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

Most doctors and patients assume diabetic ketoacidosis (DKA) only happens when blood sugar is sky-high-above 250 mg/dL. But that’s not always true. A dangerous, often missed form of DKA called euglycemic DKA can occur even when blood sugar looks normal. And it’s becoming more common in people taking SGLT2 inhibitors like Farxiga, Jardiance, and Invokana. This isn’t rare. It’s not a fluke. It’s a real, life-threatening emergency that’s slipping through the cracks because everyone’s looking for high glucose-and not finding it.

What Is Euglycemic DKA?

Euglycemic diabetic ketoacidosis (EDKA) is DKA without the high blood sugar. It’s still DKA: your blood is acidic, your ketones are high, and your body is breaking down fat for fuel because it thinks it’s starving. But your glucose? It’s under 250 mg/dL-sometimes even in the 100-180 range. That’s the trap. Normal glucose tricks you into thinking you’re safe.

This isn’t theoretical. In 2015, the FDA issued a warning after 13 cases were found across U.S. clinics. Nine people got sick. Seven had type 1 diabetes. Two had type 2. All were on SGLT2 inhibitors. Since then, studies show EDKA makes up 2.6% to 3.2% of all DKA hospital admissions. For people on SGLT2 drugs, the risk is seven times higher than for those not taking them.

The problem isn’t the drug itself. It’s how it works. SGLT2 inhibitors make your kidneys dump sugar into your urine. That lowers blood glucose-good for weight loss and heart protection. But here’s the catch: your body doesn’t know you’re still getting insulin. So your pancreas keeps releasing glucagon, the hormone that tells your liver to make more glucose. But since the drug blocks sugar from being reabsorbed, your liver’s glucose just gets flushed out. You end up with low glucose, high glucagon, and no insulin signal to stop fat breakdown. Result? Ketones pile up. Acid builds up. You get sick.

Who’s at Risk?

You don’t have to have type 1 diabetes to get EDKA. In fact, about 20% of cases happen in people with type 2 diabetes who’ve never had DKA before. But the risk spikes if you’re:

• Ill with an infection, flu, or COVID-19
• Skipping meals or eating very little
• Recovering from surgery
• Pregnant
• Drinking alcohol
• On insulin therapy (even if you’re not fully dependent)

And here’s the scary part: SGLT2 inhibitors aren’t approved for type 1 diabetes-but 8% of type 1 patients are still prescribed them off-label. In this group, DKA rates jump to 5%-12%. That’s not a small number. That’s a red flag.

Symptoms: It Doesn’t Look Like DKA

If you’re used to DKA looking like this: extreme thirst, frequent urination, fruity breath, confusion-you’re in for a surprise. EDKA doesn’t follow the script.

People with EDKA show up with:

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

And here’s the kicker: the fruity breath you hear about in textbooks? It’s often absent. Why? Because ketone levels are lower than in classic DKA. But that doesn’t mean it’s less dangerous. In fact, it’s more dangerous because no one suspects it.

One patient, a 58-year-old man with type 2 diabetes on Jardiance, came to the ER with vomiting and belly pain. His blood sugar was 165 mg/dL. The ER team didn’t test ketones. He was sent home with a diagnosis of “gastroenteritis.” He returned two days later in cardiac arrest. He didn’t survive.

How to Diagnose It

The only way to catch EDKA is to test for ketones-even if glucose looks fine. That’s the rule now.

Diagnostic criteria are simple:

• Blood glucose < 250 mg/dL
• Arterial pH < 7.3
• Serum bicarbonate < 18 mEq/L
• Elevated serum ketones (beta-hydroxybutyrate > 3 mmol/L)

Don’t rely on urine strips. They’re slow and inaccurate. Use a blood ketone meter-like the Precision Xtra or Nova StatStrip. Hospitals should have these at triage. The Cleveland Clinic’s emergency protocol requires all diabetic patients on SGLT2 inhibitors with nausea or vomiting to get a blood ketone test within 15 minutes. No exceptions.

Also check your anion gap. It’s usually widened (>12 mEq/L). Lactic acid might be elevated too. Don’t confuse it with sepsis. Leukocytosis? Common. But it’s usually from dehydration, not infection.

