Can a Psychiatric Mental Health Nurse Practitioner (PMHNP) prescribe a Continuous Glucose Monitor (CGM) and metformin to a patient on Clozaril (clozapine) with antipsychotic-induced hyperglycemia?

PMHNP Prescribing Authority for CGM and Metformin in Clozapine-Induced Hyperglycemia

Yes, a PMHNP can and should prescribe both a continuous glucose monitor (CGM) and metformin for a patient on clozapine showing signs of antipsychotic-induced hyperglycemia, as metformin is specifically recommended to attenuate weight gain and metabolic complications in patients receiving antipsychotics with poor cardiometabolic profiles like clozapine. 1

Rationale for Metformin in Clozapine-Treated Patients

Metformin is the first-line pharmacological intervention for managing antipsychotic-induced metabolic complications. 1 The American Psychiatric Association recommends offering metformin concomitantly with antipsychotics that have poor cardiometabolic profiles to attenuate potential weight gain and metabolic disturbances. 1

Specific Evidence for Clozapine

• Clozapine is consistently associated with significant weight gain and metabolic abnormalities, including hyperglycemia, independent of adiposity. 2
• Clozapine has the largest number of reports linking it to new-onset type 2 diabetes and diabetic ketoacidosis among antipsychotics. 2, 3
• Clozapine directly induces hyperglycemia by inhibiting glucose transport and uptake, not solely through weight gain mechanisms. 4
• Among patients receiving atypical antipsychotics, significantly more patients on clozapine were found to have occult hyperglycemia (p = .001). 5

Metformin Dosing Protocol

Start metformin at 500 mg once daily, gradually increasing to 1000 mg twice daily as tolerated. 1 This titration minimizes gastrointestinal side effects while achieving therapeutic benefit.

• Modified-release metformin preparations should be used when available to minimize gastrointestinal side effects. 1
• Even low-dose metformin (500-1000 mg/d) has demonstrated efficacy in clozapine-treated patients, producing significant decreases in body weight and BMI over 12 weeks. 6
• Metformin achieves approximately 3% weight loss, with 25-50% of participants achieving at least 5% weight loss, and doses greater than 1500 mg are associated with the greatest weight loss. 1

Pre-Treatment Assessment

Before starting metformin, assess renal function, as it should be avoided in patients with renal failure. 1 Additionally, metformin should be considered in patients with diabetes and heart failure if eGFR >30 mL/min/1.73 m². 7

CGM Prescription Rationale

CGM is appropriate for monitoring antipsychotic-induced hyperglycemia, though it requires hospital protocols for guidance when used in inpatient settings. 7 For outpatient management by a PMHNP:

• CGM provides frequent measurements of interstitial glucose levels and trend data that can detect hypoglycemia and hyperglycemic patterns. 7
• In patients who use CGM in the ambulatory setting for self-management of diabetes, continued use is appropriate but requires access to specialist care. 7
• Real-time CGM data can be transmitted to healthcare providers for remote glucose management, which is particularly useful for psychiatric patients. 7

Monitoring Protocol

Establish baseline measurements before initiating treatment, including BMI, waist circumference, blood pressure, HbA1c, fasting glucose, lipid panel, liver function tests, complete blood count, and ECG. 1, 8

Ongoing monitoring schedule:

• Weight/BMI: monthly for the first 3 months, then quarterly. 8
• Blood pressure: recheck at 3 months, then annually. 8
• Fasting glucose and lipid panel: reassess at 3 months, then annually. 8
• Annual monitoring should include liver function, HbA1c, renal function, and vitamin B12. 1

Clinical Considerations

Patients with schizophrenia on clozapine require aggressive metabolic monitoring because they suffer increased mortality from cardiovascular disease, with contributions from modifiable risk factors including hyperglycemia. 2

• Hyperglycemia is common (30.1% prevalence) in patients treated with atypical antipsychotics who are thought to be euglycemic, making screening essential. 5
• Clozapine treatment may be associated with adverse effects on glucose metabolism independent of adiposity, requiring direct intervention beyond lifestyle modifications alone. 2
• Diabetes mellitus complications begin at glucose levels well below diabetic thresholds, justifying early intervention. 2

The PMHNP should not discontinue clozapine solely due to hyperglycemia, as clozapine is specifically recommended for treatment-resistant schizophrenia and suicide risk reduction. 7 Instead, aggressive metabolic management with metformin and CGM monitoring allows continuation of this essential psychiatric medication while mitigating metabolic risks.