But it was significantly reduced, and I think its a real finding. This content is available for meeting attendees and/or Platinum Members.

To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. Eligible patients were randomized in a 1:1 fashion to either sotagliflozin 400 mg daily (n = 5,292) or placebo (n = 5,292). Sotagliflozin in patients with diabetes and chronic kidney disease. The second goal was to see if it was. The primary endpoint is the total occurrences (first and potentially subsequent) of CV death, Hospitalization for Heart Failure (HHF), and urgent HF visits after randomization. If it shows a reduction in MACE, then Id have to say this is a class effect for SGLT-2 inhibitors as well, and what we saw in SCORED in terms of MACE reduction wasnt the SGLT-1 but rather that we studied a population that was just the right combination, Bhatt said. Like Bhatt and Santos-Gallego, Wilcox said these benefits need to be confirmed in future trials. Verma noted that trials testing two SGLT2 inhibitors in patients with HFpEF, dapagliflozin in, With SCORED, which also lost funding that led to curtailed follow-up, investigators focused on patients with diabetes and chronic kidney disease, with and without albuminuria, and at least one major cardiovascular risk factor.

This is the first agent to show this benefit; trials with other agents such as EMPEROR-Preserved with empagliflozin are ongoing. Congenital Heart Disease and Pediatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Pulmonary Hypertension and Venous Thromboembolism, ACC Anywhere The ACC.22 Meeting on Demand Program, CardioSource Plus for Institutions and Practices, Annual Scientific Session and Related Events, ACC Quality Improvement for Institutions Program, National Cardiovascular Data Registry (NCDR), Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation, Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease, Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure, Heart Failure and Cardiomyopathies Clinical Topic Collection, Intravascular LVAD vs. IABP in AMI With Shock, Association of Mediterranean Diet With Cognitive Decline, Atrial Fibrillation Presentation and Early Rhythm Control Outcomes, The Outcomes Registry For Cardiac Conditions in Athletes (ORCCA) Study: Large-Scale Data Capture For the Sports Cardiology and Sports Medicine Communities, Congenital Heart Disease and Pediatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Pulmonary Hypertension and Venous Thromboembolism, Estimated glomerular filtration rate (eGFR) between 25-60 ml/min/1.73 m, CV risk factors (at least 1 major if age >18 years, at least 2 minor if age 55 years), Planned use of sodium-glucose cotransporter-2 (SGLT2) inhibitor, Left ventricular ejection fraction (LVEF): 60%, Urinary albumin-to-creatinine ratio: 75 mg/g, Use of any renin-angiotensin-aldosterone system inhibitor: 88%, First occurrence of CV death or HF hospitalization: 8.3% vs. 9.5% (HR 0.77, 95% CI 0.66-0.91, p = 0.001), First sustained 50% decrease in eGFR, chronic dialysis, renal transplant, or sustained eGFR <15: 0.5% vs. 0.7% (p = 0.11), Volume depletion: 5.3% vs. 4.0% (p = 0.003), Genital fungal infections: 2.4% vs. 0.9% (p < 0.0001), EF 40 to <50%: 45.2% vs. 71.3% (p = 0.02), No history of HF, EF 50%: 5.2% vs. 6.2% (p = 0.04). Treatment with sotagliflozin also cut total nonfatal strokes by 31% relative to placebo in patients with a history of CVD, and by a relative 38% in those without a CVD history. An additional analysis reported by Dr. Bhatt used combined data from SCORED as well as several additional randomized trials of sotagliflozin involving a total of more than 20,000 patients that showed a significant 21% reduction in the incidence of MACE compared with placebo. All rights reserved. Receive the the latest news, research, and presentations from major meetings right to your inbox. For the majority of patients in HF admitted to hospital and who have responded well to diuretics, I would be comfortable prescribing the SGLT2 inhibitors, said Santos-Gallego. As a class, these agents will likely