Dual SGLT Inhibitors to Treat Heart Failure Materials

USING DUAL SGLT INHIBITORS TO TREAT HEART FAILURE

STEVEN MALEN, PharmD, MBA

Dr. Steven Malen graduated with a dual degree: Doctor of Pharmacy (PharmD) and Master of Business Administration (MBA) from the University of Rhode Island. Over his career, he has worked as a clinical pharmacist in the retail, specialty, and compounding sectors. He specialized and taught on topics from vaccines to veterinary compounding. Dr. Malen has also written a science fiction novel and taught and co- founded the concept of Patient Empowered Blockchain (P.E.B.). Currently, Dr. Malen continues to write, teach, and consult various companies in the healthcare sector.

Topic Overview

Recent breakthroughs in managing heart failure have introduced a promising class of medications known as Dual Sodium-Glucose Cotransporter Inhibitors (SGLT1 and SGLT2 inhibitors). These medications, initially designed for diabetes management, have demonstrated efficacy in reducing the risk of cardiovascular events and hospitalizations in heart failure patients. The intersection of cardiology and pharmacy practice is now more critical than ever, as pharmacists are uniquely positioned to contribute significantly to the optimal utilization of these therapies. The pharmacist, supported by pharmacy staff, has a role in patient education and care coordination in heart failure management.

Accreditation Statement

RxCe.com LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.

Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is 

Pharmacist  0669-0000-23-180-H01-P

Pharmacy Technician  0669-0000-23-181-H01-T

Credits: 1 hour of continuing education credit

Type of Activity: Knowledge

Media: Internet/Home study Fee Information: $4.99

Estimated time to complete activity: 1 hour, including Course Test and course evaluation

Release Date: October 27, 2023 Expiration Date: October 27, 2026

Target Audience: This educational activity is for pharmacists.

How to Earn Credit: From October 27, 2023, through October 27, 2026, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “educational activity;” and

Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

Credit for this course will be uploaded to CPE Monitor®.

Learning Objectives: Upon completion of this educational activity, participants should be able to:

Summarize the potential effectiveness of using dual SGLT inhibitors in heart failure management

Review the mechanism of action of sotagliflozin

Describe the warnings and precautions for the use of sotagliflozin

Recognize adverse events associated with the use of dual SGLT inhibitors

Disclosures

The following individuals were involved in developing this activity: Steven Malen, PharmD, MBA, and Pamela Sardo, PharmD, BS. Pamela Sardo was an employee of Rhythm Pharmaceuticals until March 2022 and has no conflicts of interest or relationships regarding the subject matter discussed. There are no financial relationships relevant to this activity to report or disclose by any of the individuals involved in the development of this activity.

© RxCe.com LLC 2023: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.

Introduction

Heart failure, a complex and prevalent cardiovascular condition, presents challenges and opportunities for healthcare providers. Dual SGLT inhibitors provide a newer option for heart failure management. This course discusses the mechanisms of action, clinical evidence, and patient selection criteria applicable to the use of dual SGLT inhibitors. The pharmacist, supported by pharmacy staff, has a role in patient education and care coordination in heart failure management.

Dual Sodium-Glucose Cotransporter Inhibitors

Recent breakthroughs in managing heart failure (HF) have introduced a promising class of medications known as Dual Sodium-Glucose Cotransporter Inhibitors (SGLT1 and SGLT2 inhibitors).1 These medications, initially designed for diabetes management, have demonstrated efficacy in reducing the risk of cardiovascular events and hospitalizations in HF patients.1 The intersection of cardiology and pharmacy practice is now more critical than ever, as pharmacists are uniquely positioned to contribute significantly to the optimal utilization of these therapies.1,2

