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Expert Strategies in Heart Failure Care
Expert Strategies in Heart Failure Care: Improving the Utilization of GDMT and SLGT2 Inhibitors to Enhance Patient Outcomes

Released: December 15, 2025

Ty J. Gluckman
Ty J. Gluckman, MD, MHA, FACC, FAHA, FASPC
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Key Takeaways
  • SGLT2 inhibitors are the newest key pillar of GDMT for patients with heart failure regardless of their ejection fraction.
  • Clinical inertia persists as a barrier to GDMT for eligible patients with heart failure; HCPs must overcome this by providing timely and quick titration of GDMT to their target dose.
  • As novel mechanisms of action are discovered and evaluated in patients with heart failure, future therapies will “add to” current guideline recommendations rather than “replace” them.  

In this commentary, Ty J. Gluckman, MD, MHA, answers questions posed by healthcare professionals (HCPs) during a live symposium titled “Arm-in-Arm With Heart Failure Experts: A Master Class in Optimizing Heart Failure Treatment With SGLT2 Inhibitors.” Learn how to improve the delivery of guideline-directed medal therapy (GDMT) for patients with heart failure (HF) across the ejection fraction spectrum, including key considerations for using SGLT2 inhibitors, and what lies ahead in the future of HF care. 

Which new or emerging therapies for HF show the most promise?
For more than 35 years, accumulated clinical trial evidence has led to what we currently recommend as GDMT or the core pillars of therapy in HF. For patients with heart failure with reduced ejection fraction (HFrEF)—defined as a left ventricular ejection fraction of 40% or less—this consists of an angiotensin converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), or angiotensin receptor neprilysin inhibitor (ARNI), an evidence-based beta blocker, a mineralocorticoid receptor antagonist (MRA), and a sodium-glucose cotransporter 2 (SGLT2) inhibitor, along with a loop diuretic in those with symptoms or signs of volume overload. 

For those patients with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF)—defined as an ejection fraction of 41%-49% or >50%, respectively—many of these same therapies are helpful.  Beyond a loop diuretic for those with symptoms or signs of volume overload, SGTL2 inhibitors likely represent the next most important treatment option for this population. Guideline recommendations also exist for an ARB, ARNI, and MRA in this population.

More recently, additional therapies have been shown to provide benefit in patients with HFmrEF and HFpEF. The nonsteroidal MRA finerenone was evaluated in the FINEARTS-HF trial and significantly reduced the risk of cardiovascular death or worsening HF events in this population. In addition, both the GLP-1 receptor agonist semaglutide and the GLP-1/GIP receptor agonist tirzepatide have been shown to be effective in patients with obesity and HFmrEF or HFpEF. Whereas semaglutide improved functional status in patients with HF with and without diabetes in the STEP-HFpEF DM and STEP-HFpEF trials, respectively, tirzepatide improved functional status as well as a composite of cardiovascular death and worsening HF events in the SUMMIT trial.

Finally, new therapeutic targets are also being evaluated in HF. For example, based on longstanding recognition that HF has been associated with systemic inflammation, anti-inflammatory therapies (namely IL-6 inhibitors) are being evaluated as adjunctive therapy to improve hard outcomes in patients with HFmrEF and HFpEF. 

What are the challenges of integrating some of these new therapies into routine HF care?
Given the different but complementary therapies available for use in HF, there is an urgent need to address their significant underutilization, both in terms of use alone and use at target doses shown to be effective. In addition, there is now growing recognition that timely implementation makes a difference. In the STRONG-HF trial, patients with HFrEF randomized to rapid initiation of GDMT (with titration to target doses where appropriate) vs usual care led to significant and meaningful improvement in hard outcomes. Although not specifically studied in HFmrEF or HFpEF, it is important to recognize that timely initiation of multiple therapies in HF helps keep patients alive and out of the hospital.

Another big change in practice involves finding ways to ensure that patients hospitalized with HF receive effective therapies. Starting GDMT during a patient’s hospitalization increases the likelihood that they will continue their treatment post discharge—a key driver of long-term treatment adherence.

I’d be remiss if I didn’t acknowledge that challenges exist. Polypharmacy, affordability, and tolerability can be barriers to adoption of GDMT. However, we less often talk about the risks of omitting GDMT. Of importance, these include an increased risk of death and hospitalization. 

