Euglycemic DKA on SGLT2 Inhibitors: How to Recognize and Treat This Hidden Emergency
Nov, 6 2025
EDKA Symptom Checker
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This tool helps determine if your symptoms might indicate euglycemic diabetic ketoacidosis (EDKA) - a dangerous condition where blood sugar is normal but ketones are high. EDKA can occur with SGLT2 inhibitors (like Jardiance, Farxiga, Invokana) even when blood sugar appears normal.
EDKA is a medical emergency. If you're experiencing multiple symptoms, seek immediate medical attention.
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Important Information
EDKA is a medical emergency that requires immediate medical attention.
Remember: Normal blood sugar does NOT rule out DKA when taking SGLT2 inhibitors. Ketone testing is critical for diagnosis.
Do not delay care if you have multiple symptoms. Contact your doctor or go to the emergency room immediately.
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. In fact, a dangerous form of DKA can occur with blood sugar levels that look perfectly normal. This is called euglycemic diabetic ketoacidosis (EDKA), and it’s increasingly linked to a popular class of diabetes drugs: SGLT2 inhibitors.
If you or someone you know is taking canagliflozin, dapagliflozin, or empagliflozin-and suddenly feels nauseous, tired, or has abdominal pain-don’t assume it’s just a stomach bug. The blood sugar might be fine, but the body could be drowning in ketones. This isn’t rare. It’s life-threatening. And too many people miss it because they’re looking for the wrong signs.
What Is Euglycemic DKA, Really?
Euglycemic DKA is diabetic ketoacidosis without the high blood sugar. It still has the same deadly ingredients: acidosis (blood pH below 7.3), low bicarbonate (under 18 mEq/L), and high ketones. But instead of glucose levels over 300 mg/dL, you’ll often see readings between 100 and 250 mg/dL. That’s the trap.
This form of DKA was first clearly identified in 2015 after a cluster of cases in U.S. hospitals. Patients on SGLT2 inhibitors-drugs like Farxiga, Jardiance, and Invokana-were showing up with vomiting, confusion, and rapid breathing, but their glucose was only mildly elevated. At first, doctors thought they were misdiagnosed. Then they realized: these drugs were causing a new kind of DKA.
The FDA issued a safety alert in May 2015. Since then, over 1.7 million U.S. patients have been prescribed these drugs. And while the overall risk is low-about 0.16 to 0.76 events per 1,000 patient-years-it’s seven times higher than in people not taking them. Even worse, up to 12% of type 1 diabetes patients using SGLT2 inhibitors off-label develop DKA, and many of those cases are euglycemic.
Why Do SGLT2 Inhibitors Cause This?
SGLT2 inhibitors work by making the kidneys dump glucose into the urine. That lowers blood sugar. But here’s the twist: that same action triggers a chain reaction in the body.
When glucose leaves the body through urine, the body senses a shortage. It responds by ramping up glucagon-a hormone that tells the liver to make more glucose. But because SGLT2 inhibitors block glucose reabsorption, the liver’s extra glucose just gets flushed out too. So instead of fixing the shortage, the body starts breaking down fat for energy.
This fat breakdown produces ketones. And because insulin levels are low (even in type 2 diabetes, insulin resistance doesn’t mean enough insulin is present), the body can’t stop ketone production. The result? Acidosis, even when blood sugar looks normal.
Studies using glucose clamping show this clearly: when researchers kept blood sugar stable while giving SGLT2 inhibitors, glucagon didn’t rise. That proves the ketone surge isn’t from high glucose-it’s from the drug’s effect on the body’s energy balance.
Who’s at Risk?
Anyone on an SGLT2 inhibitor can develop EDKA. But some situations make it far more likely:
- Illness-cold, flu, infection, or fever
- Reduced food intake-dieting, fasting, or not eating due to nausea
- Surgery or major physical stress
- Pregnancy
- Alcohol use
Shockingly, about 20% of EDKA cases happen in people with type 2 diabetes who’ve never had DKA before. They’re not insulin-dependent. They’re not “brittle.” They’re just taking a pill they were told was safe.
And here’s the kicker: off-label use in type 1 diabetes is common. About 8% of type 1 patients in the U.S. are on SGLT2 inhibitors, even though they’re not FDA-approved for this group. That’s a big reason why DKA rates are higher in these patients-5% to 12%-and why so many cases are euglycemic.
What Are the Symptoms?
The symptoms of EDKA are almost identical to regular DKA. But because blood sugar is normal, people often delay care.
- Nausea (85% of cases)
- Vomiting (78%)
- Abdominal pain (65%)
- Deep, rapid breathing (Kussmaul respirations) (62%)
- Extreme fatigue (76%)
- General malaise (91%)
Some people expect a fruity breath odor-the classic “acetone smell” of DKA. But in EDKA, ketone levels are often lower, so that smell may be absent. Relying on breath odor is dangerous. It’s not a reliable clue.
Lab tests show an anion gap metabolic acidosis. Beta-hydroxybutyrate levels are usually above 3 mmol/L. Leukocytosis (high white blood cell count) is common, but it’s often from dehydration, not infection. Don’t mistake it for sepsis.
Why Is It So Hard to Diagnose?
The biggest problem? Cognitive bias. Doctors are trained to think: high glucose = DKA. Normal glucose = not DKA. That’s ingrained. Emergency rooms, urgent cares, even primary care offices often skip ketone testing if glucose is under 250 mg/dL.
A 2015 study in Diabetes Care followed 13 EDKA cases across U.S. hospitals. In every single case, the diagnosis was delayed because providers assumed normal glucose ruled out DKA. Some patients waited hours-or even days-for proper treatment.
