Patty Taddei-Allen, PharmD, MBA, BCACP, BCGP

Hypertrophic cardiomyopathy (HCM) is often seen in patients as an autosomal dominant genetic heart disease with a variable clinical course. It is characterized by left ventricular hypertrophy, and with some patients, there is no evidence of a genetic etiology or presence of HCM in family members. Young age at diagnosis and the presence of a pathogenic or likely pathogenic sarcomere variant predict greater lifelong risk for stroke, heart failure, ventricular arrhythmia, atrial fibrillation, or mortality. Most individuals affected with HCM live to an average lifespan due to improvements in earlier diagnosis, sudden cardiac death risk stratification, family screening, pharmacologic therapy, devices, and invasive septal reduction therapy. Although these interventions have improved mortality, they are associated with significant costs and morbidities. There are burdensome costs related to genetic testing, family screening, implantable cardioverter-defibrillators, alcohol septal ablation, septal myectomy, pacemaker placement, and cardiac transplantation. In addition to these economic considerations, patients with HCM may experience a diminished health-related quality of life. Shared decision making between the patient and physician, use of multidisciplinary teams at HCM centers, and judicious use of exercise when appropriate have been shown to improve patient outcomes. Currently, treatments for HCM do not treat the underlying illness. Although not yet approved by the FDA, cardiac myosin inhibitors have recently shown promise in clinical trials to treat the underlying pathology of HCM. If approved by the FDA, managed care pharmacists should be ready to assess their safety and efficacy to improve the clinical burden and quality of life of those affected by HCM and reduce medical costs for these patients against standard of care. Long-term safety and efficacy data showing reductions in hospitalizations, morbidity, and mortality will be needed to determine their actual utility in managing HCM and ultimate place in therapy.

Hypertrophic cardiomyopathy (HCM) is often seen in patients as an autosomal dominant genetic heart disease that equally affects men and women with a heterogeneous clinical course. However, women are not diagnosed as frequently as men. The prevalence of asymptomatic HCM in young adults is approximately 1:200 to 1:500 in the United States. In adults, the incidence of symptomatic HCM based on medical claims data is less than 1:3000 adults in the United States. However, the real burden is much greater when accounting for undiagnosed disease in the general population. Assessment of HCM may be precipitated by the appearance of symptoms, an abnormal electrocardiogram during a routine physical examination, a cardiac event, detection of a heart murmur, or cardiac imaging during family screening studies.

HCM is a disorder characterized by left ventricular hypertrophy (LVH) not attributable to other cardiac, systemic, or metabolic causes with or without genetic evidence of a disease-causing sarcomere variant. A maximal end-diastolic wall thickness of 15 mm or greater anywhere in the left ventricle verified by imaging (cardiovascular magnetic resonance or 2D echocardiography) or 13-14 mm along with the presence of HCM in a family member or positive genetic test in the absence of other causes confirms a clinical diagnosis of HCM in adults.

Approximately 30% to 60% of patients with HCM have a detectable pathogenic or likely pathogenic genetic variant. Variants in one of eight or more genes encoding cardiac sarcomere proteins or sarcomere-related structures cause the LVH of HCM. The 2 most common pathogenic sarcomeric gene variants are myosin-binding protein C3 (

), present in 70% of variant-positive patients. Other genes (

) each account for about 1% to 5% of patients. Although family members with a pathogenic variant will likely develop clinical HCM, there is variability of age of disease occurrence.

Although some patients with HCM may have an average life expectancy without debilitating symptoms or need for devices/surgery, other patients may experience a more severe disease course. Patients with a pathogenic sarcomeric gene variant or those diagnosed with HCM early in life may be at a greater lifelong risk for stroke, heart failure (HF), ventricular arrhythmia, atrial fibrillation (AF), or mortality. Approximately 30% to 40 % of patients with HCM may experience HF symptoms associated with systolic dysfunction, AF with increased risk for thromboembolic stroke, progressive symptoms due to diastolic dysfunction or left ventricular outflow tract obstruction (LVOTO), or sudden cardiac death (SCD). Thirty percent of patients develop nonobstructive HCM (nHCM), while most patients develop obstructive HCM (oHCM) over time. HCM mortality rates have decreased to less than 1% per year with modern therapies, such as implantable cardiac defibrillators (ICDs) and alcohol septal ablation (ASA), and SCD risk-stratification strategies. Due to the decrease in SCD rates, HF is now the predominant cause of morbidity and mortality in patients with HCM.1

A study involving the international Sarcomeric Human Cardiomyopathy Registry provided additional insights into factors related to poorer outcomes. Patients with HCM aged 20 to 29 years and 50 to 69 years had a greater than 4 times and equal to or greater than 3 times mortality, respectively, than the general US population. A 77% (95% CI, 0.72-0.80) cumulative incidence of the overall composite outcome by 60 years occurred in patients younger than 40 years at diagnosis, compared with 32% (95% CI, 0.29-0.36) by age 70 years for patients diagnosed older than 60 years. The overall composite outcome was defined as the first occurrence of SCD, cardiac arrest, ICD implantation, cardiac transplantation (CT), left ventricular assist device (LVAD) implantation, New York Heart Association (NYHA) functional class III/IV symptoms, AF, stroke, and death. A pathogenic or likely pathogenic sarcomere genetic variant predicted greater than 2-fold increased risk for all outcomes, with the chance for ventricular arrhythmias being the highest (HR, 2.8; 95% CI, 2.1-3.9; 

<.001). AF and HF occurred most often, with the lifetime cumulative incidence of malignant ventricular arrhythmias occurring in 32% (95% CI, 0.23-0.40) in patients younger than 40 years at the age of diagnosis and in 1% (95% CI, 0.01-0.02) in patients older than 60 years.

Currently, there is no cure for HCM. Although pharmacologic therapy, devices, and surgical management effectively prolong lifespan and treat symptomatology of HCM, substantial costs accompany these interventions.

Evaluation of familial inheritance, including a 3-generation family history, is recommended by the HCM treatment guidelines as part of the initial assessment. Family history may be pertinent to the recommendation of subsequent genetic screening of the patient and at-risk family members. The clinical benefits of genetic testing in HCM include confirmation of the diagnosis, cascade genetic testing in family members, and guidance regarding reproductive decisions. Cascade genetic testing in family members identifies the individual carrying the pathogenic variant requiring ongoing clinical surveillance while releasing those without from lifelong surveillance.

