The impact of sertraline treatment on obesity, inflammation, blood pressure, and lipid profiles: a systematic review and meta-analysis of randomized controlled trials

Objective: Sertraline, a commonly prescribed selective serotonin reuptake inhibitor (SSRI), is widely used for the treatment of depression. While its psychotropic benefits are well established, its effects on metabolic and cardiovascular health remain uncertain. This systematic review and meta-analysis aimed to evaluate the impact of sertraline on obesity, inflammation, glycemic control, blood pressure, and lipid profiles in adults. Methods: A comprehensive literature search was conducted across five databases through August 2025. A total of 16 studies comprising 17 intervention arms were included. Data were synthesized using a random-effects model, and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated for each outcome. Results: Sertraline use was associated with significant reductions in body mass index (WMD: − 1.59 kg/m²; 95% CI: − 2.72 to − 0.47; p = 0.005), body weight (BW) (WMD: − 2.21 kg; 95% CI: − 4.40 to − 0.02; p = 0.048), systolic blood pressure (SBP) (WMD: − 3.82 mmHg; 95% CI: − 7.48 to − 0.16; p = 0.041), C-reactive protein(CRP) (WMD: − 0.21 mg/dL; 95% CI: − 0.26 to − 0.16; p < 0.001), interleukin-6 (IL-6) (WMD: − 5.91 pg/ml; 95% CI: − 11.33 to − 0.49; p = 0.032), and glycated hemoglobin (HbA1c) (WMD: − 0.51%; 95% CI: − 0.91 to − 0.11; p = 0.012). No significant effects were observed on fasting blood sugar (FBS), diastolic blood pressure (IL-6), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), or triglyceride (TG) levels. Importantly, lipid endpoint analyses were underpowered, with only two RCTs available for most lipid outcomes and a single RCT for triglycerides, representing a significant evidence gap that limits confidence in these findings. Sensitivity analyses confirmed the robustness of results, and publication bias was minimal. Conclusion: Sertraline demonstrates beneficial effects on several cardiometabolic markers, including obesity indices, inflammation, glycemic control, and systolic blood pressure, while showing no significant impact on lipid profiles or diastolic blood pressure. These findings suggest that sertraline may offer added clinical value for patients with depression who are also at increased risk of metabolic and cardiovascular complications. However, because most included trials enrolled participants with comorbidities and moderate-to-severe depression, the generalizability of these results to healthier or lower-risk populations remains uncertain. Moreover, the limited number of trials assessing lipid outcomes highlights a critical need for further well-powered RCTs focusing specifically on lipid profiles to conclusively determine sertraline’s effects on lipid metabolism.