Predicting Conversion to Insulin Sensitivity With Metformin: A Promising Tool for Clinicians in Addressing Insulin Resistance and Improving Outcomes in Patients With Treatment Resistant Bipolar Depression

Abstract

Background: Insulin resistance (IR) changes the trajectory of responsive bipolar disorder to a treatment-resistant course. A clinical trial conducted by our group demonstrated that IR reversal by metformin improved clinical and functional outcomes in treatment-resistant bipolar depression (TRBD). To aid clinicians identify which metformin-treated TRBD patients might reverse IR, and given strong external evidence for their association with IR, we developed a predictive tool using body mass index (BMI) and homeostatic model assessment-insulin resistance (HOMA-IR).

Methods: The predictive performance of baseline BMI and HOMA-IR was tested with a logistic regression model using known metrics: area under the receiver operating curve, sensitivity, and specificity. In view of the high benefit to low risk of metformin in reversing IR, high sensitivity was favored over specificity.

Results: In this BMI and HOMA-IR model for IR reversal, the area under the receiver operating curve is 0.79. At a cutoff probability of conversion of 0.17, the model's sensitivity is 91% (95% confidence interval [CI], 57%-99%), and the specificity is 56% (95% CI, 36%-73%). For each unit increase in BMI or HOMA-IR, there is a 15% (OR, 0.85; 95% CI, 0.71-0.99) or 43% (OR, 0.57; CI, 0.18-1.36) decrease in the odds of conversion, respectively.

Conclusions: In individuals with TRBD, this tool using BMI and HOMA-IR predicts IR reversal with metformin with high sensitivity. Furthermore, these data suggest early intervention with metformin at lower BMI, and HOMA-IR would likely reverse IR in TRBD.