play a prominent role among patients with CKD and HF, and possibly even in the absence of T2DM. Please remove one or more studies before adding more. It really shows us that the earlier, the better, he said, when it comes to initiating treatment for patients following acute HF. 2022 MJH Life Sciences and HCPLive - Clinical news for connected physicians. He also highlighted the timeliness and durability of the novel dual-pathway-targeting agent in treated SCORED patients. The SCORED and SOLOIST-WHF trials, both presented this week at the virtual American Heart Association 2020 Scientific Sessions and published simultaneously in the New England Journal of Medicine, showed that sotagliflozin reduced the risk of hospitalizations for heart failure (HF) in diabetic patients with chronic kidney disease (CKD) and decompensated HF, respectively, and this benefit was largely evident after just a few months. CV death was not reduced in the pooled intention-to-treat analysis, but a reduction was noted in the on-treatment analysis (HR 0.77, 95% CI 0.60-0.98). including both MI and stroke. He completed his undergraduate degrees at Queens. Two new studies provide a boost to the use of sotagliflozin (Zynquista; Sanofi Aventis/Lexicon) in two very distinct patient populations, adding more data to the evolving sodium-glucose cotransporter 2 (SGLT2) inhibitor story. There are important nuances to the coming trials, he said, noting that EMPEROR-Preserved will include patients with chronic HF, a different population than the acute HF patient in SOLOIST-WHF. All material on this website is protected by copyright, Copyright 1994-2022 by WebMD LLC. Finally, given its dual action on SGLT1 and SGLT2, sotagliflozin significantly reduced HbA1c levels in SCORED patients with estimated glomerular filtrations rates (eGFR) < 30 mL/min/1.73 m2 and those with less impairment. Patients were stabilized in hospital before randomization to treatment with sotagliflozin or placebo, with criteria for stability including no need for oxygen, systolic blood pressure of 100 mm Hg or greater, no need for intravenous inotropic or vasodilator therapy, and transitioning from IV to oral diuretic therapy. The two original coprimary endpoints were a classic MACE endpoint (death from cardiovascular causes, nonfatal MI, or nonfatal stroke), designed to assess the safety of the diabetes drug, as well the composite of cardiovascular death and hospitalizations for HF, Finally, given its dual action on SGLT1 and SGLT2, sotagliflozin significantly reduced HbA1c levels in SCORED patients with estimated glomerular filtrations, Sotagliflozin in patients with diabetes and recent worsening heart failure, Sotagliflozin in patients with diabetes and chronic kidney disease. Bhatt said SCORED is the first trial to demonstrate a reduction in stroke with an SGLT2 inhibitor, noting there was some initial controversy surrounding higher stroke numbers with empagliflozina finding later deemed to be a spurious findingin, Fewer MACE in Diabetic Patients Taking SGLT2 Inhibitors vs DPP-4 Inhibitors, EMPEROR-Reduced: Empagliflozin Cuts Hospitalizations, CV Mortality in HFrEF, efficacious as no trial had really done this before in an adequately powered study, he added. Right now, there are a lot of data supporting use of SGLT2 inhibitors in stable HFeither treating patients who already have it or preventing itbut SOLOIST-WHF is the next evolution, said Bhatt. 2019 Feb 28;18(1):20. doi: 10.1186/s12933-019-0828-y. With SCORED, which also lost funding that led to curtailed follow-up, investigators focused on patients with diabetes and chronic kidney disease, with and without albuminuria, and at least one major cardiovascular risk factor. Join our newsletter! Michaels Hospital, Canada), another of the SOLOIST-WHF investigators, said the trial provides data for use of SGLT2 inhibitors in a patient population where none previously existed. Cefalo CMA, Cinti F, Moffa S, Impronta F, Sorice GP, Mezza T, Pontecorvi A, Giaccari A. Sotagliflozin, the first dual SGLT inhibitor: current outlook and perspectives.