Prevalence and Risk Factors for Heart Failure

Heart failure represents a significant global health concern with an alarming prevalence. In the United States alone, the prevalence of HF has surged beyond 5.8 million individuals, while worldwide, this staggering number surpasses 23 million, and these figures continue to rise.3 Equally concerning is the lifetime risk of HF development, which stands at one in five individuals. While some promising evidence suggests that the age-adjusted incidence of HF may have stabilized, the condition remains a substantial source of morbidity and mortality.4 Notably, the 5-year mortality rates associated with HF rival those of several malignancies.4 Furthermore, HF takes a considerable toll on healthcare systems, with an annual cost exceeding $39

billion in the United States, marked by frequent hospitalizations, readmissions, and outpatient visits.3,5

It is important to recognize that HF is a heterogeneous syndrome, its characteristics varying with factors such as age, gender, race or ethnicity, left ventricular ejection fraction (LVEF) status, and etiology, reflecting the need for tailored approaches to its management.6 These variations are also beginning to be better understood through epidemiological studies, shedding light on the pathophysiological differences between HF patients with reduced LVEF and those with preserved LVEF.6,7 Although HF usually involves the left ventricle, the right ventricle can play an important role as well, and right ventricle dysfunction should not be ignored.6,7

Multiple risk factors contribute to the incidence and severity of HF, providing insights into its complex etiology. Conditions like ischemic heart disease, hypertension, smoking, obesity, and diabetes, among others, have emerged as significant predictors of HF development.8 Understanding these risk factors not only aids in estimating HF incidence but also helps gauge its potential severity.

Dual SGLT Inhibitors

On May 26, 2023, the FDA granted approval for sotagliflozin (Inpefa®),9 a once-daily oral tablet designed to reduce the risk of cardiovascular death, hospitalization for HF, and urgent HF visits in adults with HF or type 2 diabetes mellitus.10 This approval also extends to individuals with HF and chronic kidney disease or other cardiovascular risk factors.10

The American Heart Association (AHA), the American College of Cardiology (ACC), and the Heart Failure Society of America (HFSA) have included the use of SGLT inhibitors as a treatment for HF in their 2022 joint guidelines.11 Additionally, the ACC's expert consensus statement in April 2023 emphasized the value of SGLT inhibitors as part of Guideline-Directed Medical

Therapy for patients with HF with preserved ejection fraction (HFpEF), suggesting their initiation in stable individuals without contraindications.12

Sotagliflozin’s Clinical Trials

Two clinical trials called the SOLOIST study and SCORED were used to evaluate sotagliflozin for treating heart failure patients.10,13 The SOLOIST study focused more on efficacy, while the SCORED trial reviewed the effectiveness and safety of sotagliflozin.

The SOLOIST study, a randomized, double-blind, placebo-controlled trial, focused on patients with type 2 diabetes mellitus admitted to healthcare facilities due to worsening HF.10 These patients were considered clinically stable based on specific criteria. The study included 1,222 patients, with 608 receiving sotagliflozin and 614 receiving a placebo. Treatment initiation occurred either in the hospital or shortly after discharge. The dose of sotagliflozin was up-titrated from 200 mg to 400 mg, with 56% of patients reaching the maximum dose within a median time of 16 days.10 Baseline characteristics revealed a predominantly older population with various comorbidities, including diabetes and heart-related medications. Sotagliflozin demonstrated superiority over placebo in reducing the risk of the primary composite endpoint, highlighting its potential clinical benefits.10 Table 1 below reviews SOLOIST clinical data.

The goal of the second clinical trial discussed here, called SCORED, was used to assess the safety and efficacy of sotagliflozin in reducing cardiovascular (CV) events among patients with type 2 diabetes mellitus and chronic kidney disease (CKD).10,13 After the trial stopped due to COVID, the primary endpoint was changed to CV death, HF hospitalization, and urgent visit for HF for sotagliflozin versus placebo, which reached significance (11.3% vs. 14.4%) by day 95 of follow-up. The benefit was a reduction of HF events, but there was also a reduction in CV death, myocardial infarction, and stroke.10,13

