Do SGLT2 Inhibitors Treat Heart Failure Without Diabetes?

Yes. SGLT2 inhibitors—such as dapagliflozin and empagliflozin—are an important guideline-recommended treatment for many people with heart failure, even if they do not have diabetes.

While originally developed to lower blood sugar in people with type 2 diabetes, large clinical trials discovered that they provide major benefits for the heart and kidneys regardless of a person’s diabetes status ^[1][2]. They work by blocking the kidneys from reabsorbing glucose and sodium, which has osmotic and diuretic effects that help lower pressure inside the heart and blood vessels ^[3]. Because they do not force the body to release extra insulin, the risk of dangerously low blood sugar (hypoglycemia) is very uncommon when these medications are used alone in people without diabetes ^[4]. Today, they are considered a core addition to standard heart failure therapies ^[5].

What This Medicine Is—And Is Not

• It is not a diabetes diagnosis or a cure for heart failure.
• It is intended to be taken alongside your other prescribed heart failure medications ^[5].
• It generally does not require you to check your blood sugar at home unless your clinician specifically tells you to.

How SGLT2 Inhibitors Help Your Heart

The exact benefits you might experience depend slightly on your specific type of heart failure. Heart failure is often categorized by ejection fraction (the percentage of blood your heart pumps out with each beat):

• Reduced Ejection Fraction (HFrEF, 40% or less): For people with HFrEF, SGLT2 inhibitors significantly reduce the combined risk of worsening heart failure and cardiovascular death ^[1][2]. The most consistent effect is a major reduction in heart failure hospitalizations ^[1]. In pooled analyses of trials, they have also been shown to lower the risk of cardiovascular and all-cause death in this specific group ^[6].
• Mildly Reduced (HFmrEF, 41–49%) and Preserved Ejection Fraction (HFpEF, 50% or more): For those with higher ejection fractions, these medications significantly lower the combined risk of worsening heart failure and cardiovascular death, driven primarily by preventing heart failure hospitalizations ^[7][8]. While they have not been proven to independently lower the risk of death in these groups ^[9], keeping patients out of the hospital is an important benefit.

Across all types of heart failure, patients taking SGLT2 inhibitors may experience better physical function, improved health-related quality of life, and fewer daily heart failure symptoms ^[10].

What to Expect: Kidney Numbers and Fluid Balance

When you start taking an SGLT2 inhibitor, your care team will assess your bloodwork, blood pressure, and volume status.

• The “eGFR Dip”: You may see an early, mild drop in your eGFR (a laboratory measure of kidney function) ^[11][12]. This is usually an expected functional change in pressure inside the kidneys rather than true kidney damage, and it ultimately helps protect your kidneys from long-term decline ^[11][4]. However, a large or persistent drop should be evaluated by your clinician ^[13]. Do not ignore signs of poor kidney function or stop the medication on your own.
• Fluid Volume and Blood Pressure: Because these drugs cause you to excrete more sodium and fluid in your urine, they can lower your blood pressure slightly ^[3][14]. Continue to follow your individualized fluid plan—do not drink extra fluids without asking your doctor. Because of this fluid loss, your doctor might need to adjust your other diuretic (water pill) doses to prevent dehydration ^[14]. Watch for signs of volume depletion, such as marked dizziness on standing, fainting, unusual weakness, or a severe decrease in urine output, and contact your doctor if these occur ^[3][15]. Never change your water pill dose yourself.

Important Risks and “Sick Day” Rules

While generally well-tolerated, SGLT2 inhibitors carry specific risks requiring your attention:

• Genital Infections: These medications increase the risk of genital yeast (fungal) infections ^[16][17]. These are usually mild and treatable. While ordinary urinary tract infections are not consistently increased for everyone, a very rare but severe infection of the perineum (the area between the genitals and anus) can occur ^[18][17].
• Rare Ketoacidosis: A rare but dangerous build-up of acids in the blood called ketoacidosis can occur, even in people without diabetes ^[18][19]. Importantly, this can happen even if your blood sugar levels are completely normal ^[18]. Ketoacidosis is often triggered by severe physical stress, such as fasting, vomiting, ketogenic diets, or heavy alcohol use ^[19][20].
• Surgery and Illness Rules: To prevent ketoacidosis, you must follow strict “sick day” rules: contact your doctor to temporarily pause this medication during severe illness, persistent vomiting or diarrhea, severe dehydration, or prolonged fasting ^[19][21]. Additionally, these medications are typically stopped at least 3 days before any scheduled surgery or procedure requiring fasting (always confirm the exact timeline with your surgical team) ^[19][21]. They should generally only be restarted when you are clinically stable and eating and drinking normally.

When to Get Emergency Help

Seek urgent medical care and tell clinicians you are taking an SGLT2 inhibitor if you experience:

• Signs of Ketoacidosis: Nausea, persistent vomiting, unusual stomach pain, rapid or deep breathing, severe weakness, or confusion ^[19][20]. Do not wait for a high blood sugar reading.
• Signs of a Severe Perineal Infection: Rapidly worsening pain, redness, or swelling in the area between the genitals and anus, especially with a fever or feeling very unwell ^[18].
• Signs of Severe Dehydration: Fainting, marked dizziness, or a sudden, severe drop in urine output ^[3].