Reducing Metabolic Adverse Effects of Antipsychotic Drugs: A New Approach

People with schizophrenia are vulnerable to metabolic disorders. Glucagon-like peptide-1 (GLP-1) receptor agonists, a new class of agents used to treat type 2 diabetes, increase insulin secretion and, at higher doses, reduce weight, without affecting insulin receptors. Investigators in Denmark conducted an industry-sponsored, 16-week, randomized, placebo-controlled trial of subcutaneous liraglutide, a GLP-1 agonist, in 103 patients with schizophrenia spectrum disorders treated with clozapine or olanzapine, the two antipsychotic drugs with the highest incidence of weight gain and metabolic disturbances.

All participants had elevated body-mass index values and prediabetes (e.g., elevated fasting blood sugar or glycosylated hemoglobin [HgbA_1c] levels) but not diabetes; 96 patients completed the trial. Oral glucose tolerance tests normalized in almost four times as many liraglutide patients as placebo patients (number needed to treat, 2). Compared with placebo, liraglutide was associated with 5.3 kg more weight loss and 4.1 cm greater decrease in waist circumference, with large effect sizes. Liraglutide was also associated with greater decreases in HgbA_1c and significant improvements in lipid profiles.