open access publication

Article, 2024

Metformin co-commencement at time of antipsychotic initiation for attenuation of weight gain: a systematic review and meta-analysis

Therapeutic Advances in Psychopharmacology, ISSN 2045-1253, 2045-1261, Volume 14, Page 20451253241255476, 10.1177/20451253241255476

Contributors

Yu, Ou (Corresponding author) [1] Lu, Mengyao [1] [2] Lai, Terence K Y [1] Hahn, Margaret Karolina 0000-0001-8884-9946 [3] [4] Agarwal, Sri Mahavir 0000-0002-2705-5146 [3] [4] O'Donoghue, Brian N 0000-0001-6240-6952 [5] [6] Ebdrup, Bjørn Hylsebeck 0000-0002-2590-5055 [7] Siskind, Dan J 0000-0002-2072-9216 [1] [2]

Affiliations

  1. [1] University of Queensland
    2. [NORA names: Australia; Oceania; OECD];
  2. [2] Metro South Health
    3. [NORA names: Australia; Oceania; OECD];
  3. [3] Centre for Addiction and Mental Health
    4. [NORA names: Canada; America, North; OECD];
  4. [4] University of Toronto
    5. [NORA names: Canada; America, North; OECD];
  5. [5] St. Vincent's University Hospital
    6. [NORA names: Ireland; Europe, EU; OECD];

Abstract

Background: Antipsychotic medications are associated with weight gain and metabolic derangement. However, comprehensive evidence for the efficacy of co-commenced pharmacological treatments to mitigate initial weight gain is limited. Metformin has been shown to be effective in reducing weight among people on antipsychotic medications who are already overweight, but the potential benefits of metformin co-commencement in mitigating antipsychotic-induced weight gain has not been systematically reviewed. Method: We conducted a systematic review of PubMed, EMBASE, PsychInfo, CINAHL, the Cochrane database, and China National Knowledge Infrastructure from inception to 18 November 2023. We undertook a meta-analysis of concomitant commencement of metformin versus placebo for attenuation of weight gain and metabolic syndrome for people with schizophrenia commencing a new antipsychotic. Results: Fourteen studies from Australia, United States, Venezuela, and China with 1126 participants were included. We found that metformin was superior to placebo in terms of attenuating weight gain (-3.12 kg, 95% CI -4.22 to -2.01 kg). Metformin also significantly attenuated derangement of fasting glucose levels, total cholesterol, and total triglyceride levels. Sensitivity analysis on study quality, duration, and antipsychotic agent did not impact the results. Meta-analysis was also conducted on adverse drug reactions (ADR) reported in each study which showed no significant difference in ADR incidence between metformin and placebo groups. Subgroup analysis on antipsychotic-naïve participants and participants switching to new antipsychotic did not impact the results. Conclusion: Metformin led to statistically significant and clinically meaningful attenuation of weight gain as well as attenuation of several other metabolic parameters when commenced concomitantly with antipsychotic medications. Co-commencement of metformin with antipsychotic medications, where tolerated, should be considered in the clinical setting with aim to improve long-term cardiometabolic outcomes for patients with long-term need of antipsychotic treatments.

Keywords

Australia, CINAHL, China, China National Knowledge Infrastructure, Cochrane, Cochrane Database, Embase, Knowledge Infrastructure, National Knowledge Infrastructure, PsychINFO, PubMed, United States, Venezuela, adverse drug reaction incidence, adverse drug reactions, agents, analysis, antipsychotic agents, antipsychotic initiation, antipsychotic medication, antipsychotic treatment, antipsychotic-induced weight gain, antipsychotics, associated with weight gain, attenuated derangements, attenuated weight gain, attenuation, attenuation of weight gain, cardiometabolic outcomes, cholesterol, clinic, clinical setting, clinically meaningful attenuation, comprehensive evidence, database, derangements, differences, drug reactions, duration, efficacy, evidence, fasting glucose levels, gain, glucose levels, group, inception, incidence, infrastructure, initial weight gain, initiation, levels, long-term cardiometabolic outcomes, long-term needs, medication, meta-analysis, metabolic derangements, metabolic parameters, metabolic syndrome, metformin, needs, no significant difference, outcomes, parameters, participants, patients, people, pharmacological treatment, placebo, placebo group, potential benefits, quality, reaction, reduce weight, results, review, review of PubMed, schizophrenia, sensitivity, sensitivity analysis, sets, significant difference, state, study, study quality, subgroup analysis, subgroups, syndrome, systematic review, systematic review of PubMed, time, total cholesterol, total triglyceride levels, treatment, triglyceride levels, units, weight, weight gain

Funders

  • National Health and Medical Research Council
  • Centre for Addiction and Mental Health
  • Novo Nordisk Foundation
  • Canadian Institutes of Health Research
  • Physicians' Services Incorporated Foundation

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