Presented by Dr. Deepak Bhatt at the American Heart Association Virtual Scientific Sessions, November 16, 2020. Lexicon Pharmaceuticals, the company developing sotagliflozin, has announced plans to resubmit its new drug application for sotagliflozin to the FDA later in 2022, with the agency's approval decision likely occurring late in 2022 or sometime during 2023. "The results suggest a benefit [from sotagliflozin] on atherosclerotic events, which could be a potential advantage" compared with the SGLT2 inhibitors, "but the heterogeneity of this effect" among these agents means that more confirmatory data are needed for sotagliflozin, Dr. O'Donoghue said in an interview. Presented by Dr. Deepak L. Bhatt at the American College of Cardiology Annual Scientific Session (ACC 2022), Washington, DC, April 2, 2022. It is not approved for the treatment of type 2 diabetes. Copyright 2022. "This stroke benefit has not been clearly seen" with any agent from the closely related sodium-glucose cotransport-2 (SGLT2) inhibitor class, and "the MACE benefit appeared very early," within 3 months from the start of sotagliflozin treatment, "which may be because of the SGLT1 inhibition," Dr. Bhatt said during his report.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03315143. Sotagliflozin in patients with diabetes and recent worsening heart failure. "There is a lot of enthusiasm for the concept" of combined inhibition of the SGLT1 and 2 receptors, and if more evidence for unique benefits of this effect accumulate "it may lead to increased enthusiasm for sotagliflozin," she said. The study, "Effect of Sotagliflozin on CV and Renal Events in Patients with CV Risk, T2DM, and Renal Impairment," was presented at ACC 2022. To comment please, Comments on Medscape are moderated and should be professional in tone and on topic.

In an interview with HCPLive during ACC 2022, Bhatt detailed the unique characteristics of SGLT-2 and SGLT-1 inhibition: the former is expressed in the kidney, while the latter is expressed in both the kidney and the gutmeaning gut inhibition can lead to slowed glucose absorption. Please use this form to submit your questions or comments on how to make this article more useful to clinicians. You have reached the maximum number of saved studies (100). The SOLOIST-WHF study included patients with diabetes aged 18 to 85 years hospitalized for heart failure and receiving IV diuretic therapy. You must declare any conflicts of interest related to your comments and responses. Subodh Verma. This early anti-ischemic benefit of sotagliflozin needs to be explored further, he added. Total occurrences of HHF and urgent HF visits after randomization, Time to occurrence of CV Death after randomization, Total occurrences of CV death, HHF, non-fatal stroke, and non-fatal myocardial infarction after randomization, Total occurrences of CV Death, HHF, urgent HF Visits, and HF while hospitalized after randomization, Time to first occurrence after randomization of the composite of sustained 50% decrease in eGFR from baseline (for 30 days), chronic dialysis, renal transplant, or sustained eGFR<15 mL/min/1.73m2 (for 30 days) in the total patient population, Occurrence of all-cause mortality after randomization, Total occurrences of CV death, non-fatal stroke, and non-fatal myocardial infarction after randomization. Do not delay the initiation of any of the four pillars of [HF] therapy. The treatment benefit in those with heart failure with preserved ejection fraction (HFpEF) is the first time a treatment effect with an SGLT2 inhibitor has been demonstrated in this patient population, said Bhatt. Patients who present with acute decompensated heart failure undergo diuresis, and kidney function is likely to fluctuate because of the diuretics and other medications. There was no difference in cardiovascular mortality. All rights reserved. Part of these overall MACE benefits resulted from similar improvements from sotagliflozin treatment on the individual outcomes of total nonfatal MI and total nonfatal strokes. Burnout Might Really Be Depression; How Do Doctors Cope? Carlos Santos-Gallego. Sotagliflozin in Patients With Diabetes and Chronic Kidney Disease. For the majority of patients in HF admitted to hospital and who have responded well to diuretics, I would be comfortable prescribing the SGLT2 inhibitors, said Santos-Gallego. Epub 2020 Nov 16. "A lot will also depend on pricing decisions" for sotagliflozin, if it receives U.S. marketing approval from the Food and Drug Administration.

