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

When someone with diabetes takes an SGLT2 inhibitor like Farxiga, Jardiance, or Invokana, they’re often told to expect lower blood sugar, weight loss, and better heart and kidney protection. But there’s a dangerous side effect that doesn’t show up on a standard glucose meter-and it’s killing people who don’t even realize they’re in danger. This is euglycemic diabetic ketoacidosis (EDKA): a life-threatening condition where the body floods with ketones, acid builds up in the blood, and yet, blood sugar stays stubbornly normal. It’s not rare. It’s not theoretical. And if you’re on an SGLT2 inhibitor, you need to know how to spot it before it’s too late.

What Is Euglycemic DKA, Really?

Euglycemic DKA is diabetic ketoacidosis without the high blood sugar. Traditional DKA happens when insulin drops, glucose soars past 250 mg/dL, and the body starts burning fat for fuel-producing toxic ketones. EDKA looks different. Blood sugar stays below 250 mg/dL, often between 100 and 200 mg/dL. That’s not dangerous on its own. But ketones? They’re climbing. Acid levels? They’re spiking. pH drops below 7.3. Bicarbonate falls under 18 mEq/L. And the patient is in full-blown metabolic crisis.

This wasn’t well understood until 2015. That’s when doctors in the U.S. started seeing patients with vomiting, abdominal pain, and trouble breathing-but their glucose readings were normal. At first, they thought it was food poisoning or a stomach bug. Then they checked ketones. The results shocked them. All had severe ketoacidosis. All were on SGLT2 inhibitors. The FDA issued a safety alert within months. By 2023, EDKA made up 41% of all DKA cases linked to these drugs, up from just 28% in 2015. Why? Because awareness is growing. But many still don’t test for ketones unless glucose is high. That’s the trap.

Why Do SGLT2 Inhibitors Cause This?

SGLT2 inhibitors work by making the kidneys flush out extra glucose through urine. That lowers blood sugar. But here’s the twist: that same action tricks the body into thinking it’s starving. Even if you’re eating normally, your body sees less glucose in the bloodstream and ramps up glucagon-the hormone that tells your liver to make more sugar and your fat cells to break down fat into ketones.

Studies show this isn’t just about low insulin. It’s about the ratio of glucagon to insulin. SGLT2 inhibitors increase glucagon, even in people with type 2 diabetes who still make some insulin. That imbalance is what drives fat breakdown and ketone production. At the same time, these drugs cause mild dehydration and reduce the liver’s ability to make new glucose. So you get a perfect storm: ketones rise, glucose stays normal, and the body has no backup plan.

It’s not just people with type 1 diabetes. About 20% of EDKA cases happen in people with type 2 diabetes who’ve never had DKA before. Off-label use in type 1 patients is common-around 8% of them are on these drugs-and their DKA risk jumps to 5-12%. That’s why the American Association of Clinical Endocrinology now warns against starting SGLT2 inhibitors in anyone with a history of DKA.

How Do You Know If You’re Having It?

Symptoms are almost identical to regular DKA. Nausea? 85% of cases. Vomiting? 78%. Abdominal pain? 65%. Fatigue? 76%. Trouble breathing? 62%. Some people feel like they’re coming down with the flu. Others think they’ve eaten something bad. The biggest red flag? No high blood sugar.

That’s the problem. If your meter reads 180 mg/dL, you might think, “I’m fine.” But your blood is acidic. Your organs are under stress. Your kidneys are working overtime to flush out ketones and glucose. Your brain is being poisoned by acetone and beta-hydroxybutyrate. And if you don’t act, you could slip into coma or cardiac arrest.

There’s no reliable smell test. The classic “fruity breath” of DKA is often missing in EDKA because ketone levels are lower, but still toxic. Don’t wait for a smell. Don’t wait for a spike. If you’re on an SGLT2 inhibitor and you feel unwell, test for ketones-right now.

What Tests Confirm It?

