Euglycemic DKA on SGLT2 Inhibitors: How to Recognize and Treat It in an Emergency

Most people think diabetic ketoacidosis (DKA) means high blood sugar. That’s what they’re taught. That’s what they test for. But if you’re taking an SGLT2 inhibitor - like Farxiga, Jardiance, or Invokana - and you feel sick, your blood sugar might be perfectly normal. And that’s when things get dangerous.

What Is Euglycemic DKA?

This isn’t rare. Since 2015, over 1.7 million people in the U.S. have been prescribed SGLT2 inhibitors. Around 0.16 to 0.76 cases of EDKA happen per 1,000 patient-years in type 2 diabetes. That’s a sevenfold increase compared to those not on these drugs. Even worse, up to 12% of type 1 diabetes patients on off-label SGLT2 inhibitors develop DKA - and many don’t show high glucose.

EDKA isn’t a new disease. It’s just a new way DKA shows up. The FDA added a boxed warning to all SGLT2 inhibitor labels in 2015 after reports of fatal cases where doctors missed the diagnosis because glucose looked fine. That warning says it plainly: "Stop the medication and seek immediate help if you have symptoms of ketoacidosis, even if your blood sugar is normal."

Why Does This Happen?

This creates a perfect storm: your body burns fat for energy, making ketones like acetone and beta-hydroxybutyrate. But because glucose is being flushed out, your blood sugar stays low or just mildly elevated. You’re in ketoacidosis, but your glucose reading says "all clear."

Studies using glucose clamping - where glucose is held steady during SGLT2 inhibitor use - show that when blood sugar doesn’t drop, glucagon doesn’t spike. That proves the drop in glucose is what triggers the ketone surge. It’s not the drug itself. It’s the body’s reaction to the glucose loss.

Who’s at Risk?

• Illness (infections, flu, COVID-19)
• Surgery or major stress
• Reduced food intake (dieting, fasting, vomiting)
• Alcohol use
• Pregnancy
• Stopping insulin or reducing doses

Even if you’re feeling fine, if you’re on an SGLT2 inhibitor and you skip meals or get sick, your risk goes up. That’s why doctors now recommend stopping these drugs at least 3 days before surgery or during any acute illness.

How to Spot It - The Red Flags

• Nausea and vomiting (85% of cases)
• Abdominal pain (65%) - often mistaken for food poisoning or appendicitis
• Unusual tiredness or weakness (76%)
• Difficulty breathing or deep, fast breaths (Kussmaul respirations, 62%)
• General malaise (91%)

And here’s the trap: your blood sugar might be 180 mg/dL. Your doctor sees that and says, "You’re not in DKA." But your ketones? They’re through the roof. Beta-hydroxybutyrate levels above 3 mmol/L confirm it. Your blood pH will be below 7.3. Bicarbonate below 18 mEq/L. Anion gap metabolic acidosis.

Don’t wait for the fruity smell. It’s not always there. Don’t wait for glucose to hit 300. By then, it’s too late.

Emergency Care: What Actually Works

Step 1: Test ketones immediately. If you’re on an SGLT2 inhibitor and you have nausea, vomiting, or abdominal pain, don’t wait. Get a blood ketone test (beta-hydroxybutyrate) right away. Urine strips are too slow and unreliable. Hospitals like Cleveland Clinic now require ketone testing within 15 minutes of triage for any diabetic on these drugs with these symptoms.

Step 2: Start IV fluids. Use 0.9% saline at 15-20 mL/kg in the first hour. But don’t overdo it. You’re dehydrated, but your body is already low on glucose. Too much fluid can dilute your sodium and worsen your condition.

Step 3: Give insulin - but don’t wait for high glucose. Start insulin at 0.1 units/kg/hour. But here’s the key: as soon as your blood sugar drops below 200 mg/dL, switch to dextrose-containing fluids (like D5W). In classic DKA, you wait until glucose hits 250 before adding sugar. In EDKA, you add it early - sometimes even before you start insulin - to prevent dangerous drops.

Step 4: Replace potassium. Your serum potassium might look normal. But you’re likely low on total body potassium. About 65% of EDKA patients have hidden potassium depletion. Give it early, monitor often.

And never, ever stop monitoring. Blood sugar can crash fast. Ketones can linger. Acidosis takes hours to correct. This isn’t a quick fix.

Prevention: What Patients Need to Know

• If you’re on an SGLT2 inhibitor, keep ketone strips at home. Test them when you’re sick, even if your sugar is normal.
• Stop the medication if you’re fasting, having surgery, or seriously ill. Talk to your doctor first - don’t just quit cold.
• Don’t skip meals. Even if you’re trying to lose weight, eat something. Low carbs + SGLT2 inhibitor = high ketone risk.
• Limit alcohol. It suppresses liver glucose production and worsens acidosis.
• If you have type 1 diabetes and are on an SGLT2 inhibitor off-label, make sure your insulin dose is tight. Don’t reduce it thinking the drug will cover you.

The American Diabetes Association says it clearly: "Evaluate for ketones in any diabetic on SGLT2 inhibitors who has nausea, vomiting, or malaise - regardless of glucose level."

The Bigger Picture

Since 2015, awareness has cut overall EDKA cases by 32%. But here’s the twist: EDKA now makes up 41% of all SGLT2 inhibitor-related DKA cases - up from 28%. That means we’re getting better at spotting it. But we’re still missing too many.

Researchers are now testing tools to predict who’s at highest risk. One study found that people with unstable HbA1c and low C-peptide (meaning their pancreas doesn’t make much insulin) are 82% more likely to develop EDKA. Another found that a high ratio of acetoacetate to beta-hydroxybutyrate in the blood can predict EDKA 24 hours before symptoms start.

But none of that matters if you don’t test ketones when you’re sick. No algorithm replaces a simple blood ketone test.

Final Takeaway

Test your ketones. If they’re high, go to the ER. Don’t wait. Don’t hope it passes. Your glucose level is lying to you.

And if you’re a healthcare provider - stop relying on glucose alone. If your patient is on an SGLT2 inhibitor and looks sick, treat for DKA until proven otherwise. That’s the new standard.