Effects of Non-Nutritive Sweeteners on Weight Loss and Maintenance, Metabolic Improvement, and Appetite Regulation in Weight Management Programs: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

CONTEXT: Achieving and maintaining weight loss remains a clinical challenge, prompting interest in the potential role of non-nutritive sweeteners (NNSs) in weight management. OBJECTIVE: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effects of NNSs on weight loss, weight maintenance, metabolic outcomes, and appetite regulation within weight-management programs. DATA SOURCES: We searched MEDLINE, Web of Science, Ovid, Embase, and Cochrane databases up to December 2023. DATA EXTRACTION: Effect sizes for body weight and metabolic parameters were expressed as mean differences (MDs), and standardized mean differences (SMDs) were used for hunger scores. DATA ANALYSIS: NNSs showed comparable efficacy with that of control interventions in promoting weight reduction within weight-management programs. However, subgroup analyses revealed significantly greater weight loss with NNSs in the "mixed consumption" group (trials with unquantified baseline NNS exposure; MD = -0.89 kg, 95% CI: -1.61 to -0.17) and the "aspartame" group (trials using aspartame as the sole NNS; MD = -1.03 kg, 95% CI: -2.01 to -0.05). Regarding metabolic outcomes, NNSs had no significant benefits over controls in improving lipid profiles. For glucose metabolism, insulin levels decreased less in the NNS group compared with the control group (MD = 13.80 pmol/L, 95% CI: 2.67 to 24.93), indicating that NNSs may be less effective in improving insulin sensitivity during weight management. In terms of appetite regulation, NNSs had no significant impact on hunger during the weight-maintenance phase; however, during the weight-loss phase, NNS consumption led to a reduction in hunger compared with the control groups (SMD = -0.16, 95% CI: -0.30 to -0.01). CONCLUSIONS: NNSs may enhance weight loss in "mixed consumption" and "aspartame" subgroups but do not offer clear benefits for lipid or glucose metabolism improvement. They may help reduce appetite during the weight-loss phase, though further evidence is needed.