The cost for genetic testing ranges from $3000 to $3800 for the first family member and $250 for other family members if a mutation is identified.

 Unfortunately, there is little consensus among medical payers in the United States on coverage for the genetic screening tests. In addition, different payers will include different panels for the same condition. Often, the medical policy, if it exists and is available to clinicians and patients, the requirement of “medical necessity” is often not determined until after a claim has been submitted.

An Australian study investigating the cost-effectiveness of genetic and clinical screening compared with clinical screening alone concluded that the addition of genetic testing was a very cost-effective strategy with an incremental cost-effectiveness ratio of 587 Euro per quality-adjusted life-year (QALY) gained and 9509 Euro per additional life-year gained as determined by a probabilistic Markov decision model.

To evaluate the financial burden of oHCM on the healthcare system, a retrospective cohort study examined National In-patient Sample (NIS) records of 2605 patients admitted to the hospital with oHCM in the United States in 2013. Thirty-three percent of the patients included in the analysis were older than 64 years, 18% were younger than 45 years, and most were female (55%). The average stay was 4.9 days, with the majority (81.19%) of patients treated in urban teaching hospitals. The study defined hospital charges as the amount the hospital charged for the entire hospital stay, excluding professional fees. Researchers converted total charges to costs using cost-to-charge ratios based on hospital accounting reports from the Centers for Medicare & Medicaid Services (CMS). The mean and median cost of admission was $25,433 and $19,422, respectively. The actual mean and median hospital charges were $88,646 and $58,460, respectively. Comparatively, this was much higher than the reported 2014 US healthcare spending of $9523 per person when the study was conducted. Private insurance paid for approximately 43% of the hospitalizations, Medicare for 37%, and Medicaid for 10%. The percentage of routine discharge was inversely proportional to age, declining from 90% to 65% from age 18 to 85. Most patients were discharged to home (76.39%), but a substantial remainder required further institutionalized care (13.05% home health care, 4.61% nursing home care, and 3.45% short-term hospital care).

Another study specifically examined the impact of arrhythmias in patients with HCM on the cost of hospitalization and mortality. Using NIS data of 225,816 hospitalizations of patients with HCM from 2003 to 2014, the study found a 10.5% relative increase (

<.001) in the number of hospitalizations related to arrhythmias in patients with HCM, especially in patients with more comorbidities and aged 80 years or older. The total mean cost of care in patients with HCM and arrhythmia after adjusting for inflation rose from $16,105 in 2003 to $19,310 in 2014 (

-trend, <.001), representing an absolute increment in annual national cost from $125 million in 2013 to $162 million in 2014 (

-trend, <.001). The overall mean cost of HCM hospitalization with arrhythmia was $20,522 versus $15,636 with no arrhythmia, with ventricular fibrillation/flutter (VF/VFL) ($39,108) and ventricular tachycardia ($28,996). In patients with HCM and arrhythmias, in-hospital mortality was higher than those without arrhythmias. Still, there was a significant decrease in mortality rate in patients with HCM and arrhythmias from 6.2% in 2003 to 3.4% in 2014 (

trend, <.001). In patients with HCM and arrhythmias, the mortality rate was highest in patients aged 80 years or older (7.4%), females (5.5%), and in Black (4.64%).

Alcohol Septal Ablation (ASA) or Septal Myectomy (SM)

Patients with HCM and symptomatic LVOTO refractory to medications may require invasive septal reduction therapy (SRT) with either ASA or SM. Each intervention is effective but has certain associated risks and benefits (Table1). Complete heart block as a result of SRT may require a permanent pacemaker in some patients post-procedure.1 In 2014, the mean hospital charge in the United States associated with a pacemaker was $83,521, with an in-hospital death rate of 1.46% and a mean length of hospital stay of 5.1 days.

A study using the US National Readmission Database compared resource utilization, in-hospital mortality, and complication rates between the 2 age groups of patients with HCM undergoing ASA or SM. A total of 2245 patients with HCM underwent ASA (1272 patients ≤65 years, 973 patients >65 years) and 2113 patients SM (1739 patients ≤65 years, 374 patients >65 years) from 2010 to 2015. The median length of hospital stay was significantly longer (SM, 6 days vs ASA, 3 days; 

 <.001) in both age groups, and the total median hospital costs were greater (≤65 years: SM, $28,459 vs ASA, $13,847; 

<.001; >65 years: SM, $32,429 vs ASA, $15,343; 

<.001) in both age groups receiving SM versus ASA. The in-hospital mortality in patients undergoing SM was significantly greater in both age groups compared with patients undergoing ASA (≤65 years: SM, 1.5% vs ASA, 0.3%; OR, 6.2; 95% CI, 1.01-38.00; 

= .048) (>65 years: SM, 6.7% vs ASA, 1.7%; OR, 4.29; 95% CI, 1.03-17.9; 

Although the initial resource utilization and costs were lower with ASA than SM, post-procedural healthcare utilization and costs associated with ASA may increase over time compared with SM. Another study examined claims data from the OptumLabs Data Warehouse of adult patients with oHCM from 2006 to 2018, comparing the 2-year cumulative post-procedural costs and healthcare utilization after SM and ASA. A total of 379 patients underwent SM and 185 ASA, with 53% being male and of the mean age of 56.3. There was a statistically insignificant increase in the 2-year mean number of physician office visits (20 SM vs 23.4 ASA) or emergency department visits (IRR, 1.16; 95% CI, 0.76-1.77) in patients undergoing ASA versus SM. The 2-year risk of hospital readmission was similar between the 2 groups (36.9% following SM and 43.8% following ASA). There was a nonsignificant increase in readmissions in the ASA group versus the SM group (IRR 1.54; 95% CI, 0.99-2.40). The median cumulative 2-year post-procedural costs were higher in those receiving ASA ($22,165 [range, $8848-$81,143]) versus SM ($20,170 [range, $10,006-$44,755]). Rehospitalization accounted for approximately 20% (for ASA) and 17% (for SM) of these post-procedural costs.

