Euglycemic DKA on SGLT2 Inhibitors: How to Recognize and Treat This Hidden Emergency

Most doctors still think diabetic ketoacidosis (DKA) means high blood sugar. That’s the old rule. But if you’re taking an SGLT2 inhibitor-like Farxiga, Jardiance, or Invokana-and you feel sick, your blood sugar might be normal. And that’s when things get dangerous.

Euglycemic DKA isn’t rare. It’s hiding in plain sight. About 1 in 3 cases of DKA in people on these drugs happens with blood glucose under 250 mg/dL. That’s not a fluke. It’s a pattern. And it’s killing people because no one checks ketones when the glucose reading looks fine.

What Is Euglycemic DKA?

Euglycemic DKA is diabetic ketoacidosis without the high blood sugar. You still get acidosis-your blood gets too acidic. Your body still floods with ketones. But your glucose stays between 100 and 250 mg/dL. Normal range. So you, your family, even your doctor, might think you’re okay.

This isn’t theoretical. In 2015, the FDA issued a warning after 13 cases were found in U.S. clinics. Nine patients. Thirteen episodes. All on SGLT2 inhibitors. Seven had type 1 diabetes. Two had type 2. None had blood sugar above 250 mg/dL. That’s when the medical world had to change its playbook.

The problem? SGLT2 inhibitors make your kidneys flush out glucose. That lowers blood sugar. But it also tricks your body into thinking it’s starving. Your pancreas releases more glucagon. Your fat breaks down. Ketones pile up. And you’re in DKA-even if your glucose looks perfect.

Why SGLT2 Inhibitors Trigger This

SGLT2 inhibitors were designed to help type 2 diabetes by making you pee out sugar. They work. They reduce heart failure risk. They help with weight. But they also mess with your body’s fuel balance.

Here’s how it breaks down:

• You take the drug → glucose leaves through urine → blood sugar drops
• Your body thinks it’s low on fuel → glucagon rises, insulin drops
• Fat gets broken down → ketones flood your blood
• Acid builds up → metabolic acidosis sets in

Even if you’re eating normally, your liver can’t make enough glucose to keep up. The drug blocks the backup system. That’s why you can get DKA without ever being hyperglycemic.

And it’s not just people with type 1 diabetes. About 20% of cases happen in people with type 2 who’ve never had DKA before. That’s the scary part. You think you’re safe because you’re not insulin-dependent. You’re wrong.

Signs You’re in Trouble

These symptoms don’t care about your glucose meter.

• Nausea (85% of cases)
• Vomiting (78%)
• Abdominal pain (65%)
• Deep, fast breathing (Kussmaul respirations, 62%)
• Extreme fatigue (76%)
• General malaise (91%)

You might feel like you have the flu. Or food poisoning. Or a bad stomach bug. But if you’re on an SGLT2 inhibitor and you’re feeling this way, don’t wait. Don’t assume it’s just a virus. Don’t check your glucose and breathe easy because it’s 180 mg/dL.

That’s the trap. The glucose is normal. So you think, “It’s not DKA.” But DKA doesn’t need high sugar anymore. That rule is dead.

And no, you can’t rely on fruity breath. Some people have it. Many don’t. It’s not a reliable sign. Only ketone testing tells the truth.

How Doctors Miss It

Emergency rooms across the U.S. still use glucose as the gatekeeper for DKA. If it’s under 250, they don’t test ketones. They don’t check anion gap. They don’t look at bicarbonate.

A 2015 study in Diabetes Care showed that in every single case of SGLT2-related euglycemic DKA, treatment was delayed because doctors trusted the glucose reading. One patient died. Another had a cardiac arrest. All because no one thought to check ketones.

The FDA’s 2015 warning said it plainly: “Ketoacidosis can occur with blood glucose levels below 250 mg/dL.” But that warning hasn’t fully reached every ER, every clinic, every urgent care center.

Dr. Jane Jeffrie, who led the 2015 study, put it bluntly: “The absence of hyperglycemia should never rule out DKA.”

And yet, most providers still don’t test for ketones unless glucose is over 300. That’s outdated. That’s dangerous.

How to Diagnose It

If you’re on an SGLT2 inhibitor and you have nausea, vomiting, or unexplained fatigue, you need three things checked:

1. Blood glucose - even if it’s normal
2. Serum ketones - beta-hydroxybutyrate, not urine strips
3. Arterial blood gas or venous bicarbonate - look for pH under 7.3 or bicarbonate under 18 mEq/L

Urine ketone strips? Useless. They’re slow. They’re inaccurate. They miss early ketosis. Serum beta-hydroxybutyrate is the gold standard. Levels above 3 mmol/L mean you’re in DKA.

