Impact of SGLT2 inhibitors on metabolic status in patients with psychiatric disorders undergoing treatment with second‑generation antipsychotics (Review)

Abstract

Metabolic dysfunctions have been reported in patients diagnosed with severe mental illnesses who are undergoing treatment with antipsychotics, especially second-generation agents. Sodium-glucose co-transporter 2 inhibitors (SGLT2Is) and glucagon-like peptide receptor agonists are new-generation antidiabetics whose favourable effects in the treatment of diabetes mellitus in the non-psychiatric population may raise interest in their use in patients presenting with severe mental illnesses and metabolic comorbidities possibly related to the use of antipsychotics. The objectives of this review were to investigate the evidence to support the use of SGLT2Is in this population and to find the most important aspects that need to be addressed by future research. A total of one preclinical trial, two guideline-format clinical recommendations, one systematic review and one case report were found, and their conclusions were analysed. The results support the following conclusions: i) SGLT2Is may be combined with metformin in selected cases of type 2 diabetes mellitus in the context of antipsychotic treatment, as they have been associated with favourable metabolic effects; and ii) data for the recommendation of SGLT2Is as second-line treatment in patients with diabetes mellitus who are also treated with olanzapine or clozapine are supported by very limited preclinical and clinical evidence. Further high-quality, large-scale research is needed in the field of the management of metabolic dysfunctions in patients with severe psychiatric illnesses who undergo treatment with second-generation antipsychotics.

Keywords: SGLT2 inhibitors; atypical antipsychotics; diabetes mellitus; metabolic syndrome; obesity; schizophrenia spectrum disorders.

Figure 1

Pathogenetic mechanisms of metabolic syndrome in patients undergoing treatment with second-generation antipsychotic agents (6-16). 5HT2C, 5-hydroxytryptamine receptor 2C; CCK, cholecystokinin; SNP, single nucleotide polymorphism.

Figure 2

Results of the screening and selection process. SGLT2I, sodium-glucose co-transporter 2 inhibitor.