Jardiance (empagliflozin) interacts with several common medications, supplements, and even dietary choices that can raise your risk of kidney injury, dangerous drops in blood sugar, or a serious condition called ketoacidosis. Some of these interactions aren’t obvious, so understanding them matters whether you’re picking up an over-the-counter painkiller or planning for surgery.
NSAIDs and Pain Relievers
Over-the-counter anti-inflammatory painkillers like ibuprofen (Advil, Motrin) and naproxen (Aleve) are one of the most important drug classes to be cautious with while taking Jardiance. The FDA’s prescribing information specifically lists NSAIDs as a risk factor for acute kidney injury in Jardiance users.
Here’s why: Jardiance works partly by causing your body to lose more fluid through urination. That fluid loss reduces blood volume. NSAIDs, meanwhile, constrict blood vessels in the kidneys. Combine those two effects and kidney blood flow can drop sharply, sometimes enough to trigger acute kidney injury. There have been postmarketing reports of kidney damage severe enough to require hospitalization and dialysis in people taking SGLT2 inhibitors like Jardiance. If you need pain relief, acetaminophen (Tylenol) is generally a safer choice, but talk to your prescriber about what works for your situation.
Diuretics (Water Pills)
Because Jardiance already acts like a mild diuretic, stacking it with prescription water pills amplifies the risk of dehydration and low blood pressure. A study published in JAMA Cardiology found that people taking both empagliflozin and diuretics had a 34% higher risk of volume depletion compared to those on diuretics alone. Symptoms of volume depletion include dizziness when standing, lightheadedness, fainting, and feeling unusually thirsty or weak.
Loop diuretics like furosemide (Lasix) and thiazide diuretics like hydrochlorothiazide are the most common culprits. Many people with diabetes also have high blood pressure or heart failure and take these medications, so the combination comes up frequently. Your doctor may need to adjust your diuretic dose when starting Jardiance, and staying well hydrated becomes especially important.
Blood Pressure Medications: ACE Inhibitors and ARBs
ACE inhibitors (names ending in “-pril,” like lisinopril) and ARBs (names ending in “-sartan,” like losartan) are extremely common in people with diabetes because they protect the kidneys long-term. But the FDA label for Jardiance flags both drug classes as risk factors for acute kidney injury when combined with empagliflozin. All three medications reduce pressure or volume in the kidneys through different mechanisms, and together they can push kidney function into a vulnerable range, particularly during illness, dehydration, or hot weather.
This doesn’t mean you can’t take them together. Many people safely do. But the combination requires closer monitoring of kidney function, and you should be extra alert to signs of dehydration.
Insulin and Sulfonylureas
If you’re already taking insulin or a sulfonylurea (such as glipizide, glyburide, or glimepiride), adding Jardiance on top can cause your blood sugar to drop too low. Jardiance lowers blood sugar through a completely different pathway than these medications, so the effects stack. Hypoglycemia can cause shakiness, confusion, sweating, rapid heartbeat, and in severe cases, loss of consciousness.
When Jardiance is added to insulin or a sulfonylurea, your prescriber will typically lower the dose of the other medication to compensate. If you notice frequent episodes of low blood sugar after starting Jardiance, that’s a sign the doses need further adjustment.
Alcohol
Drinking alcohol while on Jardiance raises the risk of a condition called euglycemic diabetic ketoacidosis, where dangerous levels of acid build up in your blood even though your blood sugar readings look normal. Alcohol disrupts the body’s ability to process carbohydrates for energy, pushing it toward burning fat instead. Jardiance independently promotes the same metabolic shift. Together, they can tip the balance toward ketoacidosis without the high blood sugar readings that would normally serve as a warning sign.
Chronic heavy drinking is the highest risk scenario, but even acute alcohol intoxication can trigger the problem. Symptoms to watch for include nausea, vomiting, abdominal pain, unusual fatigue, and difficulty breathing. Because blood sugar may appear normal, this condition is easy to miss and can become dangerous quickly.
Very Low-Carb and Ketogenic Diets
A ketogenic or very low-carbohydrate diet creates the same metabolic setup that makes euglycemic ketoacidosis possible. When carbohydrate intake is extremely low, your body relies more heavily on fat for fuel, producing ketones as a byproduct. Jardiance amplifies this process by causing glucose to leave the body through urine, further reducing the carbohydrates available for energy. A review in Frontiers in Pharmacology identified low-carbohydrate diets as a factor that can interact with SGLT2 inhibitors and amplify ketoacidosis risk.
This doesn’t mean you need to eat a high-carb diet on Jardiance, but extreme carbohydrate restriction is risky. If you’re interested in a low-carb approach, work with your healthcare team to find a carbohydrate level that’s safe with your medication.
Supplements and Herbal Products
The Mayo Clinic’s drug information for empagliflozin advises against taking any prescription, over-the-counter, or herbal supplements without discussing them with your doctor first. One specific interaction listed is with alpha-lipoic acid (also called thioctic acid), a supplement commonly marketed for nerve pain and blood sugar support. Alpha-lipoic acid can lower blood sugar on its own, and combining it with Jardiance may increase the risk of hypoglycemia.
Other supplements that independently lower blood sugar, such as berberine, bitter melon, and fenugreek, carry a similar theoretical concern. Herbal diuretics like dandelion root or green tea extract could compound Jardiance’s fluid-loss effects. The research on these combinations is limited, which is exactly why caution is warranted.
Situations That Require Stopping Jardiance
Certain temporary situations call for pausing Jardiance entirely rather than just being cautious about interactions.
- Scheduled surgery: The American Diabetes Association recommends stopping Jardiance at least three days before any planned surgical procedure. Surgery, fasting, and anesthesia all increase the risk of ketoacidosis, and Jardiance lingering in your system makes that risk significantly worse.
- Acute illness or fasting: The FDA label recommends considering temporarily stopping Jardiance whenever you have reduced oral intake (from illness or fasting) or significant fluid losses from vomiting, diarrhea, or excessive heat exposure.
- Severely reduced kidney function: Jardiance is not recommended for blood sugar control when kidney filtration rate (eGFR) falls below 30, because the drug simply can’t work effectively at that level. For heart failure, the threshold is lower, and patients in clinical trials continued use down to an eGFR of 20.
The common thread across nearly all of Jardiance’s interactions is fluid balance. The drug removes glucose through your urine, pulling water along with it. Anything else that reduces fluid volume, stresses your kidneys, or shifts your metabolism away from carbohydrates can turn that normally manageable effect into something dangerous. Staying well hydrated and keeping your prescriber informed about everything else you take, including supplements and OTC medications, are the most practical steps you can take to use Jardiance safely.