Table 1: SOLOIST Study: Primary Endpoint and Primary Endpoint Components10

^Based on investigator-reported events in all randomized patients

*Predefined primary endpoint

Sotagliflozin’s Mechanism of Action

Sotagliflozin acts as an inhibitor for SGLT2 and SGLT1.10 Inhibiting SGLT2 leads to reduced renal reabsorption of glucose and sodium, potentially impacting heart function by lowering pre-and afterload and reducing sympathetic activity.10 Simultaneously, inhibiting SGLT1 decreases intestinal glucose and sodium absorption, which may contribute to diarrhea as a side effect. However, the exact mechanism responsible for sotagliflozin's cardiovascular benefits remains to be established.10

Indications for Sotagliflozin

Sotagliflozin is an SGLT2 inhibitor designed to lower the risk of cardiovascular death, hospitalization due to HF, and urgent HF visits in two distinct groups: adults diagnosed with HF and those with HF and type 2

diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors.10

Dosing for Sotagliflozin

The recommended initial dosage for sotagliflozin is 200 mg taken orally once daily, preferably within an hour before the first meal of the day.10 After a minimum of two weeks, the dose can be increased to 400 mg once daily, depending on the patient's tolerance.10 If necessary, the dose can be reduced back to 200 mg. Tablets should be swallowed whole and should not be cut, crushed, or chewed. In case a dose is missed by more than 6 hours, the next dose should be taken as prescribed on the following day.10

Sotagliflozin’s Side Effects or Adverse Events

Common adverse reactions are mentioned in the table below. Additional side effects of sotagliflozin include the risk of diabetic ketoacidosis in patients with type 1 diabetes mellitus.10 Sotagliflozin may cause volume depletion and hypoglycemia when used concurrently with insulin and insulin secretagogues.10 Another side effect includes urosepsis which is a life- threatening complication of urinary tract infections (UTIs) that can spread to the bloodstream and cause septic shock. Sotagliflozin can also cause

pyelonephritis, which is an inflammation of the kidney and pelvis caused by bacterial infection.10

Finally, sotagliflozin may cause necrotizing fasciitis of the perineum (Fournier's Gangrene) or flesh-eating disease that affects your scrotum, penis, or perineum and, similarly, genital mycotic infections.10 The discontinuation rates due to adverse events in these trials were relatively low, with slight differences between the sotagliflozin and placebo groups.10 Table 2 reviews adverse reactions seen in 2 trials. The adverse reactions included in Table 2 are the ones seen in ≥2% of patients treated with sotagliflozin and which were greater than in the placebo group.

Table 2: Adverse Reactions from Sotagliflozin Compared to Placebo10

*Adverse reactions from 2 trials are included here if seen in ≥2% of patients treated with sotagliflozin, and if greater than the adverse reactions seen in the placebo group

Drug-Drug Interactions

Sotagliflozin may interact with other medications, such as digoxin, uridine 5'-diphospho-glucuronosyltransferase (UGT) inducers (such as rifampin), and lithium. Patients taking sotagliflozin with concomitant digoxin

should be monitored appropriately, as blood values of digoxin may increase.10 The coadministration of rifampicin, an inducer of UGTs, with a single dose of 400 mg sotagliflozin, resulted in a decrease in the exposure to sotagliflozin. This decrease in exposure to sotagliflozin may decrease efficacy.10

Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations. Monitor serum lithium concentrations frequently and adjust lithium dosage as needed.10

Handling and Storage of Sotagliflozin

Store sotagliflozin at room temperature between 68°F and 77°F (20°C and 25°C).10 Temperature excursions between 59°F and 86°F (15°C and 30°C) are permitted.10

Sotagliflozin and Special Populations Surgical Patients

Patients scheduled for major surgery or procedures that require fasting should stop taking sotagliflozin at least 3 days before the scheduled event. These patients may restart sotagliflozin when they are stable and able to eat again.10

Diabetic Ketoacidosis (DKA)

Sotagliflozin significantly increases the risk of DKA in patients with type 1 diabetes mellitus, even with normal blood sugar levels. This risk may be greater with higher doses of sotagliflozin.10 DKA is a life-threatening condition, and there have been postmarketing reports of fatal events in patients with type 2 diabetes using SGLT2 inhibitors.10

