FDA Approves Sotagliflozin to Treat Heart Failure

Credit: Food and Drug Administration

The U.S. Food and Drug Administration has approved sotagliflozin (Inpefa) for the treatment of heart failure across the full spectrum of left ventricular ejection fraction.

The approval, announced by Lexicon Pharmaceuticals on May 26, 2023, is the first approval of an SGLT1/2 inhibitor in government agency history, reducing the risk of cardiovascular death, heart failure hospitalization, and heart failure emergency hospital visits. It has been shown to be a reducing agent. Adults with heart failure or type 2 diabetes, chronic kidney disease, and other cardiovascular risk factors.1

“The approval and breadth of indications for INPEFA are major milestones in Lexicon’s journey to fulfill its mission of pioneering medicines that transform patients’ lives,” said Lexicon CEO Ronnell Coates.1 “This important innovation is expected to be commercially available in the US market by the end of June 2023.”

The road to sotagliflozin’s historic approval was not an easy one. The drug was once marketed as a treatment for type 1 diabetes and was the subject of a four-year collaboration between Sanofi and Lexicon Pharmaceuticals, following the acquisition of CRL for type 1 diabetes in July 2019. has ended.2, 3

With its approval on May 26, 2023, sotagliflozin will become the first SGLT1/2 inhibitor to obtain such, boasting SGLT2 inhibition as a mechanism of action with heart failure indications across the ejection fraction spectrum3 It joins dapagliflozin and empagliflozin as the second agent. An NDA for sotagliflozin as a treatment for heart failure, submitted by Lexicon Pharmaceuticals in July 2022, was supported by data from the SOLOIST-WHF and SCORED trials.Four

The Phase 3, double-blind, randomized, placebo-controlled trial SOLOIST-WHF enrolled and randomized a cohort of 1,222 people with type 2 diabetes recently hospitalized with worsening heart failure. The trial’s primary endpoint was combined total cardiovascular mortality and worsening of heart failure events.Five

Although stopped early due to lack of funding due to the COVID-19 pandemic, study results show that patients who received sotagliflozin received placebo therapy during a median follow-up of 9.0 months A significant reduction in primary endpoint event rates compared with patients was demonstrated. (51.0 vs 76.3 events per 100 patient-years; hazard ratio [HR]0.67 [95% confidence interval [CI]0.52-0.85]; P. < .001). Further analysis data from the trial showed that sotagliflozin was associated with a reduced risk of cardiovascular mortality (HR, 0.84) [95% CI, 0.58-1.22]) and all-cause mortality compared with placebo therapy. A post-hoc analysis of the trial provided results suggesting that treatment effects for the primary composite endpoint had achieved significance by 28 days of follow-up.Five

The SCORED trial was also a phase 3, double-blind, randomized, placebo-controlled trial, but unlike SOLOIST-WHF, it enrolled patient populations at risk for type 2 diabetes, chronic kidney disease, and cardiovascular disease. . As a result of early termination due to loss of funding, the study’s primary endpoint changed from first occurrence of a major adverse cardiovascular event (MACE) to a composite endpoint of worsening cardiovascular death or heart failure events was done. Of note, MACE endpoints included cardiovascular death, myocardial infarction, and stroke.6

The trial enrolled 10,584 patients and the cohort was followed for a median of 16 months. The study showed that patients receiving sotagliflozin had significantly reduced event rates for the primary endpoint compared with those receiving placebo (5.6 vs. 7.5 events per 100 patient-years). HR, 0.74) [95% CI, 0.63-0.88]; P. = .0004). When evaluating the first occurrence of MACE, the results showed . A post-hoc analysis of this trial suggested that treatment effects on cardiovascular death and worsening heart failure endpoints reached significance by 95 days of follow-up.6

In SOLOIST-WHF, a higher rate of adverse events with sotagliflozin use compared with placebo was diarrhea (6.9% vs 4.1%; P. = .032), genital fungal infection (0.8% vs 0.2%; P. = .12), corresponding to hypoglycemia (1.5% vs 0.3%; P. = .037). In SCORED, diarrhea (8.5% vs. 6.0%; P. < .0001), genital fungal infection (5.3% vs 4.0%; P. = .003), and volume reduction (2.4% vs 0.9%; P. < .0001) were more common with sotagliflozin than with placebo.5,6

“Based on the results observed in the SOLOIST-WHF study, initiating treatment with INPEFA before or at discharge may reduce the readmission burden on patients, caregivers, providers and the healthcare system. Yes,” said Craig Granowitz, M.D. , Senior Vice President and Chief Medical Officer of Lexicon.1 “Today’s FDA approval makes INPEFA a valuable option for physicians to consider as they look to treat patients transferring from hospital and to break the cycle of repeated hospitalizations.”


  1. Lexicon Pharmaceuticals, Inc. Lexicon has announced FDA approval of INPEFATM (sotagliflozin) for the treatment of heart failure. Lexicon Pharmaceuticals, Inc. May 26, 2023. Accessed May 26, 2023. https://www.lexpharma.com/media-center/news/2023-05-26-lexicon-announces-fda-approval-of-inpefa-Sotagliflozin for the treatment of heart failure.
  2. FDA will issue a full response to Zynquista(TM) (sotagliflozin). Sanofi. March 22, 2019. Accessed May 26, 2023. https://www.sanofi.com/en/media-room/press-releases/2019/2019-03-22-18-15-00-1759502.
  3. Lexicon Pharmaceuticals, Inc. Lexicon Pharmaceuticals has announced the termination of its collaboration and settlement with Sanofi. Lexicon Pharmaceuticals, Inc., September 10, 2019. Accessed May 26, 2023. https://www.globenewswire.com/news-release/2019/09/10/1913802/0/en/Lexicon-Pharmaceuticals-Announces-Termination-Alliance and Settlement with Sanofi.html.
  4. Lexicon Pharmaceuticals, Inc. Lexicon announced that the FDA has accepted a new drug application for sotagliflozin for the treatment of heart failure. Lexicon Pharmaceuticals, Inc., July 27, 2019. Accessed May 26, 2023. https://www.globenewswire.com/news-release/2022/07/27/2486783/0/en/Lexicon-Announces-FDA-Acceptance-New Drug Application for Sotagliflozin for the Treatment of Heart Failure.html.
  5. Effect of sotagliflozin on cardiovascular events in type 2 diabetic patients after exacerbation of heart failure. American College of Cardiology. November 16, 2020. Accessed May 26, 2023. https://www.acc.org/latest-in-Cardiology/Clinical-Trials/2020/11/11/22/00/SOLOIST-WHF.
  6. Effects of sotagliflozin on cardiovascular and renal events in patients with cardiovascular risk type 2 diabetes and moderate renal impairment. American College of Cardiology. November 16, 2020. Accessed May 26, 2023. https://www.acc.org/latest-in-Cardiology/Clinical-Trials/2020/11/11/22/02/SCORED.

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