The effects of fluoxetine on body weight, waist circumference, and body mass index in individuals who are overweight or have obesity: a meta-analysis of randomized controlled trials

Abstract

The effect of fluoxetine administration on body weight (BW), waist circumference (WC), and body mass index (BMI) remains inconclusive, as many studies have reported contradicting results. We conducted a meta-analysis of randomized controlled trials (RCTs) to assess the impact of fluoxetine prescription on these anthropometric indices. A comprehensive systematic review was conducted in PubMed/MEDLINE, SCOPUS, Web of Science, and EMBASE for manuscripts indexed before Jun 28st, 2025. The results were computed using the DerSimonian and Laird random effects model and reported as weighted mean differences (WMD) with 95% confidence intervals (CI). The current meta-analysis included 22 RCT arms (2348 individuals: placebo = 1166; fluoxetine = 1182) on BW, 2 RCT arms (77 individuals: placebo = 39; fluoxetine = 38) on WC, and 4 RCT arms (215 individuals: placebo = 105; fluoxetine = 110) on BMI. The present meta-analysis included 22 RCT arms (2348 individuals: placebo = 1166; fluoxetine = 1182) on BW. Fluoxetine treatment significantly reduced BW (WMD: -2.095 kg, p < 0.001), with significant heterogeneity noted among the RCTs (I² = 84.7%, P < 0.001). Fluoxetine supplementation decreased BW more substantially when the dose was ≥60 mg/day (WMD: -2.759 kg, p < 0.001) compared to <60 mg/day (WMD: -1.017 kg, p = 0.001), in trials lasting ≤12 weeks (WMD: -3.000 kg, p < 0.001) versus >12 weeks (WMD: -1.114 kg, p = 0.047), and when administered to individuals living with obesity (WMD: -2.246 kg, p < 0.001) compared to those living with overweight (WMD: -1.972 kg, p < 0.001). Fluoxetine did not impact WC or BMI values. Fluoxetine administration is associated with a reduction in BW, particularly when prescribed at doses ≥60 mg/day, during short-term interventions (≤3 months), and in individuals living with obesity.