Dr. Jane Jeffrie, lead author of that study, put it bluntly: “The absence of hyperglycemia should never rule out DKA in patients on SGLT2 inhibitors. We’ve seen fatal outcomes when providers were falsely reassured.”
How Is It Treated in the Emergency Room?
EDKA is treated like regular DKA-but with critical differences.
1. Start IV fluids immediately. Use 0.9% saline at 15-20 mL/kg in the first hour, then 250-500 mL/hour. Dehydration is severe, and fluid loss is often underestimated.
2. Give insulin-but don’t wait for high glucose. Start insulin at 0.1 units/kg/hour. But here’s the key: you need to add glucose to IV fluids much earlier than in hyperglycemic DKA. Because blood sugar drops fast during treatment, you risk severe hypoglycemia. Most protocols recommend adding dextrose once glucose hits 200-250 mg/dL, but in EDKA, you may need to add it at 150 mg/dL or even sooner.
3. Replace potassium aggressively. Total body potassium is almost always low-even if serum levels look normal. About 65% of EDKA patients need potassium replacement. Check levels hourly and adjust as needed.
4. Test for ketones-right away. Don’t wait. Point-of-care serum beta-hydroxybutyrate testing should happen within 15 minutes of triage in any diabetic patient on an SGLT2 inhibitor with nausea, vomiting, or abdominal pain. Urine ketones aren’t enough-they’re less accurate and slower to change.
Clincial protocols from the Cleveland Clinic and UCSF now require ketone testing as a standard part of the workup for these patients. No exceptions.
How to Prevent It
Prevention is simpler than treatment.
- Stop the drug during illness. If you’re sick, have surgery, or are fasting, hold your SGLT2 inhibitor. Don’t wait for symptoms. The FDA’s label says to stop and seek care if you have ketoacidosis symptoms-but don’t wait for symptoms. Stop the drug at the first sign of illness.
- Check ketones even if glucose is normal. If you’re on an SGLT2 inhibitor and feel unwell, test your blood or urine ketones. Don’t assume normal glucose means you’re safe.
- Don’t skip meals. Low carb intake or fasting increases risk. Keep eating, even if you’re not hungry. Small, frequent meals help.
- Avoid alcohol. Alcohol lowers glucose and increases ketone production. It’s a double risk.
- Don’t start these drugs if you’ve had DKA before. The American Association of Clinical Endocrinology advises against initiating SGLT2 inhibitors in patients with a prior history of DKA.
Patients should be given a written action plan when prescribed these drugs. That plan should include: when to stop the medication, how to test for ketones, and when to go to the ER.
What’s Changing Now?
Since 2015, awareness has improved. EDKA now makes up 41% of all SGLT2 inhibitor-related DKA cases-up from 28%-because doctors are catching more of them. Overall DKA rates have dropped 32% since the FDA warnings.
But the risk remains. New research is looking for early warning signs. A 2023 study found that an elevated ratio of acetoacetate to beta-hydroxybutyrate in the blood can predict EDKA 24 hours before symptoms appear. That’s promising.
Another study, the SGLT2i-EDKA Prediction Study, is testing whether combining HbA1c variability and C-peptide levels can identify high-risk patients. Early results suggest 82% accuracy.
Experts agree: the goal isn’t to stop using SGLT2 inhibitors. They’re effective for weight loss, heart protection, and kidney benefits. The goal is to stop assuming normal glucose means safety.
As Dr. Kieren Mather said at the FDA’s 2023 advisory meeting: “The key to reducing EDKA mortality is not avoiding SGLT2 inhibitors altogether but implementing structured recognition protocols that overcome the cognitive bias of equating DKA with hyperglycemia.”
Frequently Asked Questions
Can you get euglycemic DKA if you have type 2 diabetes?
Yes. While it’s more common in type 1 diabetes, about 20% of euglycemic DKA cases occur in people with type 2 diabetes who have no prior history of DKA. SGLT2 inhibitors can trigger this even in those who don’t use insulin.
Should I stop my SGLT2 inhibitor if I’m sick?
Yes. The FDA and major endocrinology groups recommend stopping SGLT2 inhibitors during acute illness, surgery, or fasting. Don’t wait for symptoms like nausea or vomiting. Stop the drug as soon as you feel unwell and contact your provider.
Is urine ketone testing enough to rule out EDKA?
No. Urine ketone strips are slow, less accurate, and can be misleading. Serum beta-hydroxybutyrate testing is the gold standard. It gives real-time, quantitative results and is essential for diagnosis and monitoring treatment.
Why don’t all doctors know about this?
Many were trained to associate DKA with high blood sugar. The shift to recognizing euglycemic DKA is recent. Medical education is catching up, but emergency departments and primary care clinics still miss cases. Always speak up if you’re on an SGLT2 inhibitor and feel unwell.
Are SGLT2 inhibitors still safe to use?
Yes-if used correctly. These drugs offer real benefits for heart and kidney health. But they require awareness, not avoidance. Know the risks, know the symptoms, test for ketones when sick, and stop the drug during illness. With proper precautions, they remain a valuable tool.
Next Steps
If you’re on an SGLT2 inhibitor, talk to your doctor today. Ask for a written emergency plan. Make sure you know how to test for ketones and when to go to the ER. Keep ketone strips at home. Tell family members what to look for.
If you’re a healthcare provider, don’t wait for high glucose to test for ketones. Make ketone screening standard for any diabetic patient on SGLT2 inhibitors with nausea, vomiting, or abdominal pain. It could save a life.