Liraglutide Used to Mitigate Diabetes Risk in Patients With Schizophrenia

Patients with schizophrenia are at high risk of developing diabetes, particularly due to the effects of antipsychotic medications. However, the results of a recently published trial indicate liraglutide can help improve glucose tolerance and body weight in prediabetic patients.

Presenting a difficult conundrum for prescribers and patients, the antipsychotic medications used to treat the symptoms of schizophrenia can cause metabolic imbalances and increased appetite, potentially leading to weight gain and type 2 diabetes (T2D). A group of researchers hypothesized that the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide, which is already used to treat T2D and obesity, could be effective in counteracting the effects of antipsychotics in this population.

In the study, published in JAMA Psychiatry, researchers randomized 103 adults with schizophrenia to receive either liraglutide or a placebo for 16 weeks. All participants were obese and had prediabetes, as determined by body mass index and levels of glucose and glycated hemoglobin. They continued their normal antipsychotic regimens of clozapine or olanzapine throughout the study.

Researchers evaluated the primary endpoint, change in glucose tolerance over the 16-week period, and found that it had improved significantly for the group taking liraglutide, as they had achieved a 23% larger reduction in glucose during the test compared with the placebo arm.

Patients were significantly more likely to improve from being prediabetic to having normal glucose tolerance if they had received liraglutide (63.8% vs 16.0% in the placebo group). The liraglutide group also showed greater improvements in glycated hemoglobin level, plasma glucose level, and other measures of glucose control.

Furthermore, the liraglutide group demonstrated significantly larger reductions in weight, waist circumference, systolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol. Body scans showed that this group’s visceral fat and total body fat had decreased, but these improvements were not significant after sensitivity analyses.

Serious adverse events were rare, and more prevalent in the placebo group than the liraglutide group. However, there was a small yet significant increase in amylase levels among the liraglutide group, and they also were more likely to report nausea, although this became less frequent over the study period. There were no differences in quality of life, functioning, psychiatric disease severity, or alcohol intake between the 2 study groups.

Based on these findings, the researchers suggested that liraglutide could be an effective and feasible therapy to help manage the weight gain and glucose control problems that can accompany antipsychotics, particularly in a population already at high risk of developing T2D. They called for further research on the safety and efficacy of liraglutide and other GLP-1 receptor agonists in these patients.

In summary, the study authors described liraglutide as “a safe and effective pharmacologic intervention” in combination with clozapine and olanzapine. “Liraglutide improved glucose tolerance and metabolic variables and induced a body weight loss superior to that of placebo without adversely affecting the mental status of the participants,” they concluded.