Metformin for obesity and glucose dysregulation in patients with schizophrenia receiving antipsychotic drugs

Abstract

Antipsychotic drug-induced weight gain and glucose dysregulation add to the cardiovascular risk of patients with schizophrenia and contribute to their early mortality. The currently recommended interventions to address the metabolic complications of antipsychotic drug treatment are to switch the patient from an antipsychotic drug with high metabolic liability to one with a lower liability and to implement lifestyle changes. These interventions can be quite challenging to carry out. So far the progress in improving the metabolic and cardiovascular outcome of patients with major mental illness has been disappointing. We offer an overview of the literature on metformin for antipsychotic drug-induced weight gain and glucose dysregulation and pertinent literature from the Diabetes Prevention Program. We conclude that young adults with schizophrenia newly exposed to antipsychotic drugs, who show a pattern of rapid weight gain and/or glucose dysregulation, are prime candidates for metformin if switching the antipsychotic medication to one with a lower metabolic burden is not an option or does not curtail the weight gain and/or adverse metabolic effects. Metformin therapy should not preclude healthy lifestyle interventions.

Update on Typical and Atypical Antipsychotic Drugs

“…It is possible that the results of this study will generalize to other atypical APDs, thereby permitting a reduction in the doses and a corresponding decrease in metabolic side effects (96). Metformin has been helpful to reverse weight gain in some recent studies (97). A recent meta-analysis of 23 studies, mean duration 62 weeks, found that atypical APDs as a group prevented relapse (29.0 versus 37%; p = 0.001), treatment failure (p = 0.003), and hospitalization (p = 0.004) (98).…”

Metformina: más allá del control glucémico

“…Asimismo, los efectos en la reducción del peso han sido inferiores a los producidos por los cambios en el estilo de vida o medicamentos aprobados para la reducción de peso 48,49 ; aunque algunos subgrupos presentan una mayor reducción de peso con el uso de metformina, tales como mujeres obesas en edad fértil con SOP 51 , niños y adolescentes con sobrepeso u obesidad, con mejor beneficio en el subgrupo de pacientes con resistencia a la insulina calculado por el índice Homeostasis Model Assessment, índice indirecto de insulinorresistencia 52 . Además, como protector en la ganancia de peso o como tratamiento de la misma, secundario a terapia con anti-psicóticos atípicos de segunda generación bien conocidos por sus efectos adversos cardiovasculares 53,54 .…”

Medication‐induced diabetes mellitus

“…A few studies also demonstrate improvement in metabolic parameters such as fasting glucose, but have not directly examined treatment of established diabetes associated with atypical antipsychotics. Some of the studies include lifestyle modification alone and in combination with metformin and they demonstrate additive effects of lifestyle and of metformin on weight management . However, maintaining lifestyle modification is particularly challenging in patients on antipsychotic medications.…”