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

Most people with diabetes know that diabetic ketoacidosis (DKA) means high blood sugar, confusion, fruity breath, and vomiting. But what if your blood sugar is normal - even low - and you’re still in DKA? That’s euglycemic DKA, and it’s not rare anymore. In fact, it’s becoming more common because of a class of diabetes drugs called SGLT2 inhibitors. These medications - like Jardiance, Farxiga, and Invokana - are popular because they help lower blood sugar, reduce weight, and protect the heart. But they come with a dangerous hidden risk: euglycemic DKA.

What Is Euglycemic DKA?

Euglycemic DKA, or EDKA, is a life-threatening condition where your body floods with ketones - toxic acids made from fat - but your blood sugar stays below 250 mg/dL. This is the opposite of classic DKA, where blood sugar often soars above 300 or even 500 mg/dL. The name says it all: "euglycemic" means normal glucose, "DKA" means diabetic ketoacidosis. It’s a trap. Normal blood sugar makes you - and your doctor - think everything’s fine. But inside your body, your cells are starving for fuel, and your liver is churning out ketones like crazy.

This happens because SGLT2 inhibitors work by making your kidneys dump sugar out in your urine. That sounds good - until it doesn’t. You lose glucose, your blood sugar drops, and your body thinks it’s in starvation mode. Even if you ate breakfast, your cells act like you haven’t eaten in days. Your pancreas releases more glucagon (the hormone that raises blood sugar) and less insulin. That imbalance turns your fat into fuel, and fast. Ketones build up. Your blood gets acidic. And you can crash.

Who’s at Risk?

SGLT2 inhibitors are approved for type 2 diabetes. But they’re also used off-label in some type 1 patients - about 8% of them - even though they’re not FDA-approved for that. And that’s where things get riskier. Studies show that type 1 patients on these drugs have a 5% to 12% chance of developing DKA, even if they’ve never had it before. But type 2 patients aren’t safe either. About 20% of EDKA cases happen in people with type 2 diabetes who had no history of DKA. That’s shocking. These aren’t high-risk patients. They’re people who took their pills, ate normally, and woke up feeling sick.

Here’s what pushes someone over the edge:

• Getting sick (flu, infection, COVID-19)
• Skipping meals or eating too little
• Having surgery or a major medical procedure
• Drinking alcohol
• Pregnancy
• Stopping insulin or reducing it too much

One patient I read about was a 58-year-old man with type 2 diabetes. He was on dapagliflozin, had a cold, ate less for two days, and stopped checking his blood sugar because he felt "fine." He ended up in the ER with a pH of 7.1, ketones at 8.2 mmol/L, and blood sugar at 180 mg/dL. He didn’t have a fever. His glucose monitor didn’t alarm him. He didn’t know he was dying.

Why Is It So Hard to Spot?

The biggest danger of EDKA is that it looks like nothing. No red flags. No high blood sugar. No "DKA alert." Patients show up with nausea, vomiting, belly pain, and exhaustion. They sound like they have the flu. Doctors see normal glucose and think, "Not DKA." They give anti-nausea meds, send them home, and the patient comes back worse - or not at all.

Studies show that 13 cases of EDKA were missed in U.S. clinics because providers assumed high glucose was required. One patient died. Another needed a week in intensive care. The FDA got so alarmed they added a boxed warning to every SGLT2 inhibitor label: "Stop taking this medication and get help right away if you have symptoms of ketoacidosis, even if your blood sugar is normal."

Here’s what patients actually feel:

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

And here’s the cruel twist: you might not smell like ketones. In classic DKA, the acetone gives off that fruity, nail-polish-remover odor. But in EDKA, ketone levels are lower, and the smell is often gone. So no warning scent. Just silence. And that’s why you need to test for ketones - not just glucose.

How Is It Diagnosed?

