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THE EVIDENCE LIBRARY

Retatrutide and thiamine research library

Every scientific claim on this site traces to one of the fourteen verified records below. Each record shows the citation, the evidence label, what the study supports, what it does not show, its limitations and its conflicts. Bibliographic details were verified against the canonical PubMed record on 2026-08-01.

Author: Bogdan Dicoias · Reviewed by: Panacea Bio Chem Scientific Communications · Published: 2026-08-01 · Last reviewed: 2026-08-01

Retatrutide clinical trials

Published human trialPhase 2 RCT

Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial

Jastreboff AM, Kaplan LM, Frías JP, et al. · New England Journal of Medicine, 389(6):514-526 · 2023

PubMed record ↗ · doi:10.1056/NEJMoa2301972 · PMID 37366315

Design
Randomised, double-blind, placebo-controlled phase 2 trial in obesity
What this study shows
Dose-dependent weight loss up to −24.2% at 48 weeks; adverse events predominantly gastrointestinal and dose-related.
What it does not show
Does not assess micronutrient status, thiamine, or any deficiency endpoint; 48-week phase-2 data only, not long-term safety.
Conflicts
Not recorded in the verified source record (PubMed abstract page, fetched 2026-08-01).

Reta-B1 reading · Anchors what retatrutide does; it says nothing about thiamine — which is precisely the measurement gap Reta-B1 identifies.

Published human trialPhase 2 RCT

Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA

Rosenstock J, Frias J, Jastreboff AM, et al. · The Lancet, 402(10401):529-544 · 2023

PubMed record ↗ · doi:10.1016/S0140-6736(23)01053-X · PMID 37385280

Design
Randomised, double-blind, placebo- and active-controlled phase 2 trial in type 2 diabetes
What this study shows
Confirmed glycaemic and weight efficacy; gastrointestinal adverse events (nausea, vomiting, diarrhoea) in up to ~50% of participants at higher doses.
What it does not show
Does not measure nutritional intake or micronutrient biomarkers; vomiting frequency is reported as an adverse event, not linked to any deficiency outcome.
Conflicts
Not recorded in the verified source record (PubMed abstract page, fetched 2026-08-01).

Reta-B1 reading · Frequent vomiting is the entry point of the historical vomiting → thiamine-depletion pathway; its prevalence on retatrutide is why monitoring matters.

Published human trialRegistrational phase 3

Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial

Bajaj HS, et al. · The Lancet, 407(10546):2402-2413 · 2026

PubMed record ↗ · doi:10.1016/S0140-6736(26)00967-0 · PMID 42250575

Design
Double-blind, randomised phase 3 trial (TRANSCEND-T2D-1), type 2 diabetes
Cases / participants
537 participants
What this study shows
−11.5% to −15.3% bodyweight at 40 weeks (−15.3% at 12 mg); gastrointestinal events the most frequent adverse events, mostly mild-to-moderate.
What it does not show
A type-2-diabetes monotherapy trial — not the obesity TRIUMPH programme; no micronutrient or thiamine endpoints.
Conflicts
Not recorded in the verified source record (PubMed abstract page, fetched 2026-08-01).

Reta-B1 reading · Confirms that substantial, sustained weight reduction with frequent GI symptoms is the realistic use context for any retatrutide-class formulation.

Thiamine deficiency on incretin therapy

Systematic reviewPRISMA systematic review (case-based)

Wernicke’s Encephalopathy Following Semaglutide Treatment for Obesity: A Systematic PRISMA Review of Case-Based Evidence

Bidesie J, Oudman E · Obesity (Silver Spring), online ahead of print · 2026

PubMed record ↗ · doi:10.1002/oby.70256 · PMID 42399213

Design
PRISMA systematic review of published case reports
Cases / participants
6 published cases
What this study shows
All six WE cases after semaglutide for obesity had prolonged GI symptoms and substantial weight loss preceding neurological deterioration; poor outcomes included Korsakoff syndrome and death; authors conclude early parenteral thiamine is essential.
What it does not show
Case-based evidence cannot establish incidence or causation; all cases involve semaglutide, not retatrutide specifically.
Conflicts
Not recorded in the verified source record (PubMed abstract page, fetched 2026-08-01).

Reta-B1 reading · Direct support for treating thiamine status as a first-class formulation question during incretin-class weight loss — while showing the evidence remains case-based.

Published researchPharmacovigilance signal

Glucagon-like peptide-1 receptor agonists and Wernicke encephalopathy: A pharmacovigilance study and literature review

Lev D, Leibowitz A, Lang A, Shlomai G · Clinical Nutrition, 57:106571 · 2026

PubMed record ↗ · doi:10.1016/j.clnu.2025.106571 · PMID 41534460

Design
FAERS disproportionality analysis plus literature review
Cases / participants
15 Wernicke encephalopathy cases in FAERS
What this study shows
Disproportionate reporting of WE with GLP-1 RAs (ROR 2.35, 95% CI 1.38–4.01); 13 of 15 cases involved weight loss, vomiting, appetite loss or malnutrition; long-term sequelae in 7 of 11 cases with follow-up.
What it does not show
Spontaneous-report disproportionality does not prove causality or give absolute risk; reporting bias is possible.
Conflicts
Not recorded in the verified source record (PubMed abstract page, fetched 2026-08-01).

