Clozapine is a most effective agent for treatment-resistant schizophrenia, but is associated with obesity, hypertension, dyslipidaemia and type 2 diabetes mellitus (T2DM). Clozapine causes weight gain and insulin resistance independent of adiposity. There is an excess of cardiovascular deaths in those on long-term clozapine.

We reviewed the prevalence and management of diabetes, and associated comorbidities among 175 Alfred Health outpatients receiving clozapine. A cross-sectional review of demographic characteristics and glucose parameters was performed. The twelve patients who had attended the diabetes outpatient clinic on at least one occasion were analysed further.

The mean age of the 175 patients studied was 47 ± 13.4 years (SD); 67% (n=118) were men. Almost 20% (n=34) had a confirmed diagnosis of T2DM. An additional 6% (n=11) had single fasting glucose levels >6.9 mmol/L and 17% (n=29) had impaired fasting glycaemia. 42% (n=74) of the entire cohort had evidence of abnormal glucose metabolism. 86% (n=151) of patients had either a fasting glucose level or HbA1c measured within the last 24 months.

The mean age of the twelve patients with T2DM attending our clinic was 50.9 ± 14 years; 75% (n=9) were men. All were overweight or obese with a mean BMI of 31.7 ± 3.9 kg/m2. The mean duration of schizophrenia and clozapine treatment was 28.8 ± 15.4 years and 8.6 ± 4.8 years respectively. The mean duration of T2DM was 7.3 ± 3.1 years with an average of 4.8 ± 5.1 visits to the clinic. The mean HbA1c value at the first clinic visit was 7.5 ± 2.1% and 7.1 ± 2.3% at the last. Patients were managed on oral hypoglycaemic agents (OHA) alone (n=5), or OHA plus GLP-1 agonist (n=2), OHA plus GLP-1 agonist plus insulin (n=2), diet (n=2), and OHA plus insulin (n=1). Very few patients had evidence of diabetes complications. Additional cardiovascular risk factors were prominent (75% currently smoking, 58% hypertension, 83% dyslipidaemia).

Clozapine-treated patients have higher rates of T2DM and cardiovascular risk factors such as obesity, hypertension, dyslipidaemia and smoking than the general population contributing to excess morbidity and mortality. Management of T2DM in this group remains a challenge.