Jardiance (empagliflozin) is generally well tolerated, but it carries a small number of rare side effects that are serious enough to warrant FDA warnings. These include euglycemic ketoacidosis, a severe genital infection called Fournier’s gangrene, urosepsis, and dangerous drops in blood sugar when combined with certain other diabetes medications. Most people taking Jardiance will never experience any of these, but knowing the warning signs can make a critical difference if they occur.
Ketoacidosis With Normal Blood Sugar
The most counterintuitive rare side effect of Jardiance is a type of diabetic ketoacidosis that happens even when blood sugar readings look normal or only slightly elevated. This is called euglycemic ketoacidosis, and it’s dangerous partly because people don’t recognize it. You or your doctor might assume everything is fine based on a glucose reading, while acid is building up in your blood.
In the large EMPA-REG OUTCOME trial, which followed over 7,000 patients, ketoacidosis occurred in 4 patients on Jardiance compared to 1 on placebo. That’s roughly 0.1% or fewer, but all four cases in the Jardiance group were classified as serious adverse events requiring hospitalization.
Here’s what happens biologically: Jardiance works by blocking the kidney from reabsorbing about 80 to 90% of filtered glucose, so excess sugar leaves through urine. This glucose loss triggers a chain reaction. Your body senses less available sugar, so it lowers insulin output. With less insulin circulating, fat cells release more fatty acids, and the liver converts those fatty acids into ketone bodies. At the same time, Jardiance stimulates glucagon (a hormone that opposes insulin), which further accelerates ketone production. The result is a buildup of acid in the blood while glucose stays deceptively normal.
Making this harder to catch, Jardiance also changes how your kidneys handle ketones, increasing their reabsorption back into the bloodstream rather than excreting them in urine. This means a standard urine ketone test can come back negative even when ketone levels in the blood are dangerously high.
The onset window is unpredictable. Published cases show ketoacidosis developing anywhere from 1 day to over a year after starting the medication.
Who Is Most at Risk
Certain situations significantly raise your risk of this complication. Eating very little, being dehydrated, drinking heavily, undergoing surgery, or having a serious infection can all tip the balance toward ketoacidosis. People with a history of diabetic ketoacidosis or those on reduced-calorie diets should be especially cautious. If you use insulin alongside Jardiance, the lower insulin doses that naturally follow from better glucose control can further increase ketone production.
Sick Day Precautions
Expert consensus guidelines recommend temporarily stopping Jardiance when you’re acutely ill, particularly if you’re vomiting, unable to eat, or dehydrated. The logic is straightforward: illness already stresses the body’s metabolism, and Jardiance’s glucose-lowering and fluid-loss effects can push you toward ketoacidosis under those conditions. Once you’ve been eating and drinking normally for 24 to 48 hours after recovery, it’s typically safe to restart.
Warning signs to watch for include nausea, vomiting, unusual fatigue, abdominal pain, and difficulty breathing. These symptoms deserve urgent medical attention even if your blood sugar meter shows a normal number.
Fournier’s Gangrene
Fournier’s gangrene is a rapidly spreading, life-threatening infection of the tissue around the genitals and perineum (the area between the genitals and anus). It’s exceedingly rare in the general population, occurring at an estimated rate of 1.6 to 3.3 per 100,000 males per year, and it’s even rarer in women. But the FDA identified 12 cases linked to SGLT2 inhibitors (the drug class that includes Jardiance) over a five-year surveillance period from 2013 to 2018. Some of those cases required multiple surgeries, and some were fatal.
The infection typically starts with swelling, redness, or pain in the genital area, accompanied by fever. It can progress to skin death rapidly if not treated with emergency surgery. The FDA updated Jardiance’s label as recently as October 2025 to reinforce this warning. If you notice pain, tenderness, or swelling in the genital or perineal area along with fever or a general feeling of being unwell, seek immediate medical attention. People with a history of genital infections or recurrent urinary tract infections face a higher baseline risk.
Serious Urinary Tract and Kidney Infections
Common urinary tract infections are a known, relatively frequent side effect of Jardiance, occurring at similar rates to placebo in most clinical trials (about 7% in both groups in the EMPA-REG OUTCOME trial). The rare concern is when a UTI escalates into something more severe: pyelonephritis (a kidney infection) or urosepsis (an infection that spreads to the bloodstream).
In clinical trials, complicated urinary tract infections (a category that includes kidney infections and urosepsis) occurred in about 1.4 to 2.0% of patients on Jardiance versus 1.8% on placebo. Those numbers don’t show a dramatic difference, but the FDA’s current prescribing information specifically warns about serious genitourinary infections requiring hospitalization. The risk appears highest in people who have trouble fully emptying their bladder or who have structural abnormalities in the urinary tract, because Jardiance increases sugar in the urine, creating a better environment for bacteria to thrive.
Severe Hypoglycemia With Certain Drug Combinations
Jardiance on its own rarely causes dangerously low blood sugar. The risk changes substantially when it’s combined with insulin or sulfonylureas (another class of diabetes drugs that directly stimulate insulin release). In FDA clinical trial data, severe hypoglycemia (defined as episodes requiring someone else’s assistance) occurred in 1.3% of patients taking the 25 mg dose of Jardiance alongside basal insulin, compared to 0% on placebo with insulin. When combined with multiple daily insulin injections, severe episodes occurred at 0.5% regardless of whether patients were taking Jardiance or placebo.
The practical takeaway: if you’re adding Jardiance to a regimen that already includes insulin or a sulfonylurea, your insulin or sulfonylurea dose may need to be reduced to prevent dangerous lows. This is especially important during the first few weeks of combination therapy.
Amputation Risk: What the Data Shows
You may have heard about amputation concerns with SGLT2 inhibitors. This warning applies primarily to canagliflozin (Invokana), which received a specific FDA safety communication in 2017 after trials showed nearly double the amputation risk compared to placebo. Jardiance does not carry this warning. A meta-analysis comparing empagliflozin to placebo or other diabetes drugs found no significant difference in amputation risk, with an odds ratio of 1.02 (essentially identical risk). People with a history of foot ulcers, peripheral vascular disease, or prior amputations should still be vigilant about foot care, but the available evidence does not suggest Jardiance independently raises this risk.
Dehydration and Low Blood Pressure
Jardiance increases urine output through osmotic diuresis, meaning the extra glucose leaving your kidneys pulls water along with it. This reduces your blood volume. For most people, that’s a mild effect. For older adults, people already taking diuretics, or anyone with kidney disease, the fluid loss can cause dizziness, lightheadedness, or fainting from low blood pressure. While not as dramatic as ketoacidosis or Fournier’s gangrene, dehydration is the mechanism that quietly amplifies several of the other rare risks, from ketoacidosis to kidney infections. Staying well hydrated and paying attention to signs of dehydration, especially in hot weather or during illness, is one of the simplest ways to reduce your overall risk profile on this medication.