Reta-B1 reading · A signal, not an incidence estimate — but exactly the kind of signal a nutritional-architecture formulation should anticipate rather than ignore.

Published researchPharmacovigilance analysis

Semaglutide-induced Wernicke encephalopathy: a comprehensive analysis

Gras C, De Wit V, Oussedik N, Daclin S, et al. · European Journal of Clinical Nutrition, 79(11):1160-1163 · 2025

PubMed record ↗ · doi:10.1038/s41430-025-01653-7 · PMID 40908328

Design
Case report plus WHO VigiBase disproportionality analysis
Cases / participants
19 WE cases with GLP-1 RAs in VigiBase
What this study shows
68% of cases involved nausea/vomiting or reduced intake; weight loss of 3.5–13.3 kg/month over 3–6 months; disproportionate reporting for semaglutide, tirzepatide and the class as a whole.
What it does not show
Does not demonstrate that prophylactic thiamine prevents these events; pharmacovigilance signal, not an incidence estimate.
Conflicts
Not recorded in the verified source record (PubMed abstract page, fetched 2026-08-01).

Reta-B1 reading · Corroborates that the risk pattern clusters around vomiting, reduced intake and very rapid weight loss — the indirect pathway Reta-B1 addresses.

Published researchCase report

Wernicke Encephalopathy Associated With Semaglutide Use

Sheth K, Garza E, Saju A, Nazir N, Agarwal A · Cureus, 16(6):e61783 · 2024

PubMed record ↗ · doi:10.7759/cureus.61783 · PMID 38975533

Design
Single case report
What this study shows
First widely cited case of non-alcoholic Wernicke encephalopathy temporally associated with semaglutide (37-year-old man; MRI with basal ganglia, thalamic and brainstem signal abnormalities).
What it does not show
A single case without denominator data; cannot establish that semaglutide caused the deficiency rather than unmasking it.
Conflicts
Not recorded in the verified source record (PubMed abstract page, fetched 2026-08-01).

Reta-B1 reading · Hypothesis-generating only — but it opened the question the subsequent reviews and pharmacovigilance analyses then examined systematically.

Nutritional monitoring guidance

Published researchMulti-society advisory

Nutritional priorities to support GLP-1 therapy for obesity: a joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society

Mozaffarian D, Agarwal M, Aggarwal M, et al. · American Journal of Clinical Nutrition, 122(1):344-367 · 2025

PubMed record ↗ · doi:10.1016/j.ajcnut.2025.04.023 · PMID 40450457

Design
Joint expert advisory of four professional societies
What this study shows
Identifies nutritional deficiencies from calorie reduction as a key GLP-1 challenge; advises baseline dietary screening, GI side-effect management and prevention of nutrient deficiencies during therapy.
What it does not show
An expert advisory, not a trial; provides no thiamine-specific dosing or supplementation protocol.
Conflicts
Not recorded in the verified source record (PubMed abstract page, fetched 2026-08-01).

Reta-B1 reading · Institutional backing for the premise that nutritional architecture belongs inside incretin-era formulation thinking.

Published researchConsensus statement

Nutritional, functional, and psychological considerations for incretin-based therapies in adults — an EASO, EFAD, and ECPO Consensus Statement

Dobbie LJ, Tolvanen L, Alves D, et al. · The Lancet Diabetes & Endocrinology, online ahead of print · 2026

PubMed record ↗ · doi:10.1016/S2213-8587(26)00122-1 · PMID 42419343

Design
Consensus statement of European obesity, dietetics and patient organisations
What this study shows
Explicitly proposes pragmatic monitoring of diet quality and micronutrient risk during incretin therapy, and calls for longitudinal research on micronutrient status.
What it does not show
Consensus opinion; does not provide trial evidence that monitoring or supplementation changes outcomes.
Conflicts
Not recorded in the verified source record (PubMed abstract page, fetched 2026-08-01).

Reta-B1 reading · The measurement gap Reta-B1 highlights is now an explicitly stated research priority of the field’s own organisations.

Published researchNarrative review with monitoring framework

Micronutrient risk with GLP-1 receptor and dual incretin agonists in obesity: Mechanistic pathways, clinical signals, and a monitoring framework

Simancas-Racines D, Campuzano-Donoso M, Rossetti G, et al. · Obesity Pillars, 19:100290 · 2026

PubMed record ↗ · doi:10.1016/j.obpill.2026.100290 · PMID 42382663

Design
Narrative review with a proposed monitoring framework
What this study shows
Maps the mechanistic chain (appetite suppression → reduced intake and dietary diversity → GI intolerance → micronutrient vulnerability) and singles out thiamine/Wernicke risk with persistent vomiting or markedly reduced intake; proposes a monitoring algorithm.
What it does not show
Narrative review with a conceptual framework that has not been formally evaluated; states most reported abnormalities are subclinical or indirect.
Conflicts
Not recorded in the verified source record (PubMed abstract page, fetched 2026-08-01).