Other risk factors for DKA include type 2 diabetes mellitus, pancreatic disorders, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, insulin dose reduction, volume depletion, and alcohol abuse.10 Signs and symptoms of DKA include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath.10 If ketoacidosis is suspected, discontinue sotagliflozin and promptly evaluate and treat ketoacidosis if confirmed. Monitor patients for resolution of DKA before restarting sotagliflozin. All patients should be educated on the signs and symptoms of DKA and instructed to discontinue sotagliflozin and seek medical attention immediately if signs and symptoms occur.10

Volume Depletion

Sotagliflozin can cause volume depletion, which can lead to symptomatic hypotension and acute kidney injury.10 Patients at increased risk for volume depletion include those with impaired renal function, elderly patients, and patients on loop diuretics.10 Before initiating sotagliflozin in patients with one or more of these risk factors, assess volume status and renal function. Monitor for signs and symptoms of hypotension and renal function after initiating therapy.10

Pregnancy

Sotagliflozin is not recommended during the second and third trimesters of pregnancy because of animal data showing renal effects.10 There are risks to the mother and fetus associated with untreated HF in pregnancy, so women with HF should talk to their doctor about the risks and benefits of continuing or discontinuing sotagliflozin during pregnancy.10

Lactation

Sotagliflozin is not recommended for women who are breastfeeding because it is not known whether it passes into breast milk or if it could harm a breastfed baby.10 There is a potential risk to the developing human kidney.10

Pediatric

Sotagliflozin is not recommended in patients under 18 because safety and efficacy have not been tested.10

Geriatric

No sotagliflozin dosage change is recommended based on age, but elderly patients may be at increased risk for volume depletion adverse reactions, including hypotension.10 In patients ≥ 65 years of age, a higher proportion of patients treated with sotagliflozin had adverse reactions to volume depletion.10

Renal Impairment

Sotagliflozin was evaluated in patients with chronic kidney disease (CKD) with an estimated glomerular filtration rate (eGFR) of 25 to 60 mL/min/1.73 m2 and in patients with HF with an eGFR of less than 60 mL/min/1.73 m2.10 The safety profile of sotagliflozin in these patients was similar to the safety profile in patients with normal kidney function.10 However, patients with an eGFR of less than 30 mL/min/1.73 m2 may be at increased risk for volume-related adverse events, such as hypotension and dizziness.10 Efficacy and safety studies with sotagliflozin did not enroll patients with an eGFR of less than 25 mL/min/1.73 m2 or on dialysis.10 Patients who started sotagliflozin in these studies were discontinued if their eGFR fell below 15 mL/min/1.73 m2 or they were started on chronic dialysis.10

Hepatic Impairment

Exposure to sotagliflozin has been shown to be increased in patients with moderate and severe hepatic impairment.10 No dosage adjustment is necessary in patients with mild hepatic impairment, but sotagliflozin is not recommended in patients with moderate or severe hepatic impairment.10

Future Trends

Sotagliflozin research is ongoing. One clinical trial is investigating the safety and tolerability of renal transplant recipients (named START).14 The primary outcome measure is to determine the reversibility of eGFR changes.14

Another study is investigating sotagliflozin in HF with preserved ejection fraction (HFpEF).15 The primary outcome measure will explore changes in left ventricular mass in cardiac magnetic resonance imaging (CMRI).15

Sotagliflozin received FDA approval with a broad heart-failure indication; however, formal trial data in patients without diabetes is not available at this time.16 The status of future trials in participants without diabetes is unknown.

