University Medical Center Utrecht | MELIA

Antipsychotics are the mainstay treatment modality for schizophrenia. Of the insidious adverse drug reactions (ADRs) to antipsychotics, Antipsychotic-induced Weight Gain (AiWG) is the most debilitating and prevalent ADR. AiWG negatively impacts life expectancy, quality of life, treatment adherence, chances of developing type-2 diabetes and likelihood of remission. Treatment of AiWG is currently very challenging and few interventions have been investigated in well-powered trials of sufficient quality.

In the MELIA (the MEtformin-LIfestyle in Antipsychotic users trial) study, we aim to optimise the application of an existing drug, metformin, for a new indication, AiWG, by showing that metformin combined with lifestyle sessions reduces AiWG compared to placebo combined with lifestyle sessions. Furthermore, we aim to investigate the difference in reduction of AiWG between two  subgroups; clozapine use versus other antipsychotic use. At last, we aim to assess whether metformin compared to placebo improves metabolic traits, quality of life, general physical and psychological health, cost effectiveness and whether genetic liability to BMI and metabolic syndrome may help estimate weight reduction following initiation of metformin treatment. In case of reduction of AiWG due to metformin use in combination with lifestyle sessions, guidelines can implement AiWG as new indication for metformin.


  • University Medical Centre Utrecht


  • GGZ Centraal
  • Maastricht University
  • Vrije Universiteit Medical Centre


ZonMw – Good Use of Medicines

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