Skip to content
Welcome to Heart Matters - Empowering Heart Health
Research Insights

Promising Research on SGLT2 Inhibitors for Heart Failure Treatment

Heart failure is a debilitating condition that affects millions of people worldwide. However, recent research has shed light on a potential breakthrough in heart failure treatment using a class of drugs called SGLT2 inhibitors. This article will explore the latest research on SGLT2 inhibitors for heart failure and discuss their promising benefits.

 

Quick Dive into Heart Failure: Understanding the Basics

Heart failure, a common condition, happens when the heart can’t effectively pump blood, leading to oxygen and nutrient shortage in tissues. It results from factors like coronary disease, high blood pressure, or previous heart attacks.

As it worsens, the heart’s pumping efficiency drops, causing symptoms like breathlessness, fatigue, leg swelling, and reduced exercise tolerance. Based on pumping and filling issues, it’s classified into systolic and diastolic types. Detecting it early, lifestyle changes and proper medical treatments are vital for managing and improving life quality, possibly slowing progression.

 

YouTube player

 

 

What are SGLT2 Inhibitors?

SGLT2 (sodium-glucose cotransporter 2) inhibitors are a type of medication commonly used to manage type 2 diabetes. These drugs work by blocking the action of SGLT2, a protein found in the kidneys that reabsorbs glucose back into the bloodstream. By inhibiting SGLT2, these medications increase the excretion of glucose through urine, lowering blood glucose levels in people with diabetes.

 

New Research on SGLT2 Inhibitors and Heart Failure

In recent years, several large clinical trials have investigated the use of SGLT2 inhibitors in patients with heart failure, both with and without diabetes. The results have been groundbreaking, showing significant benefits in improving heart failure outcomes. Here are some key findings from the research:

Reduction in Hospitalization for Heart Failure:

Studies such as the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial and the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) trial have shown that SGLT2 inhibitors can reduce the risk of hospitalization for heart failure by up to 30% in patients with heart failure, regardless of their diabetes status[1-2].

Lowering of Cardiovascular Mortality:

SGLT2 inhibitors have demonstrated the ability to lower the likelihood of cardiovascular mortality among individuals with heart failure. To recap, heart failure is characterized by a weakened heart muscle that compromises its capacity to circulate blood throughout the body efficiently.

The EMPEROR-Reduced and EMPEROR-Preserved trials, which specifically studied the use of empagliflozin in heart failure patients, demonstrated a significant reduction in cardiovascular death and heart failure-related hospitalization[3-4].

Improvement in Quality of Life:

SGLT2 inhibitors have been shown to improve symptoms and quality of life in patients with heart failure. Patients treated with SGLT2 inhibitors have reported fewer symptoms such as shortness of breath, fatigue, and fluid retention, leading to an improved quality of life and functional status[5].

Favorable Effects on Cardiac Remodeling:

Research has also shown that SGLT2 inhibitors may benefit cardiac remodeling and the structural and functional changes in the heart during heart failure. These drugs have been shown to reduce markers of cardiac stress and inflammation and improve cardiac function and remodeling in heart failure patients[6-7].

Potential kidney Benefits:

SGLT2 inhibitors may also have potential renal benefits in patients with heart failure. These medications have been shown to reduce the risk of kidney dysfunction and progression of kidney disease in heart failure patients, which is an important comorbidity often associated with heart failure[8-10].

 

Implications for Clinical Practice

Recent research offers promising insights into SGLT2 inhibitors for heart failure, with potential clinical implications. These findings suggest that SGLT2 inhibitors could enhance heart failure treatment options, regardless of diabetes status. They might complement standard therapies like ACE inhibitors, beta-blockers, and diuretics.

SGLT2 inhibitors are currently recommended for heart failure patients with reduced ejection fraction, a measure of heart pumping efficiency. Recently, they have also shown promise for patients whose heart function is normal.

Collaboration with healthcare providers is essential to tailor treatment plans. Dosage, timing, and interactions with other medications require careful customization based on individual needs.

 

If you have been diagnosed with heart failure, it is worthwhile asking your healthcare professional about whether there is a role for SGLT2 inhibitors to help your condition.

 

Advantages for Patients with and without Diabetes

What sets SGLT2 inhibitors apart is their capacity to act independently of diabetes. This means that even individuals without diabetes who are grappling with heart failure can reap the benefits of these inhibitors. The independence of their efficacy from diabetes ushers in a new era of personalized medicine, where treatments can be tailored to address specific medical conditions rather than being confined to traditional disease categories.