Patient Counseling

Pharmacy technicians and pharmacists have a key responsibility with patients taking sotagliflozin. Pharmacists may answer questions and counsel patients. Pharmacy technicians may direct them to read the Medication Guide. Sotagliflozin can cause potentially fatal ketoacidosis, especially in patients with type 1 diabetes mellitus.10 If individuals experience symptoms of ketoacidosis, such as nausea, vomiting, abdominal pain, tiredness, or labored breathing, they should stop taking sotagliflozin and seek medical attention immediately.10

Sotagliflozin can cause symptomatic hypotension, especially in patients who are dehydrated.10 Patients should be counseled to drink plenty of fluids while taking sotagliflozin.10 The pharmacy technician can also ensure an auxiliary label is placed on the container regarding drinking fluids.

Sotagliflozin can increase the risk of severe urinary tract infections.10 If patients experience symptoms of a urinary tract infection (UTI), such as fever, pain, or burning when urinating, they should seek medical attention promptly.10 If pharmacy technicians notice a purchase of over-the-counter

products for UTI symptoms in individuals prescribed sotagliflozin, they should notify the pharmacist.

If a patient takes sotagliflozin with insulin or insulin secretagogues, the risk of hypoglycemia may increase.10 The healthcare provider may need to adjust the insulin or insulin secretagogue dose to reduce the risk of hypoglycemia.

Necrotizing fasciitis of the perineum has occurred in patients with diabetes mellitus who took sotagliflozin.10 If pain, tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum occurs, along with a fever above 100.4°F or malaise, the individual should seek medical attention immediately.10

Genital mycotic infections in females (e.g., vulvovaginitis) and males (e.g., balanitis) may occur.10 Vaginal yeast infections and yeast infections of the penis may occur in patients taking sotagliflozin.10 If a patient experiences symptoms of a genital mycotic infection, such as itching or discharge, seek treatment from a healthcare provider.10 The pharmacy technician should inform the pharmacist if the patient taking sotagliflozin comes to the counter with over-the-counter treatments for yeast infections.

Hypersensitivity reactions, such as urticaria, anaphylactic reactions, and angioedema, have been reported with other SGLT2 inhibitors.10 If a rash, hives, swelling, or difficulty breathing occurs, the individual should stop taking sotagliflozin and seek medical attention immediately.10

Sotagliflozin is not recommended for use in pregnant women.10 If pregnant or planning to become pregnant, a healthcare provider should be consulted about the risks and benefits of taking sotagliflozin.10 Sotagliflozin is not recommended for use in breastfeeding women.10

Patients taking sotagliflozin will test positive for glucose in their urine due to its mechanism of action.10 If a dose of sotagliflozin is missed by more than 6 hours, take the next dose as prescribed the next day. Do not take two doses of sotagliflozin at the same time.10

Summary

The FDA approval of sotagliflozin for HF is a significant development. Sotagliflozin is the first SGLT inhibitor approved for HF in a wide range of patients with comorbidities such as chronic kidney disease and other cardiovascular risk factors. The SOLOIST study demonstrated the superiority of sotagliflozin over placebo in reducing the risk of HF hospitalization and death in patients with type 2 diabetes mellitus admitted to healthcare facilities due to worsening HF.

As a vital part of the healthcare team, pharmacists play a pivotal role in patient care, and their expertise is continuously sought to optimize treatment outcomes. Pharmacists can contribute to sotagliflozin medication use and management, as well as patient counseling, while pharmacy technicians may ensure dispensing functions, proper storage, and monitoring for drug interactions are completed.

Course Test

Which of the following is TRUE regarding the SCORED trial?

After the trial stopped due to COVID, the primary endpoint was changed to CV death, HF hospitalization, and urgent visit for HF for sotagliflozin versus placebo

The goal of the trial was to assess the safety and efficacy of sotagliflozin in reducing urinary tract infections among patients with type 1 diabetes mellitus

The trial started during COVID with a primary endpoint of reducing long COVID and assessing CV death

The goal of the trial was to assess outpatient visits, the need for respiratory therapy, and HF hospitalization

Which of the following statements is true regarding the FDA approval of sotagliflozin and its use in heart failure and type 2 diabetes mellitus?

Sotagliflozin is approved only for HF patients with preserved left ventricular ejection fraction

The American Heart Association (AHA) and the American College of Cardiology (ACC) have not included the use of SGLT inhibitors for HF treatment.