Reta-B1 reading · Reads almost as the scientific brief for a thiamine-integrated formulation — while remaining a framework awaiting formal evaluation.

Thiamine physiology and deficiency

Systematic reviewLandmark systematic review

Wernicke encephalopathy after bariatric surgery: a systematic review

Aasheim ET · Annals of Surgery, 248(5):714-720 · 2008

PubMed record ↗ · doi:10.1097/SLA.0b013e3181884308 · PMID 18948797

Design
Systematic review of published bariatric Wernicke encephalopathy cases
Cases / participants
84 cases
What this study shows
90% of cases preceded by frequent vomiting (median 21 days); 94% presented within 6 months; 49% had incomplete recovery.
What it does not show
Surgical cohort; does not directly implicate pharmacological (incretin) weight loss, and predates GLP-1 obesity therapy.
Conflicts
Not recorded in the verified source record (PubMed abstract page, fetched 2026-08-01).

Reta-B1 reading · Demonstrates that the vomiting → thiamine-depletion → brain-injury pathway is real and fast when intake collapses — the pathway incretin-era monitoring must interrupt.

Published researchComprehensive reference

Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs

Whitfield KC, Bourassa MW, Adamolekun B, et al. · Annals of the New York Academy of Sciences, 1430(1):3-43 · 2018

PubMed record ↗ · doi:10.1111/nyas.13919 · PMID 30151974

Design
Comprehensive review and roadmap
What this study shows
Reference work on thiamine physiology, the deficiency clinical spectrum and biomarkers — including erythrocyte transketolase (ETKAC) and erythrocyte/whole-blood thiamine diphosphate assays — and the lack of a single agreed biomarker.
What it does not show
Global-health focus (LMIC, beriberi); does not address GLP-1 users or supplementation in obesity pharmacotherapy.
Conflicts
Not recorded in the verified source record (PubMed abstract page, fetched 2026-08-01).

Reta-B1 reading · Defines the measurement toolkit any thiamine-integrated formulation programme must use to justify itself.

Human mechanistic studyBiomarker reference intervals

Establishing reference intervals for thiamine pyrophosphate and pyridoxal 5’-phosphate in whole blood in a Danish cohort using liquid chromatography tandem-mass spectrometry (LC-MS/MS)

Stidsen NM, Bjerg LN, Sandfeld-Paulsen B, et al. · Scandinavian Journal of Clinical and Laboratory Investigation, 84(5):311-316 · 2024

PubMed record ↗ · doi:10.1080/00365513.2024.2392126 · PMID 39146443

Design
Reference-interval study in a healthy Danish blood-donor cohort (LC-MS/MS)
What this study shows
Modern LC-MS/MS reference intervals for whole-blood thiamine pyrophosphate (101–189 nmol/L in healthy adults).
What it does not show
Healthy blood-donor cohort; intervals may not transfer to other populations, assays, or deficiency thresholds in GLP-1 users.
Conflicts
Not recorded in the verified source record (PubMed abstract page, fetched 2026-08-01).

Reta-B1 reading · Supplies the biomarker yardstick for the measurements of thiamine status that the 20 mg inclusion rationale depends on.

Systematic reviewSystematic synthesis (586 cases)

Wernicke-Korsakoff syndrome despite no alcohol abuse: A summary of systematic reports

Oudman E, Wijnia JW, Oey MJ, et al. · Journal of the Neurological Sciences, 426:117482 · 2021

PubMed record ↗ · doi:10.1016/j.jns.2021.117482 · PMID 34000679

Design
Systematic synthesis of non-alcoholic Wernicke-Korsakoff syndrome reports
Cases / participants
586 cases
What this study shows
Vomiting and extreme weight loss are strong predictors of non-alcoholic WKS; authors recommend 500 mg parenteral thiamine three times daily for treatment of established WKS.
What it does not show
Aggregates heterogeneous causes (bariatric, hyperemesis, cancer); treatment-dose recommendation is for established WKS, not prophylaxis, and not specific to incretin users.
Conflicts
Not recorded in the verified source record (PubMed abstract page, fetched 2026-08-01).

Reta-B1 reading · Shows the injury is preventable in principle and devastating when missed — the asymmetry behind taking thiamine seriously early.

How this library is maintained

Records are added only after the canonical source has been fetched and its title, authors and identifiers checked. The last-evidence-search date below changes only when the references have genuinely been rechecked. The selection criteria, correction rules and conflict-of-interest position are set out in the editorial policy.

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