 

Side Effects and Precautions

SGLT2 inhibitors offer advantages, but potential side effects need consideration. A prominent effect is increased UTI risk due to higher urine glucose. Genital fungal infections can also occur because the glucose content fosters growth.

Dehydration and low blood pressure are notable concerns. These inhibitors boost urine glucose excretion, leading to more urination and potential fluid loss. This can lower blood pressure, causing dizziness or fainting when standing quickly.

Ketoacidosis risk is linked, although rare. Vigilance for ketoacidosis signs—nausea, vomiting, abdominal pain, confusion—is crucial.

Attention is necessary if taking kidney-affecting medications, as SGLT2 inhibitors operate directly on the kidneys. Adjustments might be needed for optimal kidney health.

While potential effects don’t diminish benefits, they emphasize informed medical management. Before treatment, comprehensive discussions on medical history, health status, and risks are vital. Monitoring and communication ensure a positive treatment experience while minimizing drawbacks.

 

Dosing Guidelines

The dosing of SGLT2 inhibitors can vary depending on the specific inhibitor and the individual’s medical condition. Typically, these medications are taken orally, and depending on the formulation, the dosing frequency can range from once daily to once weekly.

Global Variations in Generic and Trade Names:

Various generic and trade names across the world know SGLT2 inhibitors. For instance, the generic name “empagliflozin” can be found under trade names like “Jardiance” in the United States, “Jardiamet” in Europe, and “Glyxambi” in some regions. Similarly, “dapagliflozin” is recognized as “Farxiga” in the U.S., “Forxiga” in Europe, and “Xigduo” when combined with metformin. “Canagliflozin” is referred to as “Invokana” in the U.S. “Invokamet” when combined with metformin. Awareness of these variations is crucial to ensure accurate communication between healthcare professionals and patients.

 

Conclusion

Recent research on SGLT2 inhibitors for heart failure brings exciting breakthroughs. These medications offer significant benefits like reduced hospitalization, better cardiovascular outcomes, improved life quality, and potential impacts on cardiac remodeling and renal function. Initially designed for diabetes, SGLT2 inhibitors are gaining recognition as game-changers in heart failure treatment.

Remembering SGLT2 inhibitors should only be used under a qualified healthcare professional’s guidance is vital. Patients mustn’t alter medications without consulting their doctor. Ongoing research aims to grasp long-term effects and safety across different groups.

 

References:

  1. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008.
  2. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-2128.
  3. Packer M, Anker SD, Butler J, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020;383(15):1413-1424.
  4. Packer M, Anker SD, Butler J, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021;385(16):1451-1461.
  5. Fitchett D, Inzucchi SE, Lachin JM, et al. Long-term Heart Failure Outcomes in Patients With Type 2 Diabetes Mellitus Treated With Empagliflozin Versus Placebo in EMPA-REG OUTCOME. Circulation. 2021;143(3):249-261.
  6. Verma S, McMurray JJV. SGLT2 inhibitors and mechanisms of cardiovascular benefit: A state-of-the-art review. Diabetologia. 2018;61(10):2108-2117.
  7. Byrne NJ, Matsumura N, Maayah ZH, et al. Empagliflozin prevents worsening of cardiac function in an experimental model of pressure overload-induced heart failure. Cardiovasc Diabetol. 2017;16(1):9.
  8. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019;380(24):2295-2306.
  9. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383(15):1436-1446.
  10. FDA approves new treatment for heart failure. U.S. Food and Drug Administration. Accessed March 15, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-heart-failure
About the author

Heart Matters, edited by cardiologist Professor Peter Barlis, is a trusted resource that offers clear and accurate information on cardiovascular health. It bridges the gap between scientific research and everyday understanding, empowering you to make informed choices and take an active role in supporting your heart health.

Our Youtube Channel

Discover our Heart Matters YouTube channel, where we bring heart health to life. From explaining common conditions and symptoms to discussing the latest research, our engaging videos simplify complex topics, ensuring you have access to valuable knowledge for a healthier heart. Subscribe now and embark on a journey of education, empowerment, and inspiration.