Sotagliflozin's approval extends to individuals with chronic kidney disease but not other cardiovascular risk factors.

Sotagliflozin is approved to reduce the risk of cardiovascular death and HF-related hospitalization in adults with HF or HF with type 2 diabetes mellitus

What was the primary finding of the SOLOIST study, a trial involving patients with type 2 diabetes mellitus admitted to healthcare facilities for worsening heart failure?

The study showed that sotagliflozin was ineffective in reducing the risk of heart failure exacerbation.

Sotagliflozin significantly reduced the risk of adverse events in patients with diabetes and heart failure.

Sotagliflozin demonstrated superiority over placebo in reducing the risk of the primary composite endpoint.

The study found that sotagliflozin was most effective when initiated long after hospital discharge.

Which of the following statements about sotagliflozin's mechanism of action is true?

Sotagliflozin primarily inhibits SGLT1, leading to reduced renal reabsorption of glucose and sodium.

Inhibiting SGLT2 reduces renal reabsorption of glucose and sodium, potentially impacting heart function by lowering pre-and afterload and reducing sympathetic activity.

Inhibiting SGLT2 and SGLT1 simultaneously has no impact on heart function.

Inhibiting SGLT1 increases sympathetic activity and contributes to sotagliflozin's cardiovascular benefits.

What potential interactions should healthcare providers be mindful of when prescribing sotagliflozin to patients?

Sotagliflozin increases the exposure to digoxin and rifampicin.

Concomitant use of sotagliflozin and lithium has no impact on serum lithium concentrations.

The coadministration of rifampicin with sotagliflozin increases sotagliflozin's efficacy.

Sotagliflozin may decrease serum lithium concentrations when used concomitantly with lithium.

What precautions should be taken with sotagliflozin before major surgery or fasting-related procedures?

Continue taking sotagliflozin without any changes.

Start taking sotagliflozin when fasting begins.

Stop taking sotagliflozin at least 3 days before major surgery.

Increase the dose of sotagliflozin before surgery.

What risk is associated with sotagliflozin in patients with type 1 diabetes mellitus?

Significantly increased risk of diabetic ketoacidosis

Increased risk of otitis media

Increased risk of hypertension

Greater efficacy in lowering blood sugar levels

Who is at an increased risk of volume depletion when taking sotagliflozin?

Patients with normal renal function

Patients with diabetes mellitus

Patients of any age

Patients with impaired renal function

What should occur when faced with symptoms of ketoacidosis while taking sotagliflozin?

Continue taking sotagliflozin and monitor your symptoms.

Stop taking sotagliflozin and seek medical attention immediately.

Reduce your fluid intake to prevent ketoacidosis.

Adjust your insulin dose to manage the symptoms.

What is a potential side effect related to urinary tract health when taking sotagliflozin?

Increased urinary frequency

Decreased risk of urinary tract infections

Increased risk of severe urinary tract infections.

Improved urinary function

References

Cefalo CMA, Cinti F, Moffa S, et al. Sotagliflozin, the first dual SGLT inhibitor: current outlook and perspectives. Cardiovasc Diabetol. 2019;18(1):20. Published 2019 Feb 28. doi:10.1186/s12933-019-0828-

y

Warden BA, Shapiro MD, Fazio S. The Role of the Clinical Pharmacist in a Preventive Cardiology Practice. Ann Pharmacother. 2019;53(12):1214-1219. doi:10.1177/1060028019864669

Bui AL, Horwich TB, Fonarow GC. Epidemiology and risk profile of heart failure. Nat Rev Cardiol. 2011;8(1):30-41. doi:10.1038/nrcardio.2010.165

Xu J, Murphy SL, Kochanek KD, Arias E. Mortality in the United States, 2021. NCHS Data Brief. 2022;(456):1-8.

