Effect of Sevelamer and B. longum on Insulin Sensitivity in Participants With Obesity: A Randomized Clinical Trial.

2026-05-15
Obesity (Silver Spring, Md.) 34(7)
- Eric Baeuerle
- Manpreet K Semwal
- Jia Nie
- Ning Zhang
- Hanyu Liang
- Vinutha Ganapathy
- Nattapol Sathavarodom
- Roman Fernandez
- Chen-Pin Wang
- Sara Espinoza
- Qunfeng Dong
- Xiang Gao
- Zhen Yang
- Aleksandar Kostic
- Nicolas Musi

PubMed: 42141362
DOI: 10.1002/oby.70224

Study Design

Type: Randomized Controlled Trial (RCT)
Population: 22 lean and 28 participants with obesity
Methods: randomized, double-blind, placebo-controlled, three-arm parallel-group trial; sevelamer, synbiotic (oligofructose plus Bifidobacterium longum Rosell-175), or placebo three times a day for 4 weeks
Blinding: Double-blind
Duration: 4 weeks

Objective

This study evaluated whether two interventions with putative lipopolysaccharide (LPS)-lowering properties, the phosphate binder sevelamer or a synbiotic, improve insulin sensitivity in humans.

Methods

We conducted a randomized, double-blind, placebo-controlled, three-arm parallel-group trial. Twenty-two lean and twenty-eight participants with obesity completed the trial. Participants were randomized to: (1) sevelamer; (2) synbiotic (oligofructose plus Bifidobacterium longum Rosell-175); or (3) placebo, three times a day for 4 weeks. The primary outcome was change in peripheral insulin sensitivity (M) assessed by hyperinsulinemic (60 mU/m² min) euglycemic clamp versus placebo.

Results

In participants with obesity, sevelamer improved the M (+2.176 [0.314, 4.038] mg/kg min vs. placebo; p = 0.022) and lowered LDL-C (-29.675 [-53.794, -5.556] mg/dL vs. placebo; p = 0.016). Synbiotic had no effect on insulin sensitivity or lipids in either group. No changes in markers of endotoxemia were observed with any intervention. Sevelamer increased plasma levels of metabolites linked to improved glucose and lipid metabolism, such as bile acids, amino acids (citrulline, betaine), NAD+ precursors (trigonelline), and xenobiotics (genistein, umbelliferone).

Conclusions

Sevelamer improves insulin sensitivity and LDL-C in participants with obesity. Further investigation is warranted to elucidate sevelamer's metabolic mechanisms, potentially involving the mediation of bile acids and other host-microbiome-derived metabolites.

Trial registration

ClinicialTrials.gov NCT02127125.