Are there specific patient subgroups for whom these new HF treatments are particularly beneficial or less effective?
Patients with or at risk for HF should be classified further to help determine the best treatment approach. This generally includes a patient’s HF stage, type, and class.

There are 4 stages of HF: A, B, C, and D. Patients with stage A HF have risk factors that increase the possibility of HF (eg, hypertension, diabetes, obesity), but they lack symptoms/signs of HF, structural/functional abnormalities, and elevated cardiac biomarkers. Patients with stage B HF lack symptoms/signs of HF, but have structural abnormalities, elevated filling pressures, and/or elevated cardiac biomarkers that predate overt HF.  Patients with stage C HF—the condition that we usually talk most about—have current (or previous) symptoms/signs of HF. Finally, patients with stage D or advanced HF have pronounced symptoms/signs that significantly interfere with daily life.

HF type is defined by a patient’s left ventricular ejection fraction (LVEF). This includes HFrEF (LVEF ≤40%, HFmrEF (LVEF 41%-49%), and HFpEF (LVEF ≥50%). Because a patient’s LVEF can change, it’s important to reclassify a patient’s HF type following reassessment of left ventricular systolic function.

Finally, a patient’s functional class (most often assessed using the New York Heart Association classification on a scale of I to IV) provides insights about how limited a patient is by activity.

To date, studies have disproportionately enrolled patients with stage C HF and NYHA class 2 or 3 functional status. Most often, studies have also evaluated patients with HFrEF separately from those with HFmrEF or HFpEF. Finally, certain clinical criteria (eg, renal function, natriuretic peptide levels) have been used to either exclude or enrich patient’s participation. For all these reasons, it is important to know who was included in a clinical trial to help determine which patient populations are most likely to benefit from its use. 

Are there best practices for monitoring potential toxicities or the long-term risks associated with newer HF therapies?
Patients with HF may be monitored in different ways. To assess for toxicity, routine assessment of electrolytes and renal function (eg, for MRAs), and even drug levels (eg, for digoxin) is important. Significant opportunity exists, however, in further personalizing HF therapies based on efficacy, safety, and tolerability.

How do you see the standard of care for HF evolving over the next few years?
I think novel mechanisms of action will continue to be tested to determine if they meaningfully improve the hardest outcomes (eg, cardiovascular mortality, hospitalization for HF). Of note, guidance has been previously provided about ways that new therapies may be approved based on their ability to improve symptoms or functional status alone (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/treatment-heart-failure-endpoints-drug-development-guidance-industry).

Most HF care is based on a world where drug therapy is an “add to” rather than “replacement of.” For new therapies with different and/or complementary mechanisms of action, they are usually added to those receiving standard of care. At odds with this are the challenges of polypharmacy—where patients with HF may be prescribed 4 or more treatments for HF alone—and potential effects on adherence.

How do SGLT1 inhibitors affect wound healing? Should HCPs be concerned about this?
There is a single FDA-approved dual SGLT1/2 inhibitor that was developed initially to also improve glycemic control in patients with diabetes by modulating glucose absorption in the small intestine. That drug, sotagliflozin, has now been studied in patients with HF and type 2 diabetes, and was shown to improve HF outcomes across a wide range of LVEFs. It has been incorporated into the HF guidelines similar to other SGLT2 inhibitors.

There are data suggesting that antagonizing the SGLT 1 and/or 2 receptors can have immunomodulatory anti-inflammatory effects. At this time, however, such therapies have not been approved to promote wound healing.

Although SGLT1/2 and SGLT2 inhibitors have been studied in type 1 diabetes, they are not approved for patients with this condition and increase the risk of diabetic ketoacidosis. 

Are there GDMT utilization registries for the outpatient setting?
Although HF registries have contributed significantly to our understanding of ongoing care gaps, they have largely studied inpatient care.  Nonetheless, they have consistently demonstrated underuse of GDMT across the LVEF continuum, with numerous opportunities for care improvement.

Claims-based studies have disproportionately extended our understanding about care gaps to the outpatient setting. Although not without limitations, findings from these analyses nonetheless highlight ongoing shortcomings in getting patients on wide-ranging effective therapies.

Your Thoughts
When managing patients with HF, how often do you include SGLT2 inhibitors in their treatment plan? You can get involved in the discussion by answering the poll question and posting a comment below.

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When managing patients with HF, how often do you include SGLT2 inhibitors in their treatment plan?

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