You need three things:

• Blood glucose under 250 mg/dL (often 100-200 mg/dL)
• Metabolic acidosis-confirmed by arterial blood gas showing pH below 7.3 and bicarbonate under 18 mEq/L
• Elevated ketones-serum beta-hydroxybutyrate above 3 mmol/L is diagnostic

Point-of-care ketone meters (like the Precision Xtra or Nova StatStrip) are now standard in emergency departments. Hospitals like the Cleveland Clinic require ketone testing within 15 minutes of triage for any diabetic on an SGLT2 inhibitor with nausea or vomiting. If you’re in an ER and they don’t test your ketones, ask for it. Say: “I’m on an SGLT2 inhibitor. I need a serum beta-hydroxybutyrate test.”

Don’t rely on urine ketone strips. They’re slow, inaccurate, and can miss early or mild cases. Blood ketones are the gold standard.

How Is It Treated in the Emergency Room?

Treatment follows the same basic plan as regular DKA-but with critical adjustments.

1. Fluids first-0.9% saline at 15-20 mL/kg in the first hour. This fixes dehydration and helps flush ketones.
2. Insulin drip-0.1 units/kg/hour. But here’s the key: you can’t wait for glucose to drop before adding sugar. In EDKA, glucose drops fast. So once it hits 200 mg/dL, switch to 5% dextrose in saline. This prevents dangerous hypoglycemia while still letting insulin work on ketones.
3. Potassium replacement-65% of patients have low total body potassium even if their blood level looks normal. You’ll need IV potassium, often 20-40 mEq per liter of fluid, monitored closely.
4. Monitor for lactic acidosis-some patients have mixed acidosis. Lactate levels must be checked to rule out other causes like sepsis or shock.

The goal isn’t just to fix the numbers. It’s to stop the ketone production and restore your body’s pH balance. That takes hours. Most patients stay in the hospital for 24-48 hours.

How to Prevent It

Prevention is simple-but often ignored.

• Stop your SGLT2 inhibitor during illness-if you have the flu, an infection, surgery, or even severe vomiting, stop the drug. Don’t wait for symptoms. Don’t assume it’s “just a bug.”
• Don’t skip carbs-low-carb diets, fasting, or dieting while on these drugs increases risk. Your body needs fuel. Ketones aren’t a safe backup.
• Check ketones during stress-even if your glucose is normal. Keep ketone strips or a meter at home. Test if you feel off.
• Know your warning signs-nausea, vomiting, abdominal pain, fatigue, trouble breathing. These aren’t “just symptoms.” They’re alarms.
• Talk to your doctor-if you have type 1 diabetes, ask if SGLT2 inhibitors are right for you. If you’ve had DKA before, they’re not recommended.

The FDA now requires all SGLT2 inhibitor packaging to include this warning: “Stop taking this medication and seek immediate medical attention if you have symptoms of ketoacidosis, even if your blood sugar is normal.” That’s not fine print. That’s a life-saving instruction.

What’s Changing Now?

Doctors are catching on. Since 2015, overall DKA cases linked to SGLT2 inhibitors have dropped by 32%. But EDKA is now the majority-41% of all cases. That means we’re getting better at spotting it. But we’re not done.

New research is looking at early warning signs. A 2023 study found that a high ratio of acetoacetate to beta-hydroxybutyrate in the blood can predict EDKA 24 hours before symptoms start. Another study is testing whether combining HbA1c variability with C-peptide levels can identify high-risk patients with 82% accuracy.

But none of that matters if you don’t act. The biggest killer isn’t the drug. It’s the belief that “no high blood sugar means no DKA.” That’s outdated. That’s dangerous. That’s how people die.

Bottom Line

If you’re on an SGLT2 inhibitor, you’re not just managing diabetes. You’re managing a hidden risk. This isn’t about avoiding the drug. It’s about using it safely. Test your ketones when you’re sick. Stop the drug during illness. Don’t wait for your glucose to spike. Your life doesn’t depend on your meter. It depends on your awareness.

If you’re a healthcare provider: don’t assume normal glucose means safe. Test ketones. Always. In every diabetic on SGLT2 inhibitors with nausea, vomiting, or unexplained fatigue. That’s not extra work. That’s standard care now.

This condition is preventable. But only if you know what to look for-and act before it’s too late.