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Record W4399684039 · doi:10.2337/db24-897-p

897-P: Insulin-Sensitizing Effects of Efruxifermin Improve Glycemic Control in Patients with MASH and Type 2 Diabetes

2024· article· en· W4399684039 on OpenAlexaboutno aff
Kathryn Jean Lucas, S. Harrison, Doreen Chan, Erik J. Tillman, A. W. Moulton, Brittany de Temple, Arian Zari, RESHMA SHRINGARPURE, Tim Rolph, Andrew Cheng, Kitty Yale

Bibliographic record

VenueDiabetes · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicFibroblast Growth Factor Research
Canadian institutionsnot available
Fundersnot available
KeywordsMedicineGlycemicType 2 diabetesSteatohepatitisInsulinInternal medicineDiabetes mellitusInsulin resistanceEndocrinologyCirrhosisGastroenterologyFatty liverDisease

Abstract

fetched live from OpenAlex

Introduction & Objective: In phase 2 studies, efruxifermin (EFX), a long-acting bivalent Fc-FGF21 analog, significantly reduced steatohepatitis and fibrosis in patients with metabolic dysfunction-associated steatohepatitis (MASH). Many patients with MASH have type 2 diabetes (T2D), which is increasingly treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs). We investigated the effects of EFX in patients with T2D, including those being treated with GLP-1RAs. Methods: The effects of EFX on markers of insulin sensitivity and glycemic control were studied in 5 independent cohorts of patients with T2D and MASH with liver fibrosis, ranging from F1 to F4 (compensated cirrhosis). EFX treatment ranged from 12 to 36 weeks. Endpoints included changes in markers of glucose metabolism and insulin sensitivity, lipoprotein profile, steatohepatitis, and fibrosis, as well as use of T2D medications. Results: EFX consistently improved markers of insulin sensitivity and glucose metabolism on top of stable T2D therapies, including GLP-1RA. EFX was also associated with a trend towards weight loss. Markers of liver injury, steatohepatitis, and fibrosis were improved consistently by EFX, even in patients on stable GLP-1RA therapy. EFX was safe and well tolerated in all trials; the most common AEs were mild-moderate gastrointestinal events. Conclusions: EFX has consistently improved markers of whole-body glucose and lipid metabolism in patients with MASH and T2D, even on top of stable T2D medications including GLP-1RA. EFX-mediated insulin sensitization may potentiate effects of insulin or insulin secretagogues, possibly enabling patients to reduce use of insulin and/or other T2D medications to mitigate weight gain, incidence of hypoglycemia, or other side effects. Disclosure K.J. Lucas: Research Support; Akero Therapeutics, Inc. S.A. Harrison: Other Relationship; Akero Therapeutics, Inc. Consultant; 89bio, Inc., Agilos Therapeutics. Other Relationship; Altimmune Inc. Advisory Panel; Arrowhead Pharmaceuticals, Inc. Consultant; Asteroid Therapeutics, Bluejay Therapeutics. Research Support; Bristol-Myers Squibb Company. Consultant; BOEHRINGER INGELHEIM PHARMA, INC, Boxer Capital. Advisory Panel; Chronwell Inc. Consultant; Corcept Therapeutics, ECCOGENE, INC, DEXCOM, INC. Advisory Panel; ECHOSENS NORTH AMERICA, INC. Consultant; Enyo Pharma. Other Relationship; GALECTIN THERAPEUTICS, INC. Consultant; GALECTO, INC, HEPAGENE THERAPEUTICS. Other Relationship; HEPION PHARMACEUTICALS, INC, Gilead Sciences, Inc. Consultant; GlaxoSmithKline plc. Other Relationship; Hepta Bio. Consultant; HISTOINDEX PTE. LTD. Advisory Panel; Humana. Other Relationship; Madrigal Pharmaceuticals, Inc., Intercept Pharmaceuticals, Inc. Advisory Panel; Inventiva Pharma. Other Relationship; Ionis Pharmaceuticals, Medpace. Stock/Shareholder; MGGM THERAPEUTICS LLC. Consultant; NEUROBO PHARMACEUTICALS INC. Other Relationship; NGM BIOPHARMACEUTICALS, INC, NORTHSEA THERAPEUTICS B.V., Novo Nordisk. Research Support; Pfizer Inc. Consultant; PIPER SANDLER & CO. Other Relationship; POXEL. Consultant; Regeneron Pharmaceuticals Inc. Other Relationship; Sagimet Biosciences, Sonic Incytes. Consultant; Takeda Canada. Other Relationship; Terns Pharmaceuticals. Consultant; TRAMONTANE THERAPEUTICS INC (Kriya). Other Relationship; Viking Therapeutics. Consultant; CALIMETRIX, LLC. D. Chan: Employee; Akero Therapeutics, Inc. E.J. Tillman: Employee; Akero Therapeutics, Inc. Stock/Shareholder; Akero Therapeutics, Inc. A. Moulton: Employee; Akero Therapeutics, Inc. Stock/Shareholder; Akero Therapeutics, Inc. B. de Temple: Employee; Akero Therapeutics, Inc. Stock/Shareholder; Akero Therapeutics, Inc. A. Zari: Employee; Akero Therapeutics, Inc. Stock/Shareholder; Akero Therapeutics, Inc. R. Shringarpure: Employee; Akero Therapeutics, Inc. Stock/Shareholder; Akero Therapeutics, Inc. T. Rolph: Stock/Shareholder; Akero Therapeutics, Inc., Pfizer Inc. A. Cheng: Employee; Akero Therapeutics, Inc. K. Yale: Employee; Akero Therapeutics, Inc. Funding Akero Therapeutics Inc

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.143
Threshold uncertainty score0.512

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.002
GPT teacher head0.197
Teacher spread0.195 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2024
Admission routes1
Has abstractyes

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