Implantable Cardiac Defibrillator and Short Atrioventricular Delay Pacing

An ICD has proven efficacy in aborting potentially life-threatening ventricular tachyarrhythmias and preventing SCD in patients with HCM. HCM guidelines recommend using ICD as primary prevention based on risk factors and secondary prevention in individuals surviving a cardiac arrest or hemodynamically significant ventricular fibrillation/ventricular tachycardia.1 An ICD system can deliver anti-tachycardia pacing, bradycardia pacing, cardioversion, and can be combined with cardiac resynchronization therapy when advised.9 The mean hospital charges in the United States in 2014 for an implantable defibrillator were $171,476, with an in-hospital death rate of 0.69% and a mean length of stay of 6.3 days.

A Swedish study simulated the cost-effectiveness of an ICD over 12 years in terms of costs per life saved and cost per gained QALY versus treatment without an ICD in adults with HCM. The mean age of ICD implantation was 51.8 years based on data from a nationwide HCM cohort. The assumed willingness-to-pay for a gained QALY was 53,050 Euro. The number of lives saved was 402 of the 1000 simulated patients after 12 years, and 2.5 patients needed to be treated during the 12 years to save one life. The cost per life saved is approximately 57,117 Euro, and the incremental cost for a gained QALY was 15,150 Euro. From the societal perspective, including effects on productivity losses, in terms of QALYs, ICD treatment was superior and less expensive.

Short atrioventricular delay-pacing is a treatment alternative to SRT for the treatment of LVOTO in oHCM. The long-term-hemodynamic results associated with short atrioventricular delay-pacing are not inferior to myectomy, but no long-term randomized studies comparing it with SRT in comparable patient groups exist. A Swedish case-control study compared the outcomes of 31 pairs of patients with oHCM treated with myectomy or pacing from 2002 to 2013. Both treatments resulted in significant improvements in LVOT-gradients as well as NYHA class. The mean cost of hospitalization was significantly less for pacing than myectomy: 74,000 (≈$11,111 in 2013 USD) ± 16,000 (≈$2,402 in 2013 USD) Swedish krona (SEK) for pacing and 310,000 (≈$46,546 in 2013 USD) ± 180,000 (≈$27,027 in 2013 USD) SEK for myectomy, 

<.001), with a significantly shorter in-hospital stay (2 days vs 7 days). The myectomy group had significantly more peri-procedural complications than the pacing group (35.5% vs 3.2%, respectively; 

<.0001). A pacemaker was implanted in 9.7% of patients peri-operatively and in 25.8% in late-follow up in the myectomy group. Freedom from re-interventions was observed in 61.3% in the myectomy group versus 90.3% in the pacing group (

Cardiac Transplantation (CT)/Ventricular Assist Devices (VADs)

A specific subset of patients with HCM may experience severe refractory congestive HF that ultimately requires CT. About 3.5% of patients may progress to a burnt-out end-stage distinguished by fibrotic replacement and chamber remodeling, causing systolic dysfunction and restrictive ventricular filling with a mean 3-year survival time. A heart transplantation is a life-saving intervention in patients with end-stage HCM. It is the only option to restore functional status and longevity among HCM patients with advanced HF.

 However, CT is very costly and has associated risks and morbidities. The mean hospital charges in the United States in 2014 for CT were $808,770, with an in-hospital death rate of 7.84% and mean length of stay of 45.4 days.

 Heart transplantation also requires the lifetime use of immunosuppressant medications. About 10% of heart transplant recipients need renal replacement therapy or transplant due to calcineurin inhibitor-induced nephrotoxicity. Right HF and biventricular failure may occur early postoperatively. Heart transplant recipients may also experience rejection and infectious complications. Coronary vasculopathy, requiring re-transplantation, develops in about 30% to 40% of heart transplant recipients within 5 years. Malignancy post-transplantation accounts for 10% to 23% deaths post-transplantation.

 A study of evaluating outcomes in 535 adult HCM patients in the United States registered in the Scientific Registry of Transplant recipients with HCM awaiting a heart transplant between April 2008 and October 2016 determined the waitlist mortality was 9.6%. The 12-month heart transplant rate was 64.8%, and post-transplant survival in patients with HCM was 91.6% at one year and 82.5% at 5 years.

 Bridge to transplantation (BTT) with an implantable VAD may be used in patients with HCM, but is difficult because of placement challenges due to small left ventricular chamber size, the presence of LVH (mid and distal left ventricular), and left ventricular muscle bundles, which could impede proper functioning. By report, VAD placement in patients with HCM may increase susceptibility to right ventricular dysfunction and hypotension. Many patients with HCM may not qualify for VAD placement, which may place them at a lower priority on the transplant list.

In addition to the economic costs accompanying treatment interventions for HCM, reduced HRQOL in patients living with HCM has been demonstrated in studies. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a self-administered validated questionnaire measuring the perceived burden of HF symptoms. Scores range from 0 to 100, with higher values representing better HRQOL. A study in 91 patients with HF and HCM evaluated the HRQOL (57% males; median age 58) and found an overall moderate HRQOL impairment (median global KCCQ score, 67). NYHA class and the median global KCCQ score were inversely correlated (Kendall’s tau b coefficient r−0.33; 

= .001). There were also significantly worse HRQOL scores in patients with pulmonary hypertension (resting pulmonary artery systolic pressure ≥45 mm Hg) than those without (median KCCQ score, 56.2 vs 77.5; 

= .013). Patients with a worse HRQOL score were older and had more severe functional impairment. These included a history of syncope, poor renal function, echocardiographic parameters of increased severity and/or dysfunction, and elevated pulmonary artery systolic pressure. The study identified estimated glomerular filtration rate and NYHA functional class as independent predictive factors of the HRQOL score.

A study conducted between 2015 and 2018 used a conceptual model to capture patients’ perspectives on the symptoms of HCM they were experiencing and their impact on their lives. A total of 444 participants who responded to the 80-question web survey reported symptoms of fatigue (74%), shortness of breath upon exertion (73%), lightheadedness (70%), exercise intolerance (57%), palpitations (54%), dizziness after exertion (54%), chest pain (39%), and syncope (24%). The impact of physical activity upon symptoms varied, with the majority reporting slight (42%) or marked limitation (31%) of activity, and 6% reported being unable to be physically active without discomfort per survey. Eighty-four percent of patients with oHCM reported 4 or more symptoms compared with 55% of patients with nHCM. The majority of patients (70%) experienced symptoms somewhat or significantly worsening since diagnosis, having a more significant impact on their ability to work. The most commonly reported effects of HCM elicited during the concept elicitation interviews of 27 patients included emotional impacts (78%), restrictions of physical activities (78%), feelings of depression and anxiety (78%), and limitations on work (63%).