Editor's Picks

informing hearts
empowering lives

Subscribe to our newsletter and be the first to receive valuable insights, tips, and resources on heart health.

other anti-anginals

When first-line therapies for angina, such as beta blockers, calcium channel blockers, and nitrates, prove inadequate or are not well-tolerated, second-line therapies may be considered.
Perhexiline is a unique medication that enhances the heart's ability to utilize fatty acids for energy, reducing its reliance on oxygen and lowering oxygen demand. This action helps improve blood flow and alleviates chest pain in some patients with refractory angina.
Nicorandil is another second-line option with a dual mechanism of action. It opens potassium channels in smooth muscle cells, causing vasodilation and enhancing coronary blood flow. Additionally, nicorandil also stimulates nitric oxide release, further dilating blood vessels and reducing heart workload.
Trimetazidine is an anti-ischemic agent that improves cardiac efficiency by enhancing glucose metabolism and shifting the heart's energy production to a more oxygen-efficient process. As second-line therapies, these medications offer alternative approaches for managing angina in individuals who do not respond adequately to first-line treatments or those experiencing side effects from other medications.

lipid lowering therapies

Lipid-lowering therapies are essential in managing coronary artery disease (CAD), a condition where the arteries supplying blood to the heart become narrowed. Among the most commonly prescribed treatments are statins, which reduce cholesterol production in the liver and significantly lower the risk of heart attacks and strokes.

Other medications may be used to target different aspects of lipid metabolism:

  • Ezetimibe helps reduce the absorption of cholesterol in the gut
  • Fibrates lower triglyceride levels
  • Niacin can help raise high-density lipoprotein (HDL) cholesterol

In recent years, a newer class of medications known as PCSK9 inhibitors—such as Repatha (evolocumab)—has become available. These drugs block a specific enzyme involved in cholesterol regulation and can dramatically lower LDL cholesterol, particularly in patients who do not achieve target levels with statins alone.

Together, these therapies provide a range of options to personalise treatment and improve cardiovascular outcomes.

Nitrates

Nitrates for Angina Relief

Nitrates are widely used to treat angina and provide quick relief from chest pain. These medications are commonly available as sublingual sprays or tablets, skin patches, and long-acting tablets.

Nitrates work by dilating blood vessels, allowing for increased blood flow and reduced vascular resistance. This reduces the heart’s workload and lowers its oxygen demand, offering prompt relief from angina symptoms.

Sublingual nitrates act quickly and are typically used at the onset of angina symptoms, while patches and long-acting tablets are used for ongoing prevention.

Common side effects include headaches, dizziness, and flushing. These often improve with continued use but should be discussed with a healthcare provider if persistent or bothersome.

calcium channel blockers

Calcium channel blockers, including amlodipine, felodipine, Cardizem (diltiazem), and verapamil, are commonly prescribed for the treatment of angina.

These medications work by inhibiting the influx of calcium into the muscle cells of the heart and blood vessels, causing them to relax. This relaxation leads to the widening of blood vessels, which improves blood flow and reduces blood pressure.

For individuals with angina, calcium channel blockers reduce the heart’s workload and oxygen demand, helping to relieve chest pain and prevent angina episodes.

While effective, they may cause side effects such as headaches, dizziness, facial flushing, and ankle swelling. These effects should be monitored and discussed with your healthcare provider if they persist.

Beta blockers

Beta blockers, such as metoprolol, propranolol, atenolol, carvedilol, and bisoprolol, play a crucial role in managing angina.

These medications work by blocking specific receptors in the heart, which slows the heart rate and reduces the strength of each contraction. This results in a lower oxygen demand by the heart and helps relieve chest pain associated with angina.

Beta blockers are highly effective in both relieving symptoms and preventing angina episodes. However, they may cause side effects in some individuals, including tiredness, worsened asthma symptoms, more vivid dreams, and erectile dysfunction in some males.

It is important to consult your healthcare provider to determine whether beta blockers are a suitable option for your angina and overall heart health.

Anti-platelet Medications

Anti-platelet medications play a crucial role in preventing blood clot formation and reducing the risk of serious cardiovascular events such as heart attacks and strokes. Commonly used agents include aspirin, clopidogrel, and ticagrelor.

 

Aspirin: This well-known medication inhibits platelet activation, reducing the likelihood that platelets will clump together and form clots. It is widely used for both primary and secondary prevention of heart attacks and strokes.

 

Clopidogrel: A potent anti-platelet agent, clopidogrel works by blocking specific receptors on platelets to prevent aggregation. It is commonly prescribed for patients with acute coronary syndrome, those undergoing stent placement, and some individuals with peripheral arterial disease.

 

Ticagrelor: Ticagrelor also inhibits platelet activation and is typically used in the treatment of acute coronary syndrome. It is often prescribed alongside aspirin to provide dual anti-platelet therapy and further reduce the risk of heart-related events.