Related Experiment Video
Updated: Nov 30, 2025
Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure
Deepak L Bhatt1, Michael Szarek1, P Gabriel Steg1
1From Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston (D.L.B., C.P.C.); Colorado Prevention Center Clinical Research and Department of Medicine, Division of Cardiovascular Medicine, University of Colorado Anschutz Medical Campus, Aurora (M.S.); State University of New York Downstate School of Public Health, Brooklyn (M.S.); Université de Paris, French Alliance for Cardiovascular Trials, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, INSERM Unité 1148 (P.G.S.), and Paris Sorbonne University and Groupe Hospitalier Paris Saint Joseph (M.K.), Paris; Li Ka Shing Knowledge Institute (L.A.L., S.V.) and the Divisions of Endocrinology and Metabolism (L.A.L.) and Cardiac Surgery (S.V.), St. Michael's Hospital, and the Departments of Medicine and Nutritional Sciences (L.A.L) and Surgery and Pharmacology and Toxicology (S.V.), University of Toronto, Toronto; University of Texas Southwestern Medical Center and Parkland Health and Hospital System, Dallas (D.K.M.), and Lexicon Pharmaceuticals, The Woodlands (P.L.) - both in Texas; Vanderbilt University, Nashville (J.B.L.); the Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health and Science University, Portland (M.C.R.); University of Groningen-University Medical Center Groningen, Groningen, the Netherlands (A.A.V); Azienda Socio Sanitaria Territoriale Spedali Civili and University of Brescia, Brescia, Italy (M.M.); Karolinska Institutet, Stockholm (L.H.L.); Yale University, New Haven, CT (J.M.T.); Georgetown University, Washington, DC (C.S.W.); Wroclaw Medical University, Wroclaw, Poland (P.P.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (R.D.L.); and the University of Michigan, Ann Arbor (B.P.).
Background:
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure or death from cardiovascular causes among patients with stable heart failure. However, the safety and efficacy of SGLT2 inhibitors when initiated soon after an episode of decompensated heart failure are unknown.
Methods:
We performed a multicenter, double-blind trial in which patients with type 2 diabetes mellitus who were recently hospitalized for worsening heart failure were randomly assigned to receive sotagliflozin or placebo. The primary end point was the total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure (first and subsequent events). The trial ended early because of loss of funding from the sponsor.
Results:
A total of 1222 patients underwent randomization (608 to the sotagliflozin group and 614 to the placebo group) and were followed for a median of 9.0 months; the first dose of sotagliflozin or placebo was administered before discharge in 48.8% and a median of 2 days after discharge in 51.2%. Among these patients, 600 primary end-point events occurred (245 in the sotagliflozin group and 355 in the placebo group). The rate (the number of events per 100 patient-years) of primary end-point events was lower in the sotagliflozin group than in the placebo group (51.0 vs. 76.3; hazard ratio, 0.67; 95% confidence interval [CI], 0.52 to 0.85; P<0.001). The rate of death from cardiovascular causes was 10.6 in the sotagliflozin group and 12.5 in the placebo group (hazard ratio, 0.84; 95% CI, 0.58 to 1.22); the rate of death from any cause was 13.5 in the sotagliflozin group and 16.3 in the placebo group (hazard ratio, 0.82; 95% CI, 0.59 to 1.14). Diarrhea was more common with sotagliflozin than with placebo (6.1% vs. 3.4%), as was severe hypoglycemia (1.5% vs. 0.3%). The percentage of patients with hypotension was similar in the sotagliflozin group and the placebo group (6.0% and 4.6%, respectively), as was the percentage with acute kidney injury (4.1% and 4.4%, respectively). The benefits of sotagliflozin were consistent in the prespecified subgroups of patients stratified according to the timing of the first dose.
Conclusions:
In patients with diabetes and recent worsening heart failure, sotagliflozin therapy, initiated before or shortly after discharge, resulted in a significantly lower total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure than placebo. (Funded by Sanofi and Lexicon Pharmaceuticals; SOLOIST-WHF ClinicalTrials.gov number, NCT03521934.).
Insights
Sodium-glucose cotransporter 2 (SGLT2) inhibitors like sotagliflozin significantly reduced heart failure events in patients recently hospitalized for worsening heart failure. This study demonstrates the safety and efficacy of initiating SGLT2 inhibitors shortly after hospital discharge.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors are known to reduce heart failure hospitalizations in stable patients.
- The safety and efficacy of initiating SGLT2 inhibitors immediately after decompensated heart failure remain undetermined.
Purpose of the Study:
- To evaluate the safety and efficacy of sotagliflozin in patients with type 2 diabetes mellitus recently hospitalized for worsening heart failure.
- To assess the impact of early sotagliflozin initiation on cardiovascular death and heart failure-related events.
Main Methods:
- A multicenter, double-blind trial randomized 1222 patients with type 2 diabetes and recent heart failure hospitalization to receive sotagliflozin or placebo.
- The primary endpoint included total cardiovascular deaths, hospitalizations, and urgent visits for heart failure.
- Sotagliflozin or placebo was administered either before discharge or within days after discharge.
Main Results:
- Sotagliflozin significantly reduced the primary endpoint events compared to placebo (hazard ratio, 0.67; P<0.001).
- Rates of cardiovascular death and all-cause mortality were numerically lower in the sotagliflozin group.
- Adverse events like diarrhea and severe hypoglycemia were more frequent with sotagliflozin; hypotension and acute kidney injury rates were similar.
Conclusions:
- Initiating sotagliflozin therapy before or shortly after hospital discharge significantly reduced cardiovascular death and heart failure events in patients with diabetes and recent worsening heart failure.
- The findings support the early use of SGLT2 inhibitors in this high-risk patient population.
Related Concept Videos
01:30Heart Failure V: Medical Management
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:22Heart Failure Drugs: Diuretics
01:22Heart Failure Drugs: β-Blockers
01:26Heart Failure Drugs: Inotropic Agents
01:22Heart Failure VI: Adjunct Therapies