort of Inpatients (2026) · cites this paper as [14]
The Abstract (Study Results) and Results (Final Guideline Algorithm; page not available) recommend metformin for preventing antipsychotic-induced weight gain under specified conditions. The Results (Development of the Initial Guideline Contents; page not available) say some existing guidelines refer to early metformin use, but lack guidance on when and how to start it. This paper’s guideline is limited to prevention, so it does not establish a recommendation across treatment guidelines for both prevention and management. (LLM, conf=0.87)
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- [79]National Institute for Health and Care Excellence (NICE). Semaglutide for Managing Overweight and Obesity (TA875). 2023. 40080622
Cited by
Sorted by citations
De, R., Amin Alfatwa, Y., Kanagasundaram, P., Saragosa, J. E., Chan, J., Remington, G., Retnakaran, R., Sanches, M., Sockalingam, S., Agarwal, S. M., et al. (2026) · Schizophrenia Bulletin · doi:10.1093/schbul/sbaf236 · Cited by 1 · see citing works
“14 – 17 However, there are no clear, alternative phar macological options available for the significant subset of patients who do not respond to metfor min.”
Self-citation
- Authors
- Carolan, A., Hynes-Ryan, C., Agarwal, S. M., Bourke, R., Cullen, W., Gaughran, F., Hahn, M. K., Krivoy, A., Lally, J., Leucht, S., Lyne, J., McCutcheon, R. A., Norton, M. J., O’Connor, K., Perry, B. I., Pillinger, T., Shiers, D., Siskind, D., Thompson, A., O’Shea, D., Keating, D., & O’Donoghue, B.
- Affiliations
- Royal College of Surgeons in Ireland (IE)
- Centre for Addiction and Mental Health (CA)
- Saint John of God Hospital (IE)
- University College Dublin (IE)
- King's College London (GB)
- University of Copenhagen (DK)
- Tel Aviv University (IL)
- TUM Klinikum (DE)
- University College Cork (IE)
- University of Cambridge (GB)
- Greater Manchester Mental Health NHS Foundation Trust (GB)
- The University of Queensland (AU)
- The University of Melbourne (AU)
- School of Medicine, University College Dublin , Dublin, D04 V1W8 ,
- Corresponding author
- Carolan, Aoife
- ORCID
- Venue
- Schizophrenia Bulletin
- Publisher
- Oxford University Press (OUP)
- Published
- 2024-12-09
- Volume
- 51
- Issue
- 5
- Pages
- 1193-1205
- ISSN
- 0586-7614 (ISSN-L)
- 1745-1701
- PMC
- PMC12414565
- OpenAlex
- W4405222185
- Cited by
- 70
- References
- 79
- Citations by year
- 2026: 43 · 2025: 27
- FWCI
- 20.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Schizophrenia Bulletin (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc)
- Research Portal (King's College London) (submittedVersion, cc-by-nc)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc)
- Funders
- Health Research Board (APRO-2023-005)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Clinical practice guidelines implementation
- Keywords
- metformin, antipsychotic-induced weight gain
- MeSH terms
- Humans, Hypoglycemic Agents, Metformin, Antipsychotic Agents, Weight Gain, Practice Guidelines as Topic, Consensus, Overweight
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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