Effect of SY009, a novel SGLT1 inhibitor, on the plasma metabolome and bile acids in patients with type 2 diabetes mellitus
Abstract
Context: As a novel SGLT1 inhibitor, SY-009 has been preliminarily confirmed in a phase Ib clinical study for its ability to reduce postprandial blood glucose in patients with type 2 diabetes mellitus (T2DM). However, the effects of SY-009 on human plasma metabolomics are still unknown.
Objective: This study aimed to explore the effects of SY-009 on plasma metabolomics in patients with T2DM and the potential metabolic regulatory mechanism involved.
Study design: In the phase Ib study, a total of 50 participants with T2DM were enrolled and randomly assigned to the 0.5 mg BID, 1 mg BID, 2 mg BID, 1 mg QD, and 2 mg QD dose groups, with a 4:1 random allocation within each group to receive either the SY-009 capsule or placebo. We conducted untargeted and targeted metabolomics analyses on plasma samples from the phase Ib clinical study.
Results: Untargeted metabolomics revealed that, after SY009 treatment, there were differences in metabolic pathways, including primary bile acid biosynthesis; biosynthesis of unsaturated fatty acid; steroid hormone biosynthesis; purine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis. In particular, the increase in bile acid-related metabolites in the 2 mg BID group was significantly greater than that in the placebo group, and unsaturated fatty acid-related metabolites decreased in both the 2 mg BID group and the placebo group, but there was no significant difference between the two groups. After comprehensive consideration, bile…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 50 participants or records.
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