Abstract

Tirzepatide, a once weekly GIP/GLP-1 receptor agonist in development for T2D, demonstrated superior glycemic control in the Phase 3 SURPASS clinical trial program. This post-hoc analysis assessed glycemic control with tirzepatide in participants stratified by baseline (BL) HbA1c (≤8.5%, >8.5%) . Mean change from BL in HbA1c was assessed in tirzepatide-treated participants (5, or 15 mg) from SURPASS-1 (monotherapy) , SURPASS-2 (add-on to MET) , SURPASS-3 (add on to MET ± SGLT2i) , SURPASS-4 (add-on to MET, SGLT2i, or sulfonylurea) and SURPASS-5 (add-on to insulin glargine ± MET) at trial endpoints (40 or 52 weeks) . Safety was also presented. Treatment comparisons were estimated using data while participants were on treatment and without rescue medications (efficacy estimand) . Across each SURPASS trial, ranges in mean BL HbA1c were 7.94-8.52%, mean BMI were 31.9-34.2 kg/m2 and mean diabetes duration were 4.7-13.3 years. At trial endpoints, HbA1c reductions from BL ranged from 1.55-2.14% in the BL HbA1c ≤8.5% subgroup and 2.70-3.46% in the BL HbA1c >8.5% subgroup (Table) . Gastrointestinal side effects were similar to those reported in the incretin class and hypoglycemic events (blood glucose <54 mg/dL or severe) were low. In conclusion, significant and clinically meaningful HbA1c reductions were observed with tirzepatide, irrespective of BL HbA1c. Disclosure G.Aleppo: Consultant; Insulet Corporation, Research Support; AstraZeneca, Dexcom, Inc., Eli Lilly and Company, Fractyl Health, Inc., Insulet Corporation, Novo Nordisk, Speaker's Bureau; Dexcom, Inc. C.De block: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk, Research Support; Indigo Diabetes, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk. J.A.Levine: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. E.Gomez-valderas: Employee; Lilly, Stock/Shareholder; Lilly. B.D.Benneyworth: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company

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