How does Rexulti (brexpiprazole) affect blood sugar levels?

Rexulti (Brexpiprazole) and Blood Sugar Effects

Brexpiprazole (Rexulti) can cause hyperglycemia and may increase the risk of developing diabetes, requiring blood glucose monitoring in patients taking this medication. 1

Mechanism and Risk

Brexpiprazole belongs to the class of second-generation antipsychotics, which are known to affect glucose metabolism. According to the FDA drug label, brexpiprazole can cause:

• Hyperglycemia (high blood sugar)
• Diabetes mellitus
• In extreme cases, diabetic ketoacidosis, hyperosmolar coma, or death 1

The American Diabetes Association specifically mentions second-generation antipsychotic medications as drugs that should be considered when deciding whether to screen for prediabetes or diabetes, as these medications are known to increase the risk of these conditions 2.

Monitoring Recommendations

For patients taking brexpiprazole, the following monitoring protocol is recommended:

• Baseline screening: Assess fasting plasma glucose before or soon after starting brexpiprazole
• Ongoing monitoring: Monitor blood glucose periodically during long-term treatment 1
• High-risk patients: More frequent monitoring may be needed for patients with pre-existing diabetes or risk factors for diabetes

Clinical Evidence of Hyperglycemic Effects

In clinical trials of brexpiprazole for schizophrenia:

• 8% of adult patients with normal baseline fasting glucose experienced a shift to high levels while taking brexpiprazole
• 17% of patients with borderline fasting glucose experienced shifts to high levels
• Combined, 10% of patients with normal or borderline fasting glucose experienced shifts to high fasting glucose during long-term studies 1

In clinical trials for adjunctive treatment of major depressive disorder:

• 5% of adult patients with normal baseline fasting glucose experienced a shift to high while taking brexpiprazole plus an antidepressant
• 25% of patients with borderline fasting glucose experienced shifts to high
• Combined, 9% of patients with normal or borderline fasting glucose experienced shifts to high fasting glucose during long-term depression studies 1

Comparison to Other Antipsychotics

The metabolic effects of second-generation antipsychotics vary across medications:

• Aripiprazole and ziprasidone tend to have fewer metabolic effects
• Haloperidol, clozapine, quetiapine, and risperidone tend to have more metabolic effects 2

Brexpiprazole shows moderate metabolic effects compared to other antipsychotics. It demonstrates small changes in metabolic parameters that were not clinically significant in most patients, but with moderate weight gain that could indirectly affect glucose metabolism 3.

Clinical Approach for Patients on Brexpiprazole

1. For patients starting brexpiprazole:

   • Obtain baseline fasting glucose levels
   • Educate about symptoms of hyperglycemia (increased thirst, frequent urination, hunger, weakness, confusion, fruity breath)
   • Schedule follow-up glucose testing within 12-16 weeks 2

2. For patients already on brexpiprazole:

   • Monitor fasting glucose at least annually
   • Consider more frequent monitoring for those with risk factors for diabetes
   • Watch for weight gain, which may contribute to glucose abnormalities

3. For patients with diabetes taking brexpiprazole:

   • More frequent glucose monitoring is essential
   • Diabetes medication adjustments may be necessary
   • Consider consultation with endocrinology if glucose control worsens significantly

Risk Mitigation

To minimize the risk of adverse metabolic effects:

• Consider alternative medications in patients with pre-existing diabetes or multiple diabetes risk factors
• Monitor weight regularly, as weight gain can exacerbate glucose abnormalities
• Encourage lifestyle modifications (diet, exercise) to counteract potential metabolic effects
• Consider switching to an antipsychotic with lower metabolic risk if significant glucose abnormalities develop

Common Pitfalls to Avoid

1. Failure to obtain baseline glucose measurements before starting brexpiprazole
2. Inadequate follow-up monitoring, especially in the first few months of treatment
3. Overlooking symptoms of hyperglycemia in patients taking brexpiprazole
4. Not considering medication interactions that might further affect glucose metabolism
5. Attributing all glucose changes to brexpiprazole without considering other factors (diet, weight gain, other medications)

Remember that while brexpiprazole can affect glucose metabolism, the benefits of treatment may outweigh these risks for many patients. Close monitoring and appropriate interventions can help manage these effects effectively.