HRQOL has also been shown to be impacted in patients with HCM and an ICD in a Swedish study. The study used a validated self-reported questionnaire (36-item short form). It analyzed the responses of 245 patients with HCM and an ICD, comparing responses with a Swedish age- and sex-matched control group. The physical functioning, role physical, general health, vitality, social functioning, role emotional, mental health, physical component summary, and mental component summary scores were significantly lower (

<.001) than control (Figure 118). The most considerable impact occurred in the general health domain, with a more significant effect seen in the physical component summary scores than the mental component summary scores. Subgroup analyses showed that AF or HF significantly impacted physical functioning, physical role, and general health. AF also had a significant impact on social functioning scores. Inappropriate ICD shock negatively impacted mental health while appropriate ICD therapy trended oppositely. The HRQOL was similar between primary and secondary prevention.

Crucial to improving patient outcomes is shared decision making. Adherence to recommendations can be enhanced when there is patient involvement in the treatment decision-making process. There should be a dialogue between patients and their healthcare providers informing them of the available testing and treatment options, including discussing all the risks and benefits. A patient should be encouraged to express their goals and concerns. The selection of interventions, including genetic evaluation, activity, lifestyle, and therapy choices, should be based on individual values, preferences, and associated conditions and morbidities. Judicious use of exercise, when advised, can also improve outcomes. Referral of patients to multidisciplinary HCM centers may help improve patient outcomes. Providers at HCM centers have specific training and competencies necessary to manage these patients’ specialized and complex needs. Particularly with invasive SRT (ASA or SM), treatment guidelines recommend that patients have the procedure performed at comprehensive or primary HCM centers with specialized training and sufficient volumes to ensure optimal outcomes.

Emerging Therapies: Cardiac Myosin Inhibitors

Currently, no medical treatments that modify the pathology and disease course exist for HCM. Gene therapy with clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9 (CRISPR/Cas9), exon-skipping, trans-splicing, gene replacement, or small interfering RNAs (siRNAs) may play a future role in the treatment of HCM.

 Trials investigating small molecules, such as cardiac myosin inhibitors, in patients with HCM have shown promise. The phase 2 trial (REDWOOD-HCM) with CK274 is currently ongoing.20 Cardiac myosin inhibitors selectively inhibit cardiac myosin ATPase and reduce myocardial contractility by decreasing the available number of actin-myosin cross-bridges. The reduction in contractility reduces the outflow gradient, which may improve symptoms.

On January 11, 2021, the FDA granted CK274 an orphan drug designation for the treatment of symptomatic HCM.

 Investigations with the cardiac myosin inhibitor mavacamten completed phase 2 clinical trial testing (MAVERICK-HCM) in patients with symptomatic nHCM and phase 3 clinical trial testing (EXPLORER-HCM) in patients with symptomatic oHCM.

 On July 23, 2020, the FDA granted breakthrough therapy designation to mavacamten to treat symptomatic oHCM with a New Drug Application (NDA) submission expected in the first quarter of 2021.

 An ongoing long-term extension study, MAVA-LTE, evaluating the long-term safety of mavacamten is estimated for completion in November 2025.

 These investigational therapies that target the underlying pathophysiology of HCM are not approved by the FDA yet.

Currently, medication therapy in patients with HCM is first-line for symptomatic control (see Figure 21,27). The recommended management of HCM includes the use of low-cost generically available cardiac medications such as non-dilating β-blockers, non-dihydropyridine calcium channel blockers, and disopyramide. Other drugs may be used to treat HCM-associated complications, including anticoagulants for AF, antiarrhythmics for arrhythmias, and angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, and diuretics to treat HF. Patients refractory to treatment may require an ICD, SRT, or CT to treat symptoms and complications. See Figure 2 for current management of HCM.

As new treatments are approved, further clinical evidence regarding their safety and efficacy is gathered before place in therapy is determined by clinical practice guidelines. Expedited FDA approval is based on data from clinical studies conducted over a shorter timeframe, sometimes raising concerns of long-term safety and efficacy.

 This poses challenges for managed care professionals to allocate healthcare resource utilization responsibly and effectively. The development of informed and updated formulary strategies to treat HCM is essential to integrate pharmaceutical advances based on improved risk-benefit profiles of investigational agents.

 A clinically rigorous analysis of current clinical trial data should be conducted, looking for meaningful improvement on clinically significant end points, including hospitalization and mortality, as well as hemodynamic parameters.

 A review of available literature, including clinical treatment guidelines, pharmacoeconomic studies, and outcomes data, is essential. Other important points of consideration include analysis of FDA prescribing information and safety data, drug and total healthcare cost data, and efficacy and cost comparisons to standard of care. Comparative effectiveness data, if available, may be a valuable resource to evaluate the use of drug versus alternative treatment options. An effective formulary management process enables the managed healthcare system to discriminate between a clinically superior and a marginally effective drug, minimizing overall medical cost and promoting patient access to affordable care.

Utilization management strategies such as step therapy, quantity limits, and prior authorization (PA) may complement formulary management. Evidence-based PA criteria are crucial to ensure patients receive the most appropriate medication for their condition while reducing unnecessary drug use and cost. This will be more evident as new agents enter the marketplace, but even among current generically available agents, there are opportunities for enhanced utilization management to influence usage to less expensive generic agents.

HCM is a disease associated with substantial economic and clinical burdens. Although improvements in earlier diagnosis, risk stratification, family screening, pharmacologic therapy, devices, and surgical management have led to better outcomes, HCM has been associated with a decreased HRQOL and psychological well-being. Thus far, management of HCM has been symptomatic and does not treat the underlying illness. Cardiac myosin inhibitors have recently shown promise in clinical trials as potential first-in-class medications to treat the underlying pathology of HCM. Managed care pharmacists should be prepared to assess their value to improve patients’ length and quality of life affected by HCM and reduce medical costs for these patients. Ultimately, the results of long-term safety and efficacy studies showing reductions in hospitalizations, morbidity, and mortality compared with standard of care will determine these agents’ value and place in practice.

