Targeting weight loss and blood glucose control with oral sodium butyrate in overweight/obese adults with and without type 2 diabetes: A proof-of-concept randomized controlled trial

SummaryBackground and AimsButyrate 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).MethodsIn this randomized, double-blind, placebo-controlled, parallel-group trial, 46 adults (23 with T2D), aged 30–70 years and BMI 25–39.9 kg/m2, 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.ResultsIn 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..ConclusionsNaBut 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).