Selected publication milestones, not an exhaustive history or discovery priority claim.
2006 — Human cyclosporin interaction work shows dose-dependent exposure effects, an early constraint on simple supplement-safety claims. Original PMID16541194.
2008 — A three-month placebo-controlled T2D/dyslipidemia trial reports HbA1c and glucose benefit with ordinary berberine. Original PMID18397984.
2008 — The metformin pilot and uncontrolled add-on component motivate clinical research while leaving noninferiority and treatment attribution unresolved. Original PMID18442638.
2008 — Acute secretion inhibition and later cell response show that dose, glucose state and timing matter for mechanism narratives. Original PMID18511510.
2010 — Patient metabolomics proposes free-fatty-acid involvement but is conservatively grouped with related earlier efficacy work. Original PMID20298851.
2012 — Repeated-dose healthy-human CYP probe testing verifies drug-interaction potential rather than assuming inert supplement exposure. Original PMID21870106.
2015 — A direct glutathione trial establishes body-store engagement, providing ingredient context without testing a triple stack. Original PMID24791752.
2015 — Animal microbial conversion/absorption experiments propose an exposure route; broad antibiotic perturbation does not isolate clinical human mediation. Original PMID26174047.
2020 — PREMOTE supplies a verified concealed twelve-week T2D placebo comparison and a separate microbial hypothesis under common antibiotic pretreatment. Original PMID33024120.
2021 — NMN improves measured muscle insulin sensitivity in prediabetic women, a component-specific result without combination evidence. Original PMID33888596.
2021 — Mouse KCNH6 loss and a healthy-human acute clamp narrow a secretion mechanism; the attached correction changes an author name only. Original PMID34556670.
2022 — A PREMOTE lipid secondary analysis illustrates why new mechanistic resolution is not a new independent efficacy trial. Original PMID34923903.
2023 — Short NMN physiology produces NAD and selected risk-factor changes while several functional/metabolic endpoints remain null. Original PMID36740954.
2024 — An older-adult NMN trial has a null primary stepping endpoint alongside selected secondary walking/sleep signals. Original PMID38789831.
2025 — A distinct BUDCA formulation produces dose-related twelve-week T2D HbA1c benefit while weight stays stable. Original PMID40029660.
2026 — A six-month ordinary-berberine obesity/MASLD trial is null for adiposity and glycemic measures in diabetes-free adults, limiting broad weight-loss extrapolation. Original PMID41543854.
2026 — Drug-response signature MR generates cardiometabolic hypotheses without directly instrumenting oral exposure or replacing clinical event trials. Original PMID41882153.
Durable ordinary-berberine efficacy and safety beyond short T2D trials under contemporary unchanged standard care
Role of common antibiotic pretreatment and baseline microbial ecology in the PREMOTE response
Exposure/product standardization and translation between ordinary berberine, BUDCA and botanical bundles
Unique chronic human mediation versus simultaneous gut, secretion, receptor and mitochondrial effects
Direct modern GLP-1 equivalence for specified weight and cardiometabolic outcomes
Exact triple-stack trials and component-dismantling evidence with meaningful functional outcomes
Drug interactions, formulation variability and all-comer tolerability beyond selected short-term cohorts
Run a multisite, baseline-stratified, double-blind trial of chemically verified ordinary oral berberine versus matching placebo added to unchanged standard T2D care, with prespecified twelve-month glycemic durability and adverse-event outcomes. Include strata for baseline HbA1c, disease duration and fixed co-medication; avoid routine antibiotic pretreatment or randomize that factor separately if mechanistically essential. Add prespecified pathway measurements and an orthogonal mediator-dissociation component rather than declaring correlated microbiome changes necessary. Evaluate GLP-1 equivalence and the exact triple stack in separate properly controlled trials.