Potential Role of the Triple Receptor Agonist Retatrutide in Antipsychotic-Associated Metabolic Dysfunction Among Clozapine- and Olanzapine-Treated Schizophrenia Spectrum Disorders: A Narrative Review and Theoretical Framework.

Narrative review

“This narrative review examines the rationale for investigating retatrutide in this setting, drawing on retatrutide trials in non-psychiatric populations, the pathophysiology of antipsychotic-induced weight gain, and emerging evidence for incretin-based therapies in antipsychotic-treated populations.”

Patients with schizophrenia spectrum disorders receiving clozapine or olanzapine

“This review focuses on patients with schizophrenia spectrum disorders receiving these two agents, in whom the relevant psychiatric evidence is concentrated.”

GLP-1 receptor agonists in clozapine- or olanzapine-treated patients report reductions in body weight and glycemic impairment without evidence of worsening psychotic symptoms.

“Indirect support comes from randomized trials and meta-analyses of GLP-1RAs in clozapine- or olanzapine-treated patients, which report reductions in body weight and glycemic impairment without evidence of worsening psychotic symptoms.”

The glucagon component of retatrutide increases basal energy expenditure, a pathway not engaged by mono- or dual agonists.

“The glucagon component is of particular mechanistic interest because it increases basal energy expenditure, a pathway not engaged by mono- or dual agonists”