Emergency Treatment: It’s Different Than You Think

Treatment follows DKA guidelines-but with key twists.

Step 1: Fluids. Start with 0.9% saline at 15-20 mL/kg over the first hour. Then 250-500 mL/hour. But don’t wait for dehydration to be severe. EDKA patients are often dehydrated from vomiting and glycosuria-but they look okay because their glucose isn’t high.

Step 2: Insulin. Start at 0.1 units/kg/hour. But here’s the critical difference: you need to add dextrose much earlier than in classic DKA. In traditional DKA, you hold glucose until blood sugar drops below 200-250 mg/dL. In EDKA, glucose is already low. If you don’t add dextrose early, you’ll crash into dangerous hypoglycemia. Start 5% dextrose once glucose hits 200 mg/dL or lower-even if ketones are still high.

Step 3: Potassium. Almost everyone is low on potassium-even if their blood test looks normal. Why? Insulin drives potassium into cells. But your total body potassium is already depleted from glycosuria. You’ll need 20-40 mEq of potassium per liter of IV fluid. Monitor levels every 2-4 hours.

Step 4: Stop the SGLT2 inhibitor. Immediately. Don’t wait. Don’t think it’s “just one dose.” The drug is still active in your system for hours. Keep it stopped until you’re fully recovered and off IV fluids.

Step 5: Watch for complications. Cerebral edema is rare in adults but possible. Kidney injury from volume loss? Common. Don’t overcorrect acidosis with bicarbonate. It’s rarely needed.

Prevention: What Patients Need to Know

The best way to avoid EDKA is to know when to pause the drug.

Patients on SGLT2 inhibitors should be told:

• If you’re sick-flu, infection, surgery-stop your SGLT2 inhibitor and call your doctor.
• If you’re vomiting, can’t eat, or feel extremely tired, test your ketones-even if your glucose is normal.
• Don’t skip meals. Even if you’re trying to lose weight, your body needs fuel when you’re stressed.
• Never drink alcohol while on these drugs, especially if you’re ill.
• Keep a blood ketone meter at home. It’s not expensive. It’s lifesaving.

Pharmacists should hand out printed instructions with every SGLT2 prescription. The FDA now requires this. The package insert must say: “Stop taking this medication and seek immediate medical attention if you have symptoms of ketoacidosis, even if your blood sugar is normal.”

The Bigger Picture

SGLT2 inhibitors are powerful drugs. They lower heart failure risk. They protect kidneys. They help with weight. But they’re not risk-free. And the risk of EDKA is real, underdiagnosed, and deadly.

As of 2023, SGLT2 inhibitors make up 25% of new diabetes prescriptions in the U.S. Dapagliflozin (Farxiga) is the most prescribed, followed by empagliflozin (Jardiance). That means millions of people are at risk.

But awareness is improving. Since 2015, EDKA cases have dropped 32% overall-thanks to better education. But now, EDKA makes up 41% of all SGLT2-related DKA cases. That means we’re getting better at spotting it-but it’s still happening.

Research is moving forward. A 2023 study found that the ratio of two ketones-acetoacetate to beta-hydroxybutyrate-can predict EDKA 24 hours before symptoms start. That could lead to early alerts. Another study is testing whether HbA1c variability and C-peptide levels can identify high-risk patients with 82% accuracy.

The bottom line? SGLT2 inhibitors aren’t the enemy. But assuming DKA means high glucose is. That’s the bias that kills.

What You Should Do Right Now

If you’re on an SGLT2 inhibitor:

• Ask your doctor for a ketone meter and learn how to use it.
• Write down the warning signs: nausea, vomiting, belly pain, fatigue.
• Know when to stop the drug: illness, fasting, surgery, alcohol.
• Keep your emergency contact number handy.

If you’re a clinician:

• Test ketones in every diabetic patient on SGLT2 inhibitors with nausea or vomiting-even if glucose is normal.
• Don’t wait for acidosis to be severe. Start fluids and insulin early.
• Don’t assume normal glucose means safe.

This isn’t a rare complication. It’s a silent killer. And it’s preventable-if you know what to look for.