Al-Tamimi MA, Gillani SW, Abd Alhakam ME, Sam KG. Factors Associated With Hospital Readmission of Heart Failure Patients. Front Pharmacol. 2021;12:732760. Published 2021 Oct 11. doi:10.3389/fphar.2021.732760

Pazos-López P, Peteiro-Vázquez J, Carcía-Campos A, García-Bueno L, de Torres JP, Castro-Beiras A. The causes, consequences, and treatment of left or right heart failure. Vasc Health Risk Manag. 2011;7:237-254. doi:10.2147/VHRM.S10669

Gabriele Fragasso. The Concept of "Heart Failure with Preserved Ejection Fraction": Time for a Critical Reappraisal. Rev. Cardiovasc. Med. 2023, 24(7), 202. doi.org/10.31083/j.rcm2407202

Crisafulli A, Pagliaro P, Roberto S, et al. Diabetic Cardiomyopathy and Ischemic Heart Disease: Prevention and Therapy by Exercise and Conditioning. Int J Mol Sci. 2020;21(8):2896. doi: 10.3390/ijms21082896

US Pharmacist. Once-Daily Inpefa Approved for Treating Heart Failure. US Pharm. July 17, 2023. https://www.uspharmacist.com/article/oncedaily-inpefa-approved-for- treating-heart- failure#:~:text=On%20May%2026%2C%202023%2C%20Lexicon,dise ase%2C%20and%20other%20cardiovascular%20risk. Accessed October 25, 2023.

Inpefa. Prescribing information. Lexicon Pharmaceuticals Inc. May 2023. https://www.lexpharma.com/inpefa-US-PI.pdf . Accessed October 1, 2023.

Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint

Committee on Clinical Practice Guidelines [published correction appears in Circulation. 2022 May 3;145(18):e1033] [published correction appears in Circulation. 2022 Sep 27;146(13):e185] [published correction appears in Circulation. 2023 Apr 4;147(14):e674].

Circulation. 2022;145(18):e895-e1032. doi:10.1161/CIR.0000000000001063

Kittleson MM, Panjrath GS, Amancherla K, et al. 2023 ACC Expert Consensus Decision Pathway on Management of Heart Failure With Preserved Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2023;81(18):1835-1878. doi:10.1016/j.jacc.2023.03.393

Bhatt DL, Szarek M, Pitt B, et al., on behalf of the SCORED Investigators. Sotagliflozin in Patients With Diabetes and Chronic Kidney Disease. N Engl J Med. 2021;384(2):129-39. doi: 10.1056/NEJMoa2030186

Sotagliflozin Safety and Tolerability Among Renal Transplant Recipients (START). Clinicaltrials.gov. January 31, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05405556?cond=sotagliflo zin&draw=2&rank=1. Accessed October 16, 2023.

Sotagliflozin in Heart Failure With Preserved Ejection Fraction (HFpEF) Patients. Clinicaltrials.gov. August 21, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05562063?cond=sotagliflo zin&draw=2&rank=3. Accessed October 16, 2023.

Packer M. Dual SGLT1 and SGLT2 inhibitor sotagliflozin achieves FDA approval: Landmark or landmine? Nat. Cardiovasc. Res. 2023;2:705– 707. doi: 10.1038/s44161-023-00306-x

DISCLAIMER

The information provided in this course is general in nature, and it is solely designed to provide participants with continuing education credit(s). This course and materials are not meant to substitute for the independent, professional judgment of any participant regarding that participant’s professional practice, including but not limited to patient assessment, diagnosis, treatment, and/or health management. Medical and pharmacy practices, rules, and laws vary from state to state, and this course does not cover the laws of each state; therefore, participants must consult the laws of their state as they relate to their professional practice.

Healthcare professionals, including pharmacists and pharmacy technicians, must consult with their employer, healthcare facility, hospital, or other organization, for guidelines, protocols, and procedures they are to follow. The information provided in this course does not replace those guidelines, protocols, and procedures but is for academic purposes only, and this course’s limited purpose is for the completion of continuing education credits.

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© RxCe.com LLC 2023: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.