864-P: Glycemic Control across eGFR Categories with the Dual SGLT1 and 2 Inhibitor Sotagliflozin in SCORED
Authors: INZUCCHI SILVIO E. , BHATT DEEPAK L. , PITT BERTRAM , SZAREK MICHAEL , CANNON CHRISTOPHER P. , LEWIS JULIA B. , RIDDLE MATTHEW C. , KOSIBOROD MIKHAIL N. , CHERNEY DAVID , DWYER JAMIE P. , SCIRICA BENJAMIN M. , BAILEY CLIFFORD J. , BANKS PHILLIP L. , DIAZ RAFAEL , RAY KAUSIK K. , UDELL JACOB A. , LOPES RENATO D. , LEITER LAWRENCE A. , STEG PHILIPPE G. ,   SCORED INVESTIGATORS
Published: May 2022

In cardiovascular (CV) outcome trials (OT) of glucose-lowering medications (GLM) , glycated hemoglobin (A1c) is typically treated according to local standard of care, with aim of glycemic equipoise between the randomized groups. However, in SGLT inhibitor CVOTs, larger A1c reductions are consistently seen in the active therapy vs. placebo (PBO) groups, since the former has access to an additional class of GLM. SCORED was a multicenter, double-blind, placebo-controlled CVOT of the dual SGLT1 and 2 inhibitor sotagliflozin (SOTA) , which may have preserved antihyperglycemic effects even in those with advanced chronic kidney disease (CKD.) We assessed the association between A1c lowering and assignment to SOTA vs. PBO in the overall trial population and across various pre-specified subgroups, including CKD categories. 10,584 type 2 diabetes (T2D) (A1c ≥7%) patients with CKD (eGFR 25-60 mL/min/1.73 m2) and increased CV risk were randomized to SOTA vs. PBO and followed for a median of 15.9 months. We previously reported that the risk for the primary composite outcome of total CV deaths and hospitalizations or urgent visits for heart failure was reduced by 26% in the SOTA group (p&lt;0.001) . In the overall population, from a baseline A1c of 8.7%, the least-squares mean change in A1c was -0.60% with SOTA and -0.17% with placebo (mean difference [95% CI] = -0.42% [-0.47, -0.38]; p&lt;0.0001) . Differences were larger with increasing baseline A1C: &lt;8%: -0.31%; 8-&lt;9%: -0.40%; and ≥9%: -0.57% (all p&lt;0.0001) . The association between SOTA use and A1c lowering vs. placebo was consistent across strata of baseline eGFR, including those with CKD stage 4 (eGFR&gt;45, 30-&lt;45, and &lt;30: -0.47%. -0.38%, and -0.31%, respectively [all p&lt;0.001]) . These results were similarly consistent across age, sex, race/ethnicity, age, and BMI subgroups. In SCORED, SOTA consistently reduced A1c across all pre-specified subgroups, including patients with the lowest baseline eGFR, possibly reflecting SOTA’s dual mechanism of action.

Disclosure
S.E.Inzucchi: Advisory Panel; Abbott Diagnostics, ESPERION Therapeutics, Inc., vTv Therapeutics, Consultant; Merck & Co., Inc., Pfizer Inc., Other Relationship; AstraZeneca, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Novo Nordisk. J.P.Dwyer: Consultant; Akebia Therapeutics, Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Cincor, Inc, CSL Behring, FibroGen, Inc., Reata Pharmaceuticals, Inc., Sanofi, Tricida, Inc. B.M.Scirica: Consultant; Allergan, Boehringer Ingelheim International GmbH, ESPERION Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Novo Nordisk, Research Support; Better Therapeutics, Eisai Co., Ltd., Merck & Co., Inc., Novo Nordisk, Pfizer Inc., Stock/Shareholder; Heath At Scale. C.J.Bailey: None. P.L.Banks: Employee; Lexicon Pharmaceuticals, Inc. R.Diaz: None. K.K.Ray: Consultant; Abbott, AstraZeneca, Cargene, CSL Behring, Daiichi Sankyo, Eli Lilly and Company, ESPERION Therapeutics, Inc., GlaxoSmithKline plc., Kaleido, Kowa Company, Ltd., New Amsterdam Pharma, Novartis Pharmaceuticals Corporation, Pfizer Inc., Regeneron Pharmaceuticals Inc., Roche Diagnostics, The Medicines Company, Research Support; Amgen Inc., Daiichi Sankyo, Regeneron Pharmaceuticals Inc., Sanofi, Speaker's Bureau; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Medscape, Novartis Pharmaceuticals Corporation, Novo Nordisk, Sanofi, Viatris Inc., Stock/Shareholder; Cargene, PEMI31. J.A.Udell: Consultant; Boehringer Ingelheim International GmbH, Novartis AG, Sanofi, Other Relationship; GlaxoSmithKline plc., Sanofi, Research Support; Amgen Inc., Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research & Development, LLC. R.D.Lopes: Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Daiichi Sankyo, GlaxoSmithKline plc., Medtronic, Pfizer Inc., Portola Pharmaceuticals, Inc., Other Relationship; Bristol-Myers Squibb Company, Sanofi, Research Support; Medtronic, Pfizer Inc. L.A.Leiter: Advisory Panel; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi, Research Support; AstraZeneca, Bayer AG, Lexicon Pharmaceuticals, Inc., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Servier Laboratories. P.G.Steg: Advisory Panel; AstraZeneca, Bristol-Myers Squibb Company, Board Member; Novartis AG, Consultant; Amarin Corporation, Amgen Inc., Bayer AG, Idorsia Pharmaceuticals Ltd., Lexicon Pharmaceuticals, Inc., PhaseBio Pharmaceuticals, Inc., Sanofi. D.L.Bhatt: Research Support; Afimmune Limited, Amarin Corporation, Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Chiesi USA, Inc., Lexicon Pharmaceuticals, Inc., Lilly, Novartis AG, Sanofi. Scored investigators: n/a. B.Pitt: Advisory Panel; Merck & Co., Inc., Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Vifor Pharma

Funding
Sanofi/Lexicon