Sustained Weight Loss After Treatment With a Glucagon-Like Peptide-1 Receptor Agonist in an Obese Patient With Schizophrenia and Type 2 Diabetes

To the Editor: Obesity, diabetes, and cardiovascular disease associated with antipsychotics represent major unresolved clinical issues that contribute to the increasing mortality gap between patients with schizophrenia and the general population (1). At best, current interventions against antipsychotic-induced weight gain (e.g., metformin) facilitate a weight loss of up to 3 kg, but the long-term stability of this weight reduction is questionable (2). Glucagon-like peptide-1 (GLP-1) receptor agonists efficiently reduce blood glucose levels and confer only a negligible risk of hypoglycemia. For these reasons, GLP receptor agonists are widely used in the treatment of type 2 diabetes. GLP-1 receptor agonists stimulate glucose-induced insulin secretion, inhibit glucagon secretion, and reduce gastrointestinal motility, which reduce appetite and food intake. Ultimately, this also leads to weight loss in patients without type 2 diabetes (3). Currently, Novo Nordisk is pursuing U.S. Food and Drug Administration approval for liraglutide for obesity.

This case report describes the effects of GLP-1 receptor agonist treatment in a schizophrenia patient with antipsychotic-induced obesity and type 2 diabetes. The patient provided consent for publication.

Case Report

A 60-year-old woman with clozapine-treated disorganized schizophrenia (hebephrenia) and a past history of drug abuse was referred to our diabetes outpatient clinic for dysregulated type 2 diabetes. The patient had been living in supported housing for 19 years.

Clinical and biochemical data from somatic and psychiatric records covering a 2-year period were obtained. At referral, the patient weighed 89 kg (body mass index, 33.5), and her glycated hemoglobin A_1c (HbA_1c) level was 10.0%. She was being treated with clozapine (375 mg/day), insulin (44 IU/day, biphasic insulin aspart), metformin (2 g/day), and simvastatin (10 mg/day). We initiated add-on treatment with liraglutide (0.6 mg/day, subcutaneous injection), which was well tolerated, and self-administration was uncomplicated. After 3 weeks, the liraglutide dosage was increased to 1.2 mg/day, and after 8 months it was increased to 1.8 mg/day.

Three months of treatment reduced her HbA_1c level to 8.9% and her body weight by 5.1 kg. After 2 years of treatment, her total weight loss was 7.7 kg (an 8.7% body weight reduction) (Figure 1). After 14 months, her HbA_1c level was less than 6.5%, and the amount of insulin needed gradually decreased (28 IU/day). The patient’s lifestyle and psychiatric status were stable during the 2-year period (a score of 30 on the Global Assessment of Functioning Scale), without hospital admissions.

Discussion

Two years of liraglutide treatment markedly decreased HbA_1c levels and resulted in a substantial weight loss in an obese patient with schizophrenia and dysregulated diabetes. To our knowledge, this is the first clinical evidence supporting the use of GLP-1 receptor agonists in the treatment of antipsychotic-induced weight gain (2).