SELECTIVE SEROTONIN RE UPTAKE INHIBITORS AND GLYCEMIC OUTCOMES: A COMPARATIVE CLINICAL ANALYSIS OF SERTRALINE AND FLUOXETINE IN DIABETIC DEPRESSION

Abstract

Background: Depression is a common comorbidity in individuals with type 2 diabetes mellitus (T2DM), collectively referred to as “diabetic depression.” This dual disease burden significantly worsens glycemic control, increases cardiovascular risk, and impairs quality of life. Among antidepressants, selective serotonin reuptake inhibitors (SSRIs) are frequently used first-line agents, yet their metabolic profiles vary. This study provides a comparative evaluation of two widely prescribed SSRIs—sertraline and fluoxetine—with a focus on their glycemic, lipid, anthropometric, and psychiatric effects in diabetic patients.

Objective: To synthesize current clinical and pre-clinical evidence on the metabolic and psychiatric outcomes of sertraline and fluoxetine in patients with comorbid T2DM and depression, and to guide individualized antidepressant selection based on metabolic risk profiles.

Methods: A structured literature review was conducted, incorporating randomized controlled trials, meta-analyses, clinical guidelines, and pre-clinical studies. Comparative endpoints included changes in HbA1c, fasting blood glucose, lipid profiles, body weight, BMI, and depressive symptomatology (BDI-II scores). Mechanistic insights and adverse event profiles were also explored.

Results:
Both sertraline and fluoxetine demonstrated significant improvements in depressive symptoms and glycemic indices. Sertraline was associated with modest weight and waist circumference reductions, significantly lowered serum triglycerides, and stimulated counter-regulatory hormonal responses, including catecholamines and glucagon—posing a potential risk for hypoglycemia. In contrast, fluoxetine led to greater weight loss (~4.27 kg), improved insulin sensitivity through PI3K-AKT pathway modulation, and exhibited a lower propensity for inducing hypoglycemia.

Conclusions: Both SSRIs are effective for diabetic depression; however, their metabolic profiles differ. Sertraline may benefit patients with dyslipidemia but requires close monitoring for hypoglycemia. Fluoxetine may be preferable for patients with obesity or those requiring aggressive weight management. Individualized treatment based on comorbidities, metabolic goals, and tolerability is essential for optimizing outcomes in diabetic depression.