Treatment with sotagliflozin cut these MIs by a significant 31% in patients with a history of CVD relative to patients who received placebo, and by a relative 34% in those without a CVD event in their history, a difference compared with placebo that fell short of significance, said Dr. Bhatt, professor of medicine at Harvard Medical School and executive director of interventional cardiovascular programs at Brigham and Women's Health, both in Boston. That treatment benefit occurred early, within a month of randomization, and was evident in those with preserved and reduced ejection fractions. It says: use it upstream. For Verma, even though the trial had to prematurely halt enrollmentand Sanofi severed their partnership with Lexicon last year, placing the drugs future in limbothe result demonstrates how powerful the SGLT2 inhibitors are in the context of HF. Do not delay the initiation of any of the four pillars of [HF] therapy.. Do not delay the initiation of any of the four pillars of [HF] therapy. Deepak Bhatt. After a median follow-up of 16 months, there were 5.6 and 7.5 primary endpoint events per 100 patient-years in the sotagliflozin- and placebo-treated patients, respectively (HR 0.74; 95% CI 0.63-0.88).

American College of Cardiology (ACC) 2022 Scientific Sessions. Patients who present with acute decompensated heart failure undergo diuresis, and kidney function is likely to fluctuate because of the diuretics and other medications. Talk with your doctor and family members or friends about deciding to join a study. The results of this trial are similar to those noted with canagliflozin in the CREDENCE trial and with empagliflozin in the EMPA-REG OUTCOME trial. The goal of the trial was to assess the safety and efficacy of sotagliflozin in reducing cardiovascular (CV) events among patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Patrick Flume, MD: Could a Persistent Cough be Bronchiectasis? Information provided by (Responsible Party): Study duration per participant is approximately 27 to 51 months, assuming approximately 24 months of recruitment, and approximately 27 months of follow-up after the last patient is randomized.

During histalk, Dr. Bhatt said that sotagliflozin was potentially superior to the agents that inhibit only SGLT2. Study record managers: refer to the Data Element Definitions if submitting registration or results information. Individual Participant Data (IPD) Sharing Statement: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial. For more information, visit http://www.crf.org. Presented by Dr. Deepak L. Bhatt at the American College of Cardiology Virtual Annual Scientific Session (ACC 2021), May 17, 2021. The first question was whether this was really a safe thing to do. Studies a U.S. FDA-regulated Drug Product: Studies a U.S. FDA-regulated Device Product: Product Manufactured in and Exported from the U.S.: Total occurrences of HHF and urgent visit for HF, Total occurrences of cardiovascular death, HHF, urgent HF visit, non-fatal stroke, and non-fatal myocardial infarction, Total occurrences of cardiovascular death, HHF, urgent HF visit, and HF while hospitalized, First occurrence of a sustained 50% decrease in estimated glomerular filtration rate (eGFR) from baseline (for 30 days), chronic dialysis, renal transplant or sustained eGFR <15 mL/min/1.73m2 (for 30 days), Total occurrences of cardiovascular death, non-fatal stroke, and non-fatal myocardial infarction, Total occurrences of CV Death and Heart Failure Events [TimeFrame:Baseline through a maximum of 33 months], Total occurrences of Heart Failure Events [TimeFrame:Baseline through a maximum of 33 months], CV Death [TimeFrame:Baseline through a maximum of 33 months], Total occurrences of 3-Point MACE plus HHF events [TimeFrame:Baseline through a maximum of 33 months], Total occurrences of CV Death, HF Events, and HF while hospitalized [TimeFrame:Baseline through a maximum of 33 months], Time to composite renal event [TimeFrame:Baseline through a maximum of 33 months], All-Cause Mortality [TimeFrame:Baseline through a maximum of 33 months], Total occurrences of 3-Point MACE [TimeFrame:Baseline through a maximum of 33 months].