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

Most people with type 2 diabetes who take SGLT2 inhibitors like Farxiga, Jardiance, or Invokana expect these drugs to lower blood sugar safely. But what if your blood sugar is normal - even low - and you’re still in danger? That’s the hidden risk of euglycemic DKA, a life-threatening condition that doesn’t look like classic diabetic ketoacidosis. It sneaks up when you least expect it, and too many patients end up in the ER because no one thought to check ketones.

What Is Euglycemic DKA?

Euglycemic diabetic ketoacidosis (EDKA) is a form of diabetic ketoacidosis where blood glucose stays below 250 mg/dL - often between 100 and 200 mg/dL - while ketones build up dangerously in the blood. This breaks the old rule that DKA only happens with high blood sugar. In traditional DKA, glucose levels are usually above 300 mg/dL. But with SGLT2 inhibitors, your kidneys are flushing out glucose, so your blood sugar drops even as your body starts burning fat for fuel. That’s when ketones spike.

This isn’t rare. Between 2.6% and 3.2% of all DKA cases in hospitals today are euglycemic. For people taking SGLT2 inhibitors, the risk is seven times higher than for those not on these drugs. Even more alarming: about 20% of EDKA cases happen in people with type 2 diabetes who’ve never had DKA before.

Why Do SGLT2 Inhibitors Cause This?

SGLT2 inhibitors work by blocking glucose reabsorption in the kidneys. That means extra sugar leaves the body through urine - great for lowering blood sugar. But here’s the twist: this triggers a chain reaction. As glucose drops, your pancreas releases more glucagon and less insulin. That imbalance tells your fat cells to break down into free fatty acids, which the liver turns into ketones. At the same time, your liver slows down glucose production because it thinks you’re low on fuel.

So you end up with low glucose but high ketones - a perfect storm for acidosis. It’s like your body thinks it’s starving, even if you just ate. This is why EDKA often happens during illness, fasting, surgery, or even after a night of drinking. Your body’s already under stress, and the drug pushes it over the edge.

How to Spot It - Before It’s Too Late

The symptoms of EDKA are almost identical to regular DKA: nausea, vomiting, abdominal pain, extreme fatigue, trouble breathing, and confusion. But here’s where it gets dangerous - patients and even doctors often dismiss these signs because the glucose meter reads "normal."

One study found that in 13 cases of SGLT2 inhibitor-related EDKA, the average blood sugar was just 180 mg/dL. Many patients were sent home because providers assumed they didn’t have DKA. Some didn’t get treated until they collapsed.

Don’t rely on glucose alone. If you’re on an SGLT2 inhibitor and feel sick, check your ketones - even if your sugar is fine. Use a blood ketone meter if you have one. A level above 3 mmol/L is a red flag. Urine strips can miss early ketosis, so blood testing is better. Don’t wait for fruity breath or rapid breathing - those come later.

Emergency Treatment: What Happens in the ER

If you show up to the ER with nausea, vomiting, and a blood sugar of 160 mg/dL, the first thing they should do is check your ketones and blood pH. An anion gap metabolic acidosis (low bicarbonate, low pH) with elevated ketones confirms EDKA.

Treatment follows similar steps to regular DKA, but with key differences:

1. Fluids first - Start with 0.9% saline at 15-20 mL/kg in the first hour. Dehydration is common, but you can’t overdo it - fluid overload can worsen outcomes.
2. Insulin - Start at 0.1 units/kg/hour. But unlike regular DKA, you need to add glucose to IV fluids early - usually when blood sugar drops below 200 mg/dL. Otherwise, you risk crashing into dangerous hypoglycemia.
3. Potassium - Most patients have normal serum potassium, but their total body potassium is dangerously low. You’ll need aggressive replacement, even if the numbers look okay.
4. Stop the drug - Discontinue the SGLT2 inhibitor immediately. Don’t restart it until you’re fully recovered and the cause of the episode is clear.

Some hospitals now have protocols that require ketone testing within 15 minutes of triage for any diabetic on SGLT2 inhibitors with vomiting or abdominal pain. That’s the standard you should expect.

Who’s at Highest Risk?

Even though SGLT2 inhibitors aren’t approved for type 1 diabetes, about 8% of people with type 1 use them off-label. In this group, DKA rates jump to 5-12%. That’s why experts strongly advise against using these drugs in type 1 patients unless under strict supervision.

Other high-risk situations include:

• Illness (flu, infection, COVID-19)
• Reduced food intake (fasting, dieting, surgery)
• Pregnancy
• Alcohol use
• Recent insulin dose reduction

Even if you’ve been on the drug for years without problems, one of these triggers can flip the switch. That’s why the FDA now requires warning labels that say: "Stop taking this medication and seek medical help immediately if you have symptoms of ketoacidosis, even if your blood sugar is normal."

Prevention: What You Can Do

The best way to avoid EDKA is to know your triggers and act before it starts.

• Check ketones during illness - Don’t wait for high sugar. If you’re sick, nauseous, or vomiting, test ketones twice a day.
• Temporarily stop your SGLT2 inhibitor - When you’re ill, having surgery, or fasting for more than 12 hours, pause the drug. Restart only after you’re eating normally again.
• Keep carbs in your diet - Don’t go low-carb or keto while on these drugs. Your body doesn’t need to burn fat as fuel.
• Carry a medical alert card - If you’re on an SGLT2 inhibitor, wear a bracelet or carry a note saying "On SGLT2 inhibitor - risk of euglycemic DKA."

Some clinics now give patients ketone test strips with their prescription. If yours doesn’t, ask for them. They’re cheap, easy to use, and can save your life.

The Bigger Picture

SGLT2 inhibitors are powerful drugs. They lower blood sugar, protect the heart, and reduce kidney damage in high-risk patients. But they’re not risk-free. The FDA received over 1,000 reports of DKA linked to these drugs between 2015 and 2023. The good news? Awareness has improved. Since 2015, total DKA cases linked to SGLT2 inhibitors have dropped by 32%. But EDKA now makes up 41% of those cases - meaning more people are being diagnosed, but the risk is still there.

Researchers are now testing new tools to predict who’s most at risk. One study found that a high ratio of acetoacetate to beta-hydroxybutyrate in the blood can predict EDKA 24 hours before symptoms start. Another project is combining HbA1c variability and C-peptide levels to spot high-risk patients with 82% accuracy.

But right now, the best predictor is simple: if you’re on an SGLT2 inhibitor and you feel unwell - check your ketones. Don’t wait. Don’t assume your sugar level is safe. That’s the only way to stop this silent killer before it’s too late.