The impact of fluoxetine on obesity and diabetes-related biomarkers in overweight and obese individuals: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), is widely used in clinical practice for managing depression and anxiety. Emerging evidence suggests fluoxetine may influence body weight (BW) and glucose metabolism, yet its potential benefits in overweight or obese individuals remain unclear. This systematic review and meta-analysis aimed to evaluate the impact of fluoxetine on obesity-related parameters and diabetes-related biomarkers in overweight and obese adults.

METHODS

We systematically searched four major databases (Scopus, Web of Science, Embase, and PubMed/MEDLINE) following PRISMA guidelines for randomized controlled trials (RCTs) evaluating the effects of fluoxetine on BW, fasting blood sugar (FBS), and glycated hemoglobin (HbA1c) in overweight or obese individuals. Data were pooled using a random-effects model, and subgroup analyses were conducted based on fluoxetine dose, intervention duration, and obesity classification.

RESULTS

Results

A total of 26 RCTs met the inclusion criteria. Fluoxetine administration was associated with a significant reduction in BW (WMD: − 2.095 kg; 95% CI: − 2.806 to − 1.385; p < 0.001), particularly at doses ≥ 60 mg/day and in studies lasting ≤ 12 weeks. FBS (WMD: − 8.70 mg/dL; 95% CI: − 17.25 to − 0.14; p = 0.046) and HbA1c (WMD: − 0.61%; 95% CI: − 1.22 to − 0.016; p = 0.044) also decreased significantly. Notably, while BW reduction was greater in shorter trials (≤ 12 weeks), HbA1c improvement was more pronounced in longer trials (> 12 weeks), especially among obese individuals (BMI ≥ 30 kg/m²).

CONCLUSIONS

Fluoxetine was associated with modest but statistically significant reductions in BW, FBS, and HbA1c levels in overweight and obese individuals. The greatest weight loss was observed at doses ≥ 60 mg/day over shorter durations (≤ 12 weeks), whereas greater reductions in HbA1c were seen in longer trials (> 12 weeks) at similar dosages.