17-OR: ADA Presidents' Select Abstract: Effects of Tirzepatide vs. Insulin Glargine 100 U/mL on Kidney Outcomes in Participants with Type 2 Diabetes in SURPASS-4
Authors: HEERSPINK HIDDO L. , SATTAR NAVEED , PAVO IMRE , HAUPT AXEL , DUFFIN KEVIN L. , YANG ZHENGYU , WIESE RUSSELL , TUTTLE KATHERINE R. , CHERNEY DAVID 
Published: May 2022

Tirzepatide (TZP, 5, 10, 15 mg/week) , a dual GIP/GLP-1 receptor agonist, reduced HbA1c levels more than titrated daily insulin glargine (iGlar) in people inadequately controlled on oral diabetes treatments with type 2 diabetes (T2D) and high cardiovascular risk (median study duration 85 weeks) . Here, we compared progression to pre-specified kidney endpoints between TZP and iGlar. Composite kidney outcomes in SURPASS-4 were analysed: endpoint 1 (eGFR [CKD-EPI] decline ≥40% from baseline, renal death, progression to ESRD, new onset macroalbuminuria) and endpoint 2 (endpoint 1 without new onset macroalbuminuria) . Data were examined within the entire study population, and in subgroups defined by baseline SGLT2i use, UACR ≥30 mg/g, eGFR &lt;60 mL/min/1.73m2 and in those at high risk for kidney related outcomes, defined as eGFR &lt;75 mL/min per 1.73 m2 and macroalbuminuria, or eGFR &lt;45 mL/min per 1.73 m2. At baseline, participants (N=1995, age 63.6 years, HbA1c, 8.5%) had a mean eGFR of 81.3 mL/min per 1.73 m2; 17% had eGFR &lt;60 mL/min per 1.73 m2, 28% microalbuminuria (UACR 30-300 mg/g) and 8% macroalbuminuria (UACR &gt;300 mg/g) . During the follow-up to 1weeks, TZP participants experienced significantly fewer renal outcomes, especially new onset of macroalbuminuria versus iGlar (Table) . In people with T2D and high cardiovascular risk, TZP reduced markers of diabetic kidney disease risk.

Disclosure
H.L.Heerspink: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Chinook Therapeutics Inc., CSL Behring, Gilead Sciences, Inc., Goldfinch Bio, Inc., Janssen Research & Development, LLC, Mitsubishi Tanabe Pharma Corporation, Mundipharma, Traveere Pharmaceuticals, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. N.Sattar: Consultant; Afimmune Limited, Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Novartis Pharmaceuticals Corporation, Roche Diagnostics. I.Pavo: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. A.Haupt: Employee; Lilly, Stock/Shareholder; Lilly. K.L.Duffin: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company, Pfizer Inc. Z.Yang: Employee; Eli Lilly and Company. R.Wiese: Employee; Eli Lilly and Company. K.R.Tuttle: Advisory Panel; Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Consultant; AstraZeneca, Eli Lilly and Company, Research Support; Bayer AG, Goldfinch Bio, Inc., Novo Nordisk, Travere. D.Cherney: Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research & Development, LLC, Lilly, Maze, BMS, CSL-Behring, Merck, Otsuka, Novartis and Novo-Nordisk , Mitsubishi Tanabe Pharma Corporation, Sanofi, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk.

Funding
Eli Lilly and Company