 Patty Taddei-Allen, PharmD, MBA, BCACP, BCGP, is the Vice President, Clinical Programs and Services, WellDyne, Lakeland, FL.

 This activity is supported by an educational grant from MyoKardia, Inc, a wholly owned subsidiary of Bristol Myers Squibb.

 Dr Taddei-Allen has no relevant financial relationships with commercial interests to disclose.

 Concept and design; drafting of the manuscript; and critical revision of the manuscript for important intellectual content.

Medical writing and editorial support provided by: 

1. Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2020;76(25):3022-3055. doi: 10.1016/j.jacc.2020.08.044

2. Ho CY, Day SM, Ashley EA, et al. Genotype and lifetime burden of disease in hypertrophic cardiomyopathy: insights from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Circulation. 2018;138(14):1387-1398. doi: 10.1161/CIRCULATIONAHA.117.033200

3. Genetic testing for hypertrophic cardiomyopathy: special considerations. Hypertrophic Cardiomyopathy Association. Accessed January 24, 2021. www.4hcm.org/content.asp?contentid=187#:~:text=If%20a%20person%20chooses%20to,rate%20that%20is%20around%20%24250

4. Jan A, Shah MA, Rehman S, Rungatscher A, Ahmed N, Faggian G. Hypertrophic obstructive cardiomyopathy and the cost of treatment. EJCM. 2016;4(2):27-32. doi: 10.15511/ejcm.16.00227

5. Tripathi B, Khan S, Arora S, et al. Burden and trends of arrhythmias in hypertrophic
cardiomyopathy and its impact of mortality and resource utilization. J Arrhythm. 2019;35(4):612-625. doi: 10.1002/joa3.12215

6. Lemor A, Villablanca PA, Hosseini Dehkordi SH, et al. Comparison of outcomes of alcohol septal ablation or septal myectomy for hypertrophic cardiomyopathy in patients ≤65 years versus >65 years. Am J Cardiol. 2020;127:128-134. doi: 10.1016/j.amjcard.2020.04.018

7. Sun D, Schaff H, Van Houten HK, et al. Health care utilization and costs of surgical septal myectomy and alcohol septal ablation for obstructive hypertrophic cardiomyopathy. CF2 Abstract. Western Thoracic Surgical Association 46th Annual Meeting. June 24-27, 2020. Accessed March 31, 2021. https://meetings.westernthoracic.org/abstracts/2020/CF2.cgi

8. Virani SS, Alonso A, Benjamin EJ, et al; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics−2020 update: a report from the American Heart Association. Circulation. 2020;141(9):e139-e596. doi: 10.1161/CIR.0000000000000757

9. Magnusson P, Wimo A. Health economic evaluation of implantable cardioverter defibrillators in hypertrophic cardiomyopathy in adults. Int J Cardiol. 2020;311:46-51. doi: 10.1016/j.ijcard.2020.02.055

10. Javidgonbadi D, Andersson B, Abdon NJ, Östman-Smith I. Morbidity and resource usage after myectomy- or pacing-treatment in hypertrophic obstructive cardiomyopathy: a case-control study. Int J Cardiol. 2021;322:197-203. doi: 10.1016/j.ijcard.2020.08.066

11. Spoonamore KG, Johnson NM. Who pays? Coverage challenges for cardiovascular genetic testing in US patients. Front Cardiovasc Med. 2016;3:14. doi: 10.3389/fcvm.2016.00014.

12. Ingles J, McGaughran J, Scuffham PA, Atherton J, Semsarian C. A cost-effectiveness model of genetic testing for the evaluation of families with hypertrophic cardiomyopathy. Heart. 2012;98(8):625-630. doi: 10.1136/heartjnl-2011-300368

13. PoundSterlingLive.com. Historical rates for the USD/SEK currency conversion on November 13, 2013. Accessed March 27, 2021. poundsterlinglive.com/best-exchange-rates/us-dollar-to-swedish-krona-exchange-rate-on-2013-11-13

14. Torres MF, Perez-Villa F. Heart transplantation in patients with hypertrophic cardiomyopathy. Glob Cardiol Sci Pract. 2018;2018(3):32. doi: 10.21542/gcsp.2018.32

15. Zuñiga Cisneros J, Stehlik J, Selzman CH, Drakos SG, McKellar SH, Wever-Pinzon O. Outcomes in patients with hypertrophic cardiomyopathy awaiting heart transplantation. Circ Heart Fail. 2018;11(3):e004378. doi: 10.1161/CIRCHEARTFAILURE.117.004378

Articles

Hypertrophic Cardiomyopathy Considerations for the Managed Care Pharmacist

Diabetes represents a major and growing challenge. It is estimated to affect 34 million US adults, with type 2 diabetes (T2D) accounting for more than 90% of cases.

 There are substantial downstream consequences of uncontrolled T2D, including microvascular complications that place patients at risk of chronic kidney disease, diabetic retinopathy, and diabetic neuropathy.

 As a result, diabetes is a leading cause of kidney failure, blindness, and lower-extremity amputations.

 In addition, the risk of cardiovascular disease (CVD) is increased 2- to 3-fold by the presence of T2D,

 with CVD being the leading cause of death in this population.


As a consequence of the high prevalence of T2D and downstream complications, T2D imposes a substantial burden on US health care systems. Early and improved glycemic control can lead to lower health care costs, and reduce the lifetime risk of developing complications.

 In patients with newly diagnosed T2D, failure to attain early glycemic control has been associated with increased microvascular and macrovascular events, and an increased risk of death.

 Thus, early achievement of glycemic control (within 1 year of a T2D diagnosis) is important to reduce the risk of long-term complications in T2D.

 An array of glucose-lowering therapies are now available to help achieve this, and these agents are administered across a range of patient populations at varying stages of the disease trajectory.


This supplement presents key information for those working in the managed care setting, provides an up-to-date synopsis of the burden of T2D in the United States, and reviews the role of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the management of T2D, before appraising the clinical evidence for the first oral GLP-1RA, oral semaglutide. Drawing on data from the phase 3a PIONEER clinical trial program, which generated data for oral semaglutide in over 9500 patients with T2D in a range of clinical settings, we explore the efficacy of oral semaglutide in terms of glycemic control and body weight, assess cardiovascular (CV) outcomes, discuss the safety and tolerability profile of oral semaglutide, and describe patient-reported outcomes. Throughout, the clinical evidence for oral semaglutide is placed in context with that available for other therapeutic options, including injectable GLP-1RAs.

