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SGLT2 Inhibitors: How These Medications Are Transforming Heart Failure Care: For Diabetics and Non-Diabetics Alike

It’s not often that a class of medication reshapes how we manage both heart failure and diabetes, but SGLT2 inhibitors have done exactly that. Originally developed to lower blood sugar in people with type 2 diabetes, these drugs have demonstrated remarkable benefits in individuals with heart failure, including those without diabetes.

In my clinical practice, I’ve seen how SGLT2 inhibitors can improve breathlessness, reduce fluid overload, and lead to meaningful weight loss. Their benefits go far beyond glucose control and have proven transformative for many people living with heart failure. Let’s explore these agents a little further.

 

What Are SGLT2 Inhibitors?

SGLT2 inhibitors (sodium-glucose co-transporter 2 inhibitors) – such as dapagliflozin, empagliflozin, and canagliflozin – work by promoting the excretion of excess glucose through the urine. In doing so, they also produce a mild diuretic effect, lower blood pressure, and support modest weight loss. But it is their impact on heart failure that has generated the most attention in recent years.

 

A New Standard in Heart Failure – HFrEF and HFpEF

Heart failure is generally classified into two types:

  1. HFrEF (heart failure with reduced ejection fraction), where the heart’s ability to pump is weakened
  2. HFpEF (heart failure with preserved ejection fraction), where the heart’s relaxation is impaired despite a normal pumping function

SGLT2 inhibitors are one of the few therapies shown to be effective in both types of heart failure – regardless of whether diabetes is present.

 

In HFrEF (Reduced Ejection Fraction):

Clinical trials such as DAPA-HF and EMPEROR-Reduced have shown that SGLT2 inhibitors:

  • Reduce the risk of hospitalisation for heart failure
  • Improve symptoms such as fatigue and breathlessness
  • Lower the risk of cardiovascular death
    These benefits were seen consistently in patients with and without diabetes.

 

In HFpEF (Preserved Ejection Fraction):

HFpEF has historically been challenging to treat. However, large studies like EMPEROR-Preserved and DELIVER have demonstrated that SGLT2 inhibitors:

  • Reduce the risk of hospitalisation
  • Improve exercise capacity and quality of life
  • Provide symptomatic relief for patients regardless of diabetic status

 

Guidelines now recommend SGLT2 inhibitors for all patients with heart failure, not just those with diabetes.

 

Relieving Shortness of Breath and Fluid Retention

Shortness of breath is one of the most common and distressing symptoms of heart failure. SGLT2 inhibitors have a mild but effective diuretic-like effect, which helps the body eliminate excess fluid while maintaining electrolyte balance.

Patients often experience:

  • Reduced swelling in the legs and ankles
  • Less breathlessness when lying flat
  • Improved energy levels and ability to perform daily activities
  • Fewer hospital admissions related to fluid overload
  • Unlike traditional diuretics, SGLT2 inhibitors don’t typically cause large volume shifts or potassium loss, making them easier to tolerate.

 

Additional Benefits Beyond the Heart

1. Weight Loss and Reduced Appetite
Most people taking SGLT2 inhibitors experience a modest but sustained weight loss – typically between 2 and 4 kilograms. Many also report a natural reduction in appetite, which supports longer-term lifestyle changes and improved metabolic health.

2. Kidney Protection
SGLT2 inhibitors reduce pressure within the kidneys and help slow the progression of chronic kidney disease (CKD). They are now considered part of standard treatment for individuals with CKD, whether or not they have diabetes.

3. Lowering Blood Pressure
By encouraging sodium and water excretion, SGLT2 inhibitors contribute to a modest reduction in blood pressure – without significantly affecting heart rate or causing low blood pressure in most people.

 

Transformative in Clinical Practice

In day-to-day care, the impact of SGLT2 inhibitors can be dramatic. Many patients notice improvements in symptoms within weeks:

  • Easier breathing
  • Better exercise tolerance
  • Fewer admissions to hospital
  • Enhanced overall wellbeing
  • In my experience, SGLT2 inhibitors have changed the trajectory of care for many individuals with heart failure. They are not only well tolerated, but often life-enhancing.

 

Who Should Consider an SGLT2 Inhibitor?

SGLT2 inhibitors are now recommended for:

  • Individuals with heart failure (HFrEF or HFpEF)
  • People with type 2 diabetes and cardiovascular disease
  • Those with chronic kidney disease, including people with proteinuria (loss of protein from the kidneys into the urine)

These medications are generally well tolerated, though potential side effects include urinary tract infections and, in rare cases, diabetic ketoacidosis (mainly in insulin-dependent diabetes). Your doctor will consider these factors when prescribing.

 

Conclusion

SGLT2 inhibitors have moved beyond their origins in diabetes management to become essential tools in the treatment of heart failure. For people with HFrEF or HFpEF, and those living with chronic kidney disease or type 2 diabetes, these medications offer significant clinical benefits and symptom relief. Their ability to reduce hospitalisations, relieve breathlessness, promote weight loss, and improve quality of life makes them a cornerstone of modern cardiovascular care.

About the author
Cardiologist & Founding Editor

Peter is an interventional cardiologist and the Founding Editor of Heart Matters, a trusted resource for heart health education. With more than 20 years of clinical experience, he is dedicated to making cardiovascular care more understandable and accessible. His work bridges patient care, research, and public education, empowering individuals to take control of their heart health. Professor Barlis is internationally recognised for his contributions to cardiology, with numerous publications and speaking engagements around the world.

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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.