Fluoxetine and metformin combined treatment decreases insulin resistance in patients with metabolic syndrome

Objective: To determine if brain serotonergic activity increase induced by the treatment with fluoxetine plus metformin can decrease insulin resistance (IR) in adolescents with metabolic syndrome (MetS). Methods: A quasi-experimental study was conducted in 40 adolescents with MetS and IR. IR was determined through homeostatic model assessment (HOMA). After IR was determined in MetS patients, treatment with fluoxetine and metformin was started and continued for 20 weeks. At the beginning and at the end of treatment, all patients had L-tryptophan free fraction (FFT), glucose and insulin plasma levels determined, as well as HOMA, lipid profile and intensity-dependent auditory-evoked potentials (IDAEPs) in order to measure brain 5-HT activity. Results: At baseline, the adolescents had obesity, hyperglycemia, hyperinsulinemia, IR, dyslipidemia and decreased FFT, as well as a steeper AFS slope of the N1/ P2 component of IDAEPs. The treatment with Fluoxetine and metformin reduced body weight, glucose, insulin, triglycerides and LDL-cholesterol and caused an increase in plasma FFT and decrease in the slope of the N1/P2 component of IDAEPs. Interestingly, the treatment also decreased IR at 20 weeks. Conclusion: This work shows that the combined treatment with fluoxetine and metformin decreases insulin resistance concurrently with an increase in brain serotonergic metabolic and functional activity, expressed by an increase in plasma FFT and a decrease in the N1/P2 ASF slope of the IDAEPs in patients with MetS.