 Drs Dougherty and Heile review the burden of T2D in the United States, emphasizing the high direct medical costs related to diabetes (estimated to total $237 billion in the United States in 2017), which are primarily driven by prescription medication costs for antidiabetic agents, hospital inpatient and outpatient care, and physician office-based care, and describe indirect costs.

 This socioeconomic burden is compounded by a further $90 to $250 billion in indirect costs, such as lost productivity.

 The authors also explore the role of GLP-1RAs and the challenges of clinical inertia and poor adherence, and the rationale for an oral GLP-1RA, in the context of considerations for managed care.


GLP-1RAs have been in clinical use for over a decade,

 and are associated with high glucose-lowering efficacy and neutral or low risk of hypoglycemia, and promote weight loss.

 Despite these known benefits, they remain a relatively underutilized class of medication,

 which may relate in part to the injectable route of administration and their relatively high cost.

 In light of this, the 2019 approval of the first tablet formulation of a GLP-1RA, oral semaglutide,

 could lead to earlier and more widespread use of the GLP-1RA modality.


To select the most appropriate therapy for each patient and tailor treatment for those with pre-existing conditions such as CVD, it is important to consider not only glycemic control and body weight, but the drug’s safety profile and other factors, such as patient preferences and costs.

 Drs Rodbard, Dougherty, and Taddei-Allen describe the PIONEER phase 3a clinical trial program with a focus on the efficacy results and their implications for managed care specialists. Several GLP-1RAs have been shown to reduce the risk of CV events in T2D, and they are recommended in patients with established CVD, and in those at high risk of CVD.

 Drs Lingvay, Taddei-Allen, and Dougherty review the evidence for CV outcomes with oral semaglutide, explore the safety profile of oral semaglutide across the clinical trial program, and discuss its use in specific patient populations.


Beyond these clinical outcomes, T2D significantly impairs patients’ health-related quality of life (HRQOL), affecting physical and mental functioning, and social interactions.

 The development of complications or coexistence of comorbidities are significant contributors to the negative impact of T2D on HRQOL, as are weight gain and episodes of hypoglycemia (typically associated with insulin or insulin secretagogue use).

 The assessment of patient-reported outcomes is increasingly utilized in clinical trials, and it can complement clinical outcomes and significantly contribute to treatment decisions in daily practice. The final article

 by Drs Schneider, Taddei-Allen, and Dougherty focuses on patient experiences, reflecting on how patient-reported outcomes can inform decision-making in managed care, and examines the effect of oral semaglutide on such outcomes. 


This article was supported by Novo Nordisk Inc; the company was provided with the opportunity to perform a medical accuracy review. Under the direction of the authors, medical writing and editorial support was provided by Nicole Cash of Axis, a division of Spirit Medical Communications Group Limited (funded by Novo Nordisk Inc).

 TriHealth Physician Partners (MH); WellDyne (PTA).


Financial support for this work was provided by Novo Nordisk Inc.


Dr Heile has served as a speaker for and holds stock in Novo Nordisk Inc. Dr Taddei-Allen is an advisory board member for Novo Nordisk Inc.


Drafting of the manuscript (MH, PTA); critical revision of the manuscript for important intellectual content (MH, PTA); responsibility for content (MH, PTA).


Michael Heile, MD, FAAFP, 6331 Glenway Ave, Cincinnati, OH 45211. Email: Michael_Heile@trihealth.com. Phone: +1 513 389 1400.

1. Centers for Disease Control and Prevention. National diabetes statistics report, 2020: estimates of diabetes and its burden in the United States. Centers for Disease Control and Prevention, U.S. Department of Health and Human Services. 2020. Accessed April 7, 2020. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf

2. American Diabetes Association. 11. Microvascular complications and foot care: Standards of Medical Care in Diabetes-2020. 

. 2020;43(suppl 1):S135-S151. doi:10.2337/dc20-S011

3. Al-Salameh A, Chanson P, Bucher S, et al. Cardiovascular disease in type 2 diabetes: a review of sex-related differences in predisposition and prevention. 

. 2019;94(2):287-308. doi:10.1016/j.mayocp.2018.08.007

4. American Diabetes Association. Economic costs of diabetes in the U.S. in 2017. 

. 2018;41(5):917-928. doi:10.2337/dci18-0007

5. Bansal M, Shah M, Reilly B, et al. Impact of reducing glycated hemoglobin on healthcare costs among a population with uncontrolled diabetes. 

. 2018;16(5):675-684. doi:10.1007/s40258-018-0398-2

6. Laiteerapong N, Ham SA, Gao Y, et al. The legacy effect in type 2 diabetes: impact of early glycemic control on future complications (the Diabetes & Aging Study). 

. 2019;42(3):416-426. doi:10.2337/dc17-1144

7. American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes-2020. 

. 2020;43(suppl 1):S98-S110. doi:10.2337/dc20-S009

8. Dougherty T, Heile M. Type 2 diabetes in the US managed care setting: the burden of disease and rationale for an oral glucagon-like peptide-1 receptor agonist. 

. 2020;26(suppl 16):S325-S334. doi:10.37765/ajmc.2020.88552

9. Shrestha SS, Honeycutt AA, Yang W, et al. Economic costs attributable to diabetes in each U.S. state. 

. 2018;41(12):2526-2534. doi:10.2337/dc18-1179

10. Nauck MA, Meier JJ. Management of endocrine disease: are all GLP-1 agonists equal in the treatment of type 2 diabetes? 

. 2019;181(6):R211-R234. doi:10.1530/EJE-19-0566

11. Garber AJ, Handelsman Y, Grunberger G, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2020 Executive Summary. 

. 2020;26(1):107-139. doi:10.4158/CS-2019-0472

12. Montvida O, Shaw J, Atherton JJ, et al. Long-term trends in antidiabetes drug usage in the U.S.: real-world evidence in patients newly diagnosed with type 2 diabetes. 

. 2018;41(1):69-78. doi:10.2337/dc17-1414

13. Spain CV, Wright JJ, Hahn RM, et al. Self-reported barriers to adherence and persistence to treatment with injectable medications for type 2 diabetes. 

. 2016;38(7):1653-1664.e1. doi:10.1016/j.clinthera.2016.05.009

14. FDA approves first oral GLP-1 treatment for type 2 diabetes. News release. U.S. Food & Drug Administration. September 20, 2019. Accessed June 1, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-glp-1-treatment-type-2-diabetes

15. Rodbard HW, Dougherty T, Taddei-Allen P. Efficacy of oral semaglutide: overview of the PIONEER clinical trial program and implications for managed care. 

. 2020;26(suppl 16):S335-S343. doi:10.37765/ajmc.2020.88554

16. Lingvay I, Taddei-Allen P, Dougherty T. Cardiovascular outcomes, safety, and tolerability with oral semaglutide: insights for managed care. 

. 2020;26(suppl 16):S344-S355. doi:10.37765/ajmc.2020.88555

17. Trikkalinou A, Papazafiropoulou AK, Melidonis A. Type 2 diabetes and quality of life. 

. 2017;8(4):120-129. doi:10.4239/wjd.v8.i4.120

18. Pawaskar M, Iglay K, Witt EA, et al. Impact of the severity of hypoglycemia on health - related quality of life, productivity, resource use, and costs among US patients with type 2 diabetes. 

. 2018;32(5):451-457. doi:10.1016/j.jdiacomp.2018.01.012

19. Marrett E, Stargardt T, Mavros P, Alexander CM. Patient-reported outcomes in a survey of patients treated with oral antihyperglycaemic medications: associations with hypoglycaemia and weight gain. 

. 2009;11(2):1138-1144. doi:10.1111/j.1463-1326.2009.01123.x

20. Schneider D, Taddei-Allen P, Dougherty T. The importance of patient-reported outcomes in type 2 diabetes: insight from the PIONEER program with oral semaglutide. 

. 2020;26(suppl 16):S356-S367. doi:10.37765/ajmc.2020.88556

The Evidence for Oral Semaglutide in Type 2 Diabetes From a Managed Care Perspective

The first tablet formulation of a glucagon-like peptide-1 receptor agonist(GLP-1RA), oral semaglutide, was approved in September 2019 for thetreatment of adults with type 2 diabetes (T2D). This article reviews datafrom the PIONEER phase 3a clinical trial program, which assessed theefficacy and safety of oral semaglutide in more than 9500 patients atdifferent stages on the disease trajectory (mean diabetes duration,3.5-15 years) and on a range of background treatment regimens(monotherapy, added to 1 or 2 oral glucose-lowering agents, or added toinsulin). The studies compared oral semaglutide (doses of 3 mg, 7 mg, or14 mg) with placebo, and selected commonly used glucose-loweringagents (empagliflozin 25 mg, sitagliptin 100 mg, or liraglutide 1.8mg). Across the studies, oral semaglutide provided greater glycatedhemoglobin (A1C) reductions than placebo, empagliflozin, or sitagliptinat 26 weeks, and similar A1C reductions as liraglutide. The proportion ofpatients achieving the A1C level recommended by the American DiabetesAssociation of less than 7.0% (53 mmol/mol) was greater with oralsemaglutide (7 mg, 42%-69%; 14 mg, 55%-77%) than placebo (7%-31%)and active comparators (25%-62%), with durable target achievement.Oral semaglutide was associated with similar reductions in body weightas empagliflozin and greater reductions than placebo, sitagliptin, orliraglutide. Oral semaglutide was also efficacious in patients with T2Dand moderate renal impairment. These findings indicate that oralsemaglutide presents a valuable option for treating patients with T2D in amanaged care setting, with the potential to expand the number of patientsbenefiting from GLP‑1RAs.

For author information and disclosures, see end of text.

Current Use of Glucagon-like Peptide-1 Receptor Agonists


Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a well-established treatment for type 2 diabetes (T2D), offering effective glycemic control, weight loss, and a low risk of hypoglycemia.

 Both the American Diabetes Association (ADA) Standards of Medical Care in Diabetes and the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) consensus statement recommend a GLP-1RA or a sodium–glucose cotransporter 2 inhibitor (SGLT2i) over alternative options such as a dipeptidyl peptidase-4 inhibitor (DPP-4i), a thiazolidinedione (TZD), or a sulfonylurea (SU) for the second-line treatment of patients with inadequate glycemic control on metformin, with the AACE/ACE consensus statement indicating preference for a GLP-1RA over an SGLT2i.

 In addition, the AACE/ACE consensus statement advocates a GLP-1RA or an SGLT2i as the preferred first-line treatment option for patients with, or at high risk of, atherosclerotic cardiovascular disease (CVD), chronic kidney disease, or heart failure.


Over the last 10 to 15 years, GLP-1RAs have become well established as an efficacious treatment option for patients with T2D, and provide both effective glycemic control and weight loss, but also have a well-characterized safety profile. Until September 2019, GLP‑1RAs were only available for administration by subcutaneous injection twice daily (exenatide

). However, in US analyses of claims data, only 5.4% of adult patients with T2D without CVD, and 4.1% with T2D and established CVD, were prescribed a GLP-1RA.

 The authors suggested a possible reason was that some patients experienced challenges in attaining newer classes of antidiabetic therapies, for example, due to medication cost and high-deductible health care plans. The low rates of GLP-1RA utilization may also be in part because, until recently, all GLP-1RAs were administered by subcutaneous injection, a route that may be less preferable to some patients compared with oral administration.

 As such, an oral GLP-1RA could potentially aid initiation of this class of drug earlier in the diabetes treatment trajectory.


Oral semaglutide, the first GLP-1RA developed as a tablet, was approved by the FDA in September 2019 to improve glycemic control in adults with T2D,

 and has since received approval in the European Union, United Kingdom, and Japan.

 This article describes the PIONEER phase 3a clinical trial program, which generated data on oral semaglutide in over 9500 patients with T2D in a range of clinical settings, with a focus on the efficacy results and their implications for managed care specialists.

Overview of the PIONEER Clinical Trial Program


The comprehensive global PIONEER program included patients who were representative of those typically encountered in clinical practice (

 Common inclusion criteria for the PIONEER trials were at least 18 years old, a diagnosis of T2D at least 90 days prior to screening, and inadequate glycemic control, with an A1C level within the range of 7.0% to 9.5% (53-80 mmol/mol),

 depending on the trial. The various trials assessed the effects of oral semaglutide 3, 7, and 14 mg in patients across the wide spectrum of the T2D disease course. Oral semaglutide was initiated at a dose of 3 mg for all patients, before escalating to 7 mg after 4 weeks, and then to 14 mg after a further 4 weeks depending on the treatment arm.