You can’t rely on a finger-stick glucose meter. You need three things:

1. Blood pH under 7.3 - This shows your blood is too acidic.
2. Bicarbonate under 18 mEq/L - Confirms metabolic acidosis.
3. Ketones in blood or urine - Beta-hydroxybutyrate above 3 mmol/L is a red flag.

Many ERs now use point-of-care ketone meters that measure beta-hydroxybutyrate. These give results in under 10 minutes. If you’re on an SGLT2 inhibitor and have nausea or vomiting, this test should be done immediately - not after checking glucose, not after waiting for labs. Right away.

Don’t be fooled by high anion gap or leukocytosis (elevated white blood cells). These can happen in EDKA, but they’re not specific. They might mean infection - or just dehydration. Only ketones confirm the diagnosis.

Emergency Treatment: What Works

Treatment is similar to classic DKA - but with a twist. You can’t just give insulin and expect glucose to drop. In EDKA, glucose can plunge dangerously low during treatment. So here’s the protocol:

1. Stop the SGLT2 inhibitor. No exceptions. Keep it stopped until fully recovered.
2. Start IV fluids. Use 0.9% saline. Give 15-20 mL/kg in the first hour. Keep giving 250-500 mL/hour after that. Dehydration is real, and your kidneys are already stressed.
3. Give insulin - but don’t wait for high sugar. Start at 0.1 units/kg/hour. You don’t need glucose above 250 to begin. Insulin stops ketone production.
4. Start glucose-containing fluids early. When blood sugar hits 200 mg/dL, switch to 5% dextrose with insulin. If it drops below 150, add dextrose even sooner. You’re trying to feed your cells, not starve them.
5. Replace potassium aggressively. Even if your serum potassium looks normal, you’re likely low. Total body potassium is often 50-100 mmol below normal. Give 20-40 mEq per hour as needed. Monitor every 2 hours.

One mistake I see too often: waiting for glucose to rise before giving dextrose. That’s deadly. By the time glucose hits 250, the patient may already be in cardiac arrest from hypoglycemia. Better to give dextrose at 200 - even 180 - than wait.

Prevention: What Patients and Doctors Must Do

This isn’t about stopping SGLT2 inhibitors. It’s about using them safely.

• Never take SGLT2 inhibitors during illness. If you have a fever, infection, or surgery planned - stop the drug 3-5 days before and don’t restart until you’re eating normally again.
• Check ketones when you’re sick. Even if your glucose is 150. Use a blood ketone meter if you have one. Urine strips work, but they’re slower and less accurate.
• Don’t skip meals. If you’re not eating, your body will burn fat. That’s what SGLT2 inhibitors already encourage. Double the risk.
• Know your symptoms. Nausea? Vomiting? Belly pain? Fatigue? Don’t assume it’s the flu. Test for ketones. Call your doctor. Go to the ER.
• Get educated. Ask your provider: "Should I stop my SGLT2 inhibitor if I get sick?" If they say "no," find someone who knows better.

There’s also a new tool on the horizon. A 2023 study found that the ratio of acetoacetate to beta-hydroxybutyrate in the blood can predict EDKA 24 hours before symptoms start. That’s huge. In the future, high-risk patients might get home test kits to monitor this ratio. But for now - test ketones when you’re sick. Period.

The Bigger Picture

SGLT2 inhibitors are powerful drugs. They save lives. They reduce heart failure, kidney damage, and death in type 2 diabetes. But they’re not risk-free. And we’ve been too slow to teach patients and doctors about EDKA.

The FDA now requires patient guides with every SGLT2 inhibitor prescription. They say: "If you feel unwell, stop the drug and get help - even if your sugar is normal." That’s not just a warning. It’s a lifesaving instruction.

And here’s the truth: if you’re on one of these drugs, you’re not just a diabetic. You’re a patient with a hidden risk. You need to know the signs. You need to test ketones. You need to speak up. Because in this case, normal blood sugar isn’t safe. It’s a lie.