Efficacy of Sotagliflozin in Adults With Type 2 Diabetes in Relation to Baseline Hemoglobin A1c

Rahul Aggarwal; Deepak L Bhatt; Michael Szarek; Christopher P Cannon; Darren K McGuire; Silvio E Inzucchi; Renato D Lopes; Michael J Davies; Phillip Banks; Bertram Pitt; Philippe Gabriel Steg

doi:10.1016/j.jacc.2023.08.050

Efficacy of Sotagliflozin in Adults With Type 2 Diabetes in Relation to Baseline Hemoglobin A1c

J Am Coll Cardiol. 2023 Nov 7;82(19):1842-1851. doi: 10.1016/j.jacc.2023.08.050.

Authors

Affiliations

¹ Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massachusetts, USA.
² Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address: DLBhattMD@post.Harvard.edu.
³ CPC Clinical Research and University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; State University of New York Downstate School of Public Health, Brooklyn, New York, USA.
⁴ University of Texas Southwestern Medical Center and Parkland Health and Hospital System, Dallas, Texas, USA.
⁵ Yale University School of Medicine, New Haven, Connecticut, USA.
⁶ Duke University School of Medicine, Durham, North Carolina, USA.
⁷ Lexicon Pharmaceuticals, Inc, the Woodlands, Texas, USA.
⁸ University of Michigan, Ann Arbor, Michigan, USA.
⁹ Université Paris-Cité, INSERMU1148 and AP-HP Hopital Bichat, Paris, France; French Alliance for Cardiovascular Trials, Paris, France.

PMID: 37914514
DOI: 10.1016/j.jacc.2023.08.050

Abstract

Background: The SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) and SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) trials demonstrated that sotagliflozin, an SGLT1 and SGLT2 inhibitor, improves outcomes in individuals with type 2 diabetes who have heart failure (HF) or kidney disease.

Objectives: We assessed the efficacy of sotagliflozin on HF clinical outcomes in individuals with differing baseline glycosylated hemoglobin (HbA1c) levels.

Methods: We included all adults from SCORED and SOLOIST-WHF. The primary outcome was a composite of cardiovascular death, hospitalizations for HF, and urgent visits for HF. The efficacy of sotagliflozin compared with placebo was evaluated by baseline HbA1c using competing-risk marginal proportional hazards models.

Results: We identified 11,744 adults. Individuals with HbA1c ≤7.5% experienced the primary outcome at a lower rate in the sotagliflozin group (11.2 per 100 person-years) than the placebo group (15.5 per 100 person-years) (HR: 0.73; 95% CI: 0.57-0.93). Similarly, individuals with HbA1c of 7.6% to 9.0% experienced the primary outcome at a lower rate in the sotagliflozin group (7.3 per 100 person-years) than the placebo group (9.4 per 100 person-years) (HR: 0.77; 95% CI: 0.63-0.96). These findings were also consistent among individuals with HbA1c >9.0%, with a primary outcome rate in the sotagliflozin group (7.8 per 100 person-years) that was lower than the placebo group (11.6 per 100 person-years) (HR: 0.65; 95% CI: 0.50-0.84). The efficacy of sotagliflozin was consistent by baseline HbA1c level (P for interaction = 0.58).

Conclusions: In individuals with type 2 diabetes and either HF or kidney disease, sotagliflozin reduced HF outcomes irrespective of baseline HbA1c.

Keywords: heart failure; hemoglobin a1c; sodium–glucose cotransporter 1 inhibitors; sodium–glucose cotransporter 2 inhibitors; sotagliflozin; type 2 diabetes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Diabetes Mellitus, Type 1* / drug therapy
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / drug therapy
Glycated Hemoglobin
Heart Failure*
Humans
Kidney Diseases*

Substances

Glycated Hemoglobin
(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol