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SGLT2 Inhibitors in HF
Key Takeaways and Expert Answers: SGLT2 Inhibitors in Heart Failure Management

Released: December 10, 2024

Expiration: December 09, 2025

Javed Butler
Javed Butler, MD, MPH, MBA
Ty J. Gluckman
Ty J. Gluckman, MD, MHA
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Key Takeaways
  • SGLT2 inhibitors represent a safe, well-tolerated, and effective therapy for heart failure across the spectrum of left ventricular ejection fraction, with added renal protection and minimal impact on blood pressure.
  • Supported by strong clinical trial evidence, healthcare professionals should prioritize SGLT2 inhibitors in patients with heart failure; alternative options may be considered when insurance coverage or cost pose a limiting barrier. 

SGLT2 Inhibitors: The Ideal Heart Failure Therapy
Sodium-glucose cotransporter-2 (SGLT2) inhibitors represent an excellent treatment option for patients with heart failure across the entire spectrum of left ventricular ejection fractions. It is a once-daily oral medication, and patients usually express a preference for this therapy because it provides consistent effects throughout the day.

SGLT2 inhibitors help patients with heart failure live longer, feel better, and avoid hospitalization. This class of medication has been demonstrated to be safe and well tolerated, while offering renal protection with a minimal effect on blood pressure. It is usually affordable but may require utilization of pharmacy assistance programs to make it accessible. Ensuring that patients receive guideline-recommended treatment to derive the benefits observed in clinical trials is a particularly rewarding aspect for all of us that care for these patients.

US Guideline vs EU Guideline Differences for SGLT2 Inhibitors
Despite their shared mechanism of action, there are molecular differences between the SGLT2 inhibitors. In the European heart failure guidelines, specific SGLT2 inhibitors are called out by clinical trial evidence, including dapagliflozin, empagliflozin and sotagliflozin. In contrast, the US heart failure guidelines consider the benefits derived from SGLT2 inhibitors as a class effect. Recognizing that this latter approach may be simpler and affords greater flexibility in prescribing, it may also oversimplify things.

It is misleading to assume that all drugs within a class have the same efficacy and safety. For example, favorable cardiovascular outcomes have been observed with the β-blockers bisoprolol, carvedilol, and metoprolol succinate, but not with bucindolol and nebivolol in patients with heart failure with reduced ejection fraction (HFrEF). Similarly, among the dipeptidyl peptidase-4 inhibitors, a drug class used to improve glycemic control in diabetes, alogliptin and saxagliptin have been associated with worsened heart failure outcomes, whereas linagliptin and sitagliptin have not. These examples highlight the importance of using clinical trial data for specific medications to inform one’s treatment approach. 

Wherever possible, it is preferable to prioritize SGLT2 inhibitors with proven clinical evidence. In circumstances where such therapies are unavailable and/or unaffordable, use of an alternative SGLT2 inhibitor is better than avoidance of the drug class altogether.

Strategies for Managing the Cost of SGLT2 Inhibitors
Addressing the out-of-pocket cost of SGLT2 inhibitors for patients with heart failure may require exploring one or more approaches. For starters, it is worth comparing the cost of dapagliflozin, empagliflozin, and sotagliflozin, and how this compares with other alternatives within the class, including bexagliflozin, canagliflozin, and ertugliflozin.

Patient assistance programs represent another valuable resource to help manage medication costs. Patients with commercial insurance can often obtain $0 (or low cost) copay/discount cards; those on Medicaid coverage usually have a straightforward prior authorization process; and those without insurance usually qualify for a patient assistance program. In contrast, patients insured under Medicare Part D can present greater challenges and often require creative solutions. While it may seem counterintuitive, uninsured patients and those covered by Medicaid often experience fewer barriers and better access to coverage compared to those insured under Medicare.  

Managing Recurrent Genitourinary Infections With SGLT2 Inhibitors  
Based on available evidence, a patient’s risk of genitourinary infections appears consistent across the SGLT2 inhibitor drug class. As such, switching agents is unlikely to significantly reduce this risk. Instead, the focus should be on educating patients about hygiene practices that have been shown to be effective at preventing infections. For individuals experiencing recurrent or complicated infections, consulting an infectious disease specialist may also be beneficial.  

Hyponatremia and Considerations for Therapy
Hyponatremia is a marker of poor prognosis in heart failure. SGLT2 inhibitors promote natriuresis through sodium–hydrogen exchange pumps in the kidneys along with osmotic diuresis from glucose-related fluid loss. Collectively, these mechanisms result in greater loss of free water compared to sodium excretion, with the potential to improve hyponatremia rather than worsen it. Therefore, hyponatremia should not be considered a contraindication to the use of SGLT2 inhibitors in appropriate clinical situations.  

Combination Therapy With GLP-1 Receptor Agonists in HFpEF Management
Recent studies have demonstrated benefit with the use of glucagon-like peptide-1 (GLP-1) receptor agonists and Gastric inhibitory polypeptide (GIP)/GLP-1 coagonists in patients with obesity and heart failure with preserved ejection fraction (HFpEF). Importantly, this evolution in heart failure management parallels earlier breakthroughs. For example, in the early 1990s, angiotensin-converting enzyme inhibitors transformed the treatment of HFrEF. And much more recently, SGLT2 inhibitors transformed the treatment of patients with HFrEF, heart failure with mildly reduced ejection fraction (HFmrEF), and HFpEF.  

Acknowledging that while GLP-1 receptor agonists and GIP/GLP-1 coagonists will not replace SGLT2 inhibitors, they are likely to end up as a complementary therapy, at least in patients with obesity and HFpEF. Such an approach expands the treatment options for these patients in meaningful ways.  

Your Thoughts?
What strategies do you most often use to make sure your patients are able to afford their SGLT2 inhibitors? Get involved in the discussion by posting a comment below!  

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What strategies have you used most often to help make SGLT2 inhibitors more affordable for your patients with heart failure?

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