Oral Sodium Butyrate Reduces Weight in Overweight Adults Without Diabetes

BACKGROUND AND AIMS: Butyrate is a microbiota-derived short-chain fatty acid linking colonic fermentation to host metabolism, with systemic availability limited by intestinal utilization and first-pass hepatic metabolism. Whether sodium butyrate (NaBut) supplementation might modulate its circulating levels and metabolic effects is unclear. The aim of this study is to assess whether oral NaBut supplementation improves body weight and metabolic profile in adults with overweight/obesity with or without type 2 diabetes (T2D). METHODS: In this randomized, double-blind, placebo-controlled, parallel-group trial, 46 adults (23 with T2D), aged 30-70 years and BMI 25-39.9 kg/m, were assigned (1:1) to NaBut (1875 mg/day) or placebo for 12 weeks, combined with an identical moderately hypoenergetic diet. Anthropometrics, body composition, fasting metabolic parameters, gastrointestinal symptoms, 7-day continuous glucose monitoring (CGM)-derived metrics, and serum short-chain fatty acids (GC/FID) were evaluated at baseline and week 12. RESULTS: In participants without diabetes, NaBut induced greater reductions in body weight compared with placebo (-7.0 ± 3.0 vs. -3.2 ± 1.6 kg; p = 0.001). In participants with T2D, weight changes did not differ between NaBut and placebo; however, NaBut significantly reduced plasma triglycerides (-0.36 ± 0.47 vs. +0.08 ± 0.30 mmol/L; p = 0.012) and increased time-in-tight-range (TITR; 70-140 mg/dL) by 9 %, independently of weight change. Serum butyrate concentrations increased with NaBut in both cohorts and were associated with weight change in obese people and CGM-derived changes in T2D.. CONCLUSIONS: NaBut supplementation supported weight loss in obesity without diabetes. In T2D, NaBut improved triglyceridemia and CGM-derived glycemic control, largely independent of weight change. TRIAL REGISTRATION NUMBER: NCT07252609 (https://clinicaltrials.gov/study/NCT07252609; ClinicalTrials.gov; 2025-11-17).