Changes in liver and abdominal fat in tirzepatide-treated patients achieving normoglycaemia in the SURPASS-3 MRI substudy

Tirzepatide (TZP), a novel, once-weekly GIP/GLP-1 receptor agonist, significantly reduced liver fat content (LFC) and volumes of visceral and abdominal subcutaneous adipose tissue (VAT and ASAT) vs insulin degludec in a subpopulation of patients in the SURPASS-3 phase 3 trial. This post-hoc analysis evaluated changes from baseline to Week 52 in these outcomes and other clinical and laboratory parameters in TZP-treated patients achieving or not achieving normoglycemia (HbA1c <5.7%) at Week 52. LFC, VAT and ASAT volumes were assessed with MRI prior to randomization and at Week 52 in insulin-naïve patients with type 2 diabetes inadequately controlled on metformin with/without SGLT-2i and fatty liver index ≥60 at baseline. Analyses used pooled data from all TZP arms (5, 10, and 15 mg). Patients achieving HbA1c <5.7% were slightly younger and had lower baseline HbA1c and VAT vs those not achieving HbA1c <5.7%. Substantial reductions in LFC, VAT and ASAT volumes, weight, HbA1c, and overall improvement in lipids profile were observed in both subsets of patients (Table). Among patients achieving HbA1c <5.7% and ≥5.7%, respectively, 56% and 27% achieved LFC <6%, and 91% and 64% achieved ≥30% reduction in LFC. In summary, in TZP-treated patients, changes in LFC, VAT and ASAT, and lipids were more pronounced in those achieving normoglycemia. Disclosure Á.Rodríguez: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. K.Cusi: Consultant; Poxel SA, Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns, Research Support; Echosens, Inventiva, LabCorp, Zydus. A.Gastaldelli: Advisory Panel; Pfizer Inc., Novo Nordisk, Merck Sharp & Dohme Corp., Boehringer Ingelheim International GmbH, Consultant; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Fractyl Health, Inc., Merck Sharp & Dohme Corp., Other Relationship; Pfizer Inc., Speaker's Bureau; Eli Lilly and Company. C.Nicolay: Employee; Eli Lilly and Company. A.Torcello-gomez: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. L.Fernandez lando: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company