Atypical antipsychotic drugs have been associated with metabolic changes including hyperglycemia/diabetes mellitus, dyslipidemia, and body weight gain. While all drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile. 

Hyperglycemia/Diabetes Mellitus

Hyperglycemia, in some cases extreme and associated with diabetic ketoacidosis, hyperosmolar coma, or death, have been reported in patients treated with atypical antipsychotics. There have been reports of hyperglycemia in patients treated with aripiprazole [see Adverse Reactions (6.1)]. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse reactions is not completely understood. However, epidemiological studies suggest an increased risk of hyperglycemia-related adverse reactions in patients treated with the atypical antipsychotics. 

Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics, including ABILIFY ASIMTUFII, should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes), who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics, including ABILIFY ASIMTUFII, should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics, including ABILIFY ASIMTUFII, should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the atypical antipsychotic drug.

In a short-term, placebo-controlled randomized trial in adults with schizophrenia, the mean change in fasting glucose was +9.8 mg/dL (N=88) in the Abilify Maintena-treated patients (once monthly dosing) and +0.7 mg/dL (N=59) in the placebo-treated patients. Table 3 shows the proportion of Abilify Maintena-treated patients with normal and borderline fasting glucose at baseline and their changes in fasting glucose measurements. 

During a 52-week, open-label bipolar I disorder study in those patients who initiated Abilify Maintena treatment, 1.1% with normal baseline fasting glucose experienced a shift to high while receiving Abilify Maintena and 9.8% with borderline fasting glucose experienced a shift to high. Combined, 2.9% of these patients with normal or borderline fasting glucose experienced shifts to high fasting glucose during this trial.

Dyslipidemia

Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics.

Table 4 shows the proportion of adult patients from one short-term, placebo-controlled randomized trial in adults with schizophrenia taking Abilify Maintena (once monthly dosing), with changes in total cholesterol, fasting triglycerides, fasting LDL cholesterol and HDL cholesterol. 

During a 52-week, open-label bipolar I disorder study in those patients who initiated Abilify Maintena, shifts from baseline in fasting cholesterol from normal to high were reported in 2.1% (total cholesterol) and 2.2% (LDL cholesterol) and shifts from baseline from normal to low were reported in 8.5% (HDL cholesterol). Of these patients with normal baseline triglycerides, 3.6% experienced shifts to high, and 0.0% experienced shifts to very high. Combined, 1.0% of these patients with normal or borderline fasting triglycerides experienced shifts to very high fasting triglycerides during this trial.

Weight Gain

Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.

In one short-term, placebo-controlled trial in adult patients with schizophrenia with Abilify Maintena (once monthly dosing), the mean change in body weight at Week 12 was +3.5 kg (N=99) in the Abilify Maintena-treated patients and +0.8 kg (N=66) in the placebo-treated patients. 

Table 5 shows the percentage of adult patients with schizophrenia with weight gain ≥7% of body weight in a short-term, placebo-controlled trial with Abilify Maintena. 

During a 52-week, open-label bipolar I disorder study in those patients who initiated Abilify Maintena, 1.8% discontinued Abilify Maintena treatment due to weight increase. Abilify Maintena was associated with mean increase from baseline in weight of 1.0 kg at Week 52. In this trial, 21.4% of these patients demonstrated ≥7% increase in body weight and 15.4% demonstrated a ≥7% decrease in body weight.