 PIONEER 7 was an exception: patients were initiated at a 3-mg dose and after 8-week intervals the dose could then be increased or decreased, as described earlier.

 Patients with early T2D (mean diabetes duration, 3.5 years) managed on diet and exercise only were studied in PIONEER 1.

 Effects in patients with more established T2D (mean diabetes duration, 7.4 years) already receiving 1 or 2 oral glucose-lowering agents were studied in: PIONEER 2 (metformin only); PIONEER 3 (metformin ± SU); PIONEER 4 (metformin ± SGLT2i); and PIONEER 7 (1 or 2 oral agents including metformin, SU, TZD, or SGLT2i).

 Patients with advanced disease (mean diabetes duration, 15.0 years) taking insulin (basal, basal-bolus, or premixed; with or without metformin) who required additional treatment were studied in PIONEER 8.

 Further studies were conducted in the settings of renal impairment (PIONEER 5),


Four trials compared oral semaglutide with commonly used glucose-lowering agents from drug classes recommended for patients who require further treatment intensification, namely, the SGLT2i, empagliflozin (PIONEER 2), the DPP-4i, sitagliptin (PIONEER 3 and 7), and the once-daily injectable GLP-1RA, liraglutide (PIONEER 4).


The PIONEER 7 trial assessed the efficacy and safety of oral semaglutide, administered according to an individualized and flexible dose-adjustment approach, compared with a fixed dose of sitagliptin (100 mg) for 52 weeks.

 Rather than the fixed-dose schedule used in the other PIONEER trials (after initial dose escalation), flexible dose adjustment was utilized, designed to mimic the individualized approach used in clinical practice, whereby the dose was increased or decreased depending on the patient’s glycemic response and gastrointestinal tolerability.


Oral semaglutide was also evaluated in specific patient populations. Renal function is a consideration when choosing an additional glucose-lowering treatment. For example, renal excretion of DPP-4is (except linagliptin) necessitates dose adjustment in patients with renal dysfunction.

 In a pharmacokinetic study of oral semaglutide in patients with renal impairment, including end-stage renal disease, no clinically relevant change in semaglutide exposure was observed; therefore, no dose adjustment is recommended.

 The PIONEER 5 trial was conducted to explore the efficacy and safety of oral semaglutide 14 mg versus placebo in patients with T2D and moderate renal impairment (estimated glomerular filtration rate [eGFR], 30-59 mL/min/1.73 m²).17 In this trial, 60% of patients had an eGFR of 45 to less than 60 mL/min/1.73 m² and 40% had an eGFR of 30 to less than 45 mL/min/1.73 m²,

 whereas mean eGFR was at least 95 mL/min/1.73 m² in the PIONEER 1 to 4 and 7 trials,

 Atherosclerotic CVD (coronary heart disease, cerebrovascular disease, or peripheral arterial disease) is the leading cause of morbidity and death in patients with T2D, resulting in an annual cardiovascular (CV)-related expenditure of $37.3 billion associated with diabetes.

 The CV outcomes trial, PIONEER 6, assessed the effects of oral semaglutide versus placebo in patients with T2D at high risk of CV events,


Oral semaglutide was initiated at a dose of 3 mg for all patients, before escalating to 7 mg after 4 weeks, and then to 14 mg after a further 4 weeks depending on the treatment arm.

 Patients were instructed to take oral semaglutide once daily in the morning on an empty stomach, with no more than 4 fl oz (120 mL) water, and to wait 30 minutes before consuming any food, further fluids, or any other oral medication.

 This is because a shorter delay may decrease semaglutide absorption.


The primary and confirmatory secondary end points in most PIONEER trials were change from baseline in A1C level and body weight, respectively, at week 26 (Figure 1

). An exception was PIONEER 7, in which the primary end point was the proportion of patients achieving the ADA-recommended target of an A1C level less than 7.0% (53 mmol/mol) at week 52.

 A1C and body weight outcomes were not evaluated for statistical difference to placebo in PIONEER 6,

How Does the Phase 3a Program of Oral Semaglutide Compare With That of Injectable Semaglutide?


Injectable once-weekly semaglutide was first approved by the FDA in 2017 to improve glycemic control in T2D,

 based on results from the SUSTAIN phase 3a clinical trial program. The global phase 3a program for injectable semaglutide was conducted in 7215 participants across 6 trials: SUSTAIN 1, 4, and 5 for 30 weeks; SUSTAIN 2 and 3 for 56 weeks; and SUSTAIN 6 for 104 weeks.

 Following completion of the SUSTAIN 1 through SUSTAIN 6 trials, results from 4 phase 3b trials with injectable semaglutide (N = 2868; SUSTAIN 7-10) were published.


Across the 6 SUSTAIN phase 3a trials, 2 doses of injectable semaglutide were evaluated (0.5 mg and 1.0 mg), except in SUSTAIN 3, where only semaglutide 1.0 mg was evaluated.

 Once-weekly injectable semaglutide was compared with placebo (SUSTAIN 1, 5, and 6) and the active comparators, sitagliptin (SUSTAIN 2), exenatide extended-release (SUSTAIN 3), and insulin glargine (SUSTAIN 4).


Similar to the PIONEER trials, the primary and confirmatory secondary end points of SUSTAIN 1 through SUSTAIN 5 were change from baseline in A1C level and body weight, respectively; unlike in PIONEER, the main efficacy outcomes were evaluated at the end of treatment (30 or 56 weeks).

 As with PIONEER, there was a dedicated CV outcomes trial, SUSTAIN 6, to assess the effects of injectable semaglutide versus placebo, for 104 weeks, in patients with T2D at high risk of CV events.

Patty Taddei-Allen, PharmD, MBA, BCACP, BCGP

Articles

Hypertrophic Cardiomyopathy Considerations for the Managed Care Pharmacist

The Evidence for Oral Semaglutide in Type 2 Diabetes From a Managed Care Perspective

Efficacy of Oral Semaglutide: Overview of the PIONEER Clinical Trial Program and Implications for Managed Care

Cardiovascular Outcomes, Safety, and Tolerability With Oral Semaglutide: Insights for Managed Care