An Oral Heat-Inactivated Postbiotic Increases Endogenous GLP-1 and Promotes Weight Loss in Adults with Overweight or Obesity: A Randomized Placebo-Controlled Trial

Background: Heat-inactivated postbiotics derived from Lactiplantibacillus plantarum have been proposed to support weight management and metabolic health by acting on the gut-metabolic axis, including endogenous glucagon-like peptide-1 (GLP-1) signaling. resM is an orally delivered formulation combining heat-inactivated L. plantarum RSB11 (RSB11-HI) with vitamin D3, vitamin B12, chromium picolinate, white mulberry (Morus alba) leaf, and fenugreek (Trigonella foenum-graecum) seed extracts. We tested the effects of resM on body weight and a panel of metabolic outcomes in adults with overweight or obesity. Methods: In a randomized, double-blind, placebo-controlled, parallel-group trial (NCT06911073), 80 adults with overweight or obesity were allocated 1:1 to oral resM or matched placebo for 8 weeks. The trial was conducted in a fully remote, direct-to-consumer setting. The primary outcome was absolute change in body weight at the final scheduled weekly assessment, Week 7, corresponding to completion of the 8-week intervention. Secondary outcomes included body-mass index; fasting insulin, HbA1c, and HOMA-IR; serum active GLP-1; strain-specific stool quantitative PCR for L. plantarum RSB11; food cravings measured using the Food Craving Questionnaire-Trait-reduced; depressive symptoms measured using the PHQ-9; safety laboratory measures; and adverse-event surveillance. Between-group differences were evaluated using independent-samples t-tests and baseline-adjusted ANCOVA, and within-group changes were evaluated using paired tests. Results: Body weight decreased by 2.6 kg, or 3.0%, in the resM group and increased by 0.5 kg, or 0.6%, in the placebo group. Food-craving scores fell by 15.1 points within the resM arm during the 8-week intervention (p<0.001), as did depression scores. Active GLP-1 approximately doubled among participants treated with resM and increased more than in the placebo group. Serum GLP-1 levels correlated with L. plantarum RSB11 levels in stool samples in the resM arm. Safety laboratory values remained within reference ranges, gastrointestinal symptoms were reported more frequently with placebo than with resM, and no serious adverse events were reported in either group. Conclusions: Over 8 weeks, resM produced clinically meaningful weight loss within the intervention group and compared with placebo, together with reductions in food cravings and depression scores and an approximately two-fold increase in active GLP-1. Larger and longer-duration trials are needed to confirm the persistence and generalizability of these findings.