Jardiance (empagliflozin) helps the heart by reducing the workload on it through several overlapping mechanisms, including flushing excess sodium and fluid from the body, lowering blood pressure, and improving the heart muscle’s ability to contract. Originally developed as a diabetes medication, it is now FDA-approved for heart failure regardless of whether someone has diabetes. In major clinical trials, it cut the combined risk of cardiovascular death or heart failure hospitalization by roughly 34% compared to placebo.
How Jardiance Reduces Strain on the Heart
Jardiance belongs to a class of drugs called SGLT2 inhibitors. These work primarily in the kidneys, where they block a protein responsible for reabsorbing sugar and sodium back into the bloodstream. By blocking that protein, the drug causes your body to excrete more glucose and sodium in the urine. That extra sodium pulls water along with it, producing a mild diuretic effect.
This matters for the heart because excess fluid in the body directly increases how hard the heart has to pump. Reducing that fluid volume lowers two critical forces the heart works against: preload (the volume of blood filling the heart before each beat) and afterload (the resistance the heart pumps against when pushing blood out). Lowering both simultaneously takes meaningful pressure off a struggling heart, and this effect kicks in relatively quickly, within days to weeks of starting the medication.
Blood pressure also drops modestly as fluid volume decreases. But the benefits go beyond simple fluid removal. In animal studies of heart failure, empagliflozin improved the heart muscle’s intrinsic ability to contract, measured independently of how much blood was filling the heart or how much resistance it faced. Rats with heart damage that received empagliflozin showed significantly stronger cardiac contractility and actually had higher systolic blood pressure (132 vs. 120 mmHg) than untreated rats with the same damage, suggesting the heart was pumping more effectively rather than just working under less strain.
The Kidney Connection
The heart and kidneys are deeply intertwined. When one starts to fail, the other typically follows. Jardiance interrupts this cycle at the kidney level by restoring a feedback system called tubuloglomerular feedback, which normally regulates pressure inside the kidney’s filtering units. In conditions like diabetes and heart failure, this feedback loop malfunctions, causing the kidneys to filter under too much pressure. Over time, that damages the kidneys and worsens fluid retention, which in turn burdens the heart further.
By increasing sodium delivery to a specific sensor in the kidney (the macula densa), Jardiance triggers the kidney to reduce pressure inside its own filters. This lowers the strain on the kidneys, reduces protein leakage into the urine (an early sign of kidney damage), and helps the kidneys regulate fluid balance more normally. The result is a dual protective effect: better kidney function supports better heart function, and vice versa.
Clinical Trial Results
The landmark EMPA-REG OUTCOME trial studied empagliflozin in over 7,000 patients with type 2 diabetes and high cardiovascular risk. The results were striking. Heart failure hospitalization occurred in 2.7% of patients on empagliflozin compared with 4.1% on placebo, a 35% relative risk reduction. When combining heart failure hospitalization with cardiovascular death, the drug cut events from 8.5% to 5.7%, a 34% reduction.
Later trials expanded these findings beyond diabetes. The EMPEROR-Reduced trial tested empagliflozin specifically in heart failure patients with weakened pumping function (reduced ejection fraction), regardless of diabetes status. The benefit appeared to be driven primarily by fewer heart failure hospitalizations rather than a reduction in death from cardiovascular causes. The EMPEROR-Preserved trial then looked at patients whose hearts pumped normally but still had heart failure symptoms (preserved ejection fraction). The primary outcome, a combination of cardiovascular death and heart failure hospitalization, occurred in 13.8% of the empagliflozin group versus 17.1% on placebo. About 31 patients needed to be treated to prevent one cardiovascular event in that population.
One nuance worth noting: in the preserved ejection fraction trial, the benefit was clearest in patients whose pumping function was mildly reduced (ejection fraction between 50% and 60%). Patients with ejection fractions above 60% did not show a statistically significant benefit, though the trend still leaned favorable.
Why It Works Without SGLT2 in the Heart
One of the puzzling things about Jardiance’s heart benefits is that the protein it blocks, SGLT2, isn’t found in heart tissue. Early theories proposed that the drug might also block a different protein in heart cells called the sodium-hydrogen exchanger, which plays a role in how the heart handles calcium and sodium. Disruption of this exchanger could, in theory, protect heart cells from damage. However, more rigorous testing has challenged that idea. Detailed lab studies using cells from healthy hearts found no evidence that empagliflozin inhibits this exchanger or changes sodium levels inside heart cells.
The current understanding is that Jardiance helps the heart indirectly, primarily through its effects on the kidneys, blood vessels, and fluid balance. By reducing how much fluid the heart has to manage, improving vascular function, and protecting the kidneys, it creates conditions that allow a failing heart to work more efficiently. Some researchers also believe it may shift the heart’s energy metabolism in favorable ways, though the precise mechanisms are still being studied.
Side Effects to Be Aware Of
Because Jardiance works by pulling fluid from the body, the most relevant side effect for heart patients is volume depletion. This can show up as dizziness, lightheadedness, or drops in blood pressure, especially when standing. The risk is higher if you already take diuretics (water pills), blood pressure medications like ACE inhibitors or ARBs, or if you’re older. Your prescriber will typically make sure you’re adequately hydrated before starting the medication and may adjust your other drugs to account for the added fluid loss.
A rarer but serious concern is ketoacidosis, a condition where the blood becomes dangerously acidic. This is uncommon in people with type 2 diabetes and heart failure but is more likely in those with a history of pancreatic problems or heavy alcohol use. Jardiance is not used in type 1 diabetes for this reason. Symptoms to watch for include nausea, vomiting, abdominal pain, and unusual fatigue. Because the drug lowers blood sugar through the kidneys rather than through insulin, blood glucose levels during ketoacidosis may appear deceptively normal, which can delay recognition.
Who Benefits Most
Jardiance is approved for adults with heart failure across the spectrum of ejection fractions, with or without diabetes. The strongest evidence supports its use in people whose hearts have reduced pumping ability. For those with preserved ejection fraction, the benefit is more modest and appears greatest when the ejection fraction sits in the lower end of the “preserved” range (around 50% to 60%).
The drug is typically taken once daily as a tablet. For heart failure, the standard dose is 10 mg. It can be taken with or without food and is generally used alongside other guideline-recommended heart failure therapies rather than as a replacement for them.