Also check your anion gap. If it’s over 12, you’ve got metabolic acidosis. Combine that with ketones and symptoms? You’ve got euglycemic DKA.

Don’t be fooled by high white blood cell counts. That’s not infection. It’s dehydration. It’s stress. It’s the body reacting to acidosis.

Emergency Treatment: What Works

Treatment is similar to classic DKA-but with key differences.

First: fluids. Start with 0.9% saline at 15-20 mL/kg in the first hour. But don’t overdo it. You’re not dehydrated like a classic DKA patient. Your volume status is often better.

Second: insulin. Give 0.1 units/kg/hour. But here’s the twist: start glucose-containing fluids early. In classic DKA, you wait until glucose drops below 250 to add dextrose. In euglycemic DKA, you might need it after the first hour. Your blood sugar can crash fast. You don’t want to go from 180 to 50 in two hours.

Third: potassium. Almost two-thirds of these patients have low total body potassium-even if their blood level looks normal. You’ll need to replace it aggressively. Don’t wait for the lab to show low potassium. Start early.

Fourth: stop the SGLT2 inhibitor. Immediately. Don’t wait. Don’t ask. Just stop it.

And don’t forget: check for other causes. Lactic acidosis, alcohol, sepsis. They can mimic this. But if ketones are high and acidosis is present, treat for DKA first.

Who’s at Highest Risk?

It’s not just type 1 diabetes. Here’s who needs to be extra careful:

• Anyone on SGLT2 inhibitors during illness (infection, flu, COVID-19)
• People who skip meals or eat very little
• Patients preparing for surgery
• Women who are pregnant
• Those who drink alcohol

Even if you’re type 2, have no history of DKA, and feel fine-stop your SGLT2 inhibitor if you get sick. Don’t wait for symptoms. Don’t hope it’ll pass. Just stop.

And if you’re type 1? Off-label use of SGLT2 inhibitors is common. About 8% of type 1 patients are on them. DKA rates in this group? Between 5% and 12%. That’s not low. That’s a ticking clock.

Prevention: What You Need to Do

Prevention is simple. But it’s not taught enough.

• Always check ketones if you’re sick-even if your glucose is normal.
• Stop your SGLT2 inhibitor when you’re ill, fasting, or having surgery.
• Keep eating carbs during stress. Don’t go low-carb to “help your diabetes.” That’s a recipe for disaster.
• Have ketone strips or a meter at home. Know how to use them.
• Tell every doctor you see that you’re on an SGLT2 inhibitor. Write it on your medical alert bracelet.

The FDA requires that every SGLT2 inhibitor package says: “Stop taking this medicine and get medical help right away if you have symptoms of ketoacidosis-even if your blood sugar is normal.”

But if you don’t know what those symptoms are? You won’t stop. You won’t go to the ER. You’ll wait. And that’s how people die.

What’s Changing Now?

Good news: awareness is rising. Since 2015, overall DKA cases on SGLT2 inhibitors have dropped by 32%. But here’s the catch: euglycemic DKA now makes up 41% of all cases-up from 28% in 2015. That means more people are being diagnosed correctly. But the risk hasn’t gone away.

Researchers are testing new tools. A 2023 study found that the ratio of acetoacetate to beta-hydroxybutyrate can predict EDKA 24 hours before symptoms start. That’s huge. But it’s not available yet.

Another project, the SGLT2i-EDKA Prediction Study, is tracking over 1,200 patients. Early results suggest that if your HbA1c swings a lot and your C-peptide is low, you’re at higher risk. That could lead to screening tools in the next few years.

But right now? The only tool you need is your brain. And a ketone meter.

The Bottom Line

SGLT2 inhibitors are powerful drugs. They save lives. But they can kill if you don’t know how they work.

Euglycemic DKA is real. It’s dangerous. And it’s underdiagnosed.

If you’re on one of these drugs, you must know: normal glucose doesn’t mean safe. Ketones don’t care about your meter. They care about your body’s fuel state.

Check ketones when you’re sick. Stop the drug when you’re unwell. Tell your doctors. Don’t wait for the textbook signs. The textbook changed. You have to change with it.

One more thing: if you’re a doctor-don’t assume. Test. Even if the glucose is fine. You might just save a life.

For more information, refer to the American Diabetes Association’s 2022 Standards of Medical Care in Diabetes and the FDA’s safety communications on SGLT2 inhibitors. Always consult your healthcare provider before making changes to your medication.