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

Most doctors still think diabetic ketoacidosis (DKA) means high blood sugar. But that’s not always true - especially if the patient is taking an SGLT2 inhibitor. In fact, many patients with this life-threatening condition have blood sugar levels that look almost normal. This is called euglycemic diabetic ketoacidosis, or EDKA. And it’s killing people because it’s being missed.

What Is Euglycemic DKA?

Euglycemic DKA is a form of diabetic ketoacidosis where the body is flooded with ketones and blood is acidic, but blood glucose stays below 250 mg/dL. That’s far below the classic DKA threshold of 300-600 mg/dL. It’s not rare. Studies show it accounts for 2.6% to 3.2% of all DKA hospitalizations. And it’s almost always linked to SGLT2 inhibitors - drugs like dapagliflozin (Farxiga), empagliflozin (Jardiance), and canagliflozin (Invokana).

These drugs were designed to lower blood sugar by making the kidneys flush out glucose through urine. But they also trigger a hidden chain reaction: reduced insulin, increased glucagon, and a breakdown of fat into ketones. The result? Acidosis without the red flag of high glucose. Patients feel terrible - nauseous, tired, breathing hard - but their glucometer says, "You’re fine." That’s the trap.

Why SGLT2 Inhibitors Cause This

SGLT2 inhibitors work by blocking glucose reabsorption in the kidneys. More glucose leaves the body. Blood sugar drops. That sounds good - until it isn’t.

The body sees less glucose and thinks it’s starving. Even if you’re eating normally, your pancreas responds by lowering insulin and raising glucagon. Glucagon tells your liver to make more glucose and your fat cells to break down into fatty acids. Those fatty acids turn into ketones. And because the kidneys are already dumping glucose, there’s no buffer to stop the acid buildup.

It’s a perfect storm: low insulin, high glucagon, volume loss from frequent urination, and ketones piling up. You don’t need to be fasting. You don’t need to skip insulin. You just need to be on the drug and get sick - even a little.

Who’s at Risk?

You might think only type 1 diabetics are at risk. But that’s not true. About 20% of EDKA cases happen in people with type 2 diabetes who’ve never had DKA before. Off-label use of SGLT2 inhibitors in type 1 patients is common - about 8% of them are on these drugs, even though they’re not FDA-approved for that use. And in that group, DKA rates jump to 5-12%.

Risk factors are simple: anything that stresses the body.

• Illness (cold, flu, infection)
• Surgery or trauma
• Pregnancy
• Drinking alcohol
• Going on a very low-carb diet
• Reduced food intake

A patient might be doing fine on their SGLT2 inhibitor - until they get a stomach bug. They stop eating. They drink less. Their blood sugar stays around 180 mg/dL. They feel awful. They assume it’s just the virus. They wait too long. By the time they get to the ER, they’re in metabolic crisis.

How It Presents: The Symptoms

The symptoms of EDKA are identical to classic DKA - and they’re easy to ignore.

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

Some people think a fruity breath means ketones. But in EDKA, ketone levels can be lower, so that smell may be absent. Don’t rely on it.

And here’s the biggest red flag: normal or only mildly elevated blood sugar. If a diabetic on an SGLT2 inhibitor has nausea and a glucose reading of 160 mg/dL, most providers will say, "It’s not DKA." That’s where the mistake happens.

Diagnosis: What Labs to Check

You can’t diagnose EDKA with a glucometer. You need three things:

1. Blood pH below 7.3
2. Serum bicarbonate below 18 mEq/L
3. Ketones in blood or urine - and they must be high

The gold standard is serum beta-hydroxybutyrate. Levels above 3 mmol/L confirm significant ketoacidosis. Urine ketones (dipstick) can miss early cases because they measure acetoacetate, not beta-hydroxybutyrate - the main ketone in EDKA.

Anion gap will be elevated - usually above 12 mEq/L. Lactate might also be high, so you need to rule out sepsis or shock. Leukocytosis is common, but it’s usually from dehydration, not infection.

Emergency Treatment: It’s Different Than You Think

Treating EDKA is like treating classic DKA - but with critical differences.

Fluids first. Start with 0.9% saline at 15-20 mL/kg in the first hour. Then 250-500 mL/hour. But don’t overdo it. Patients are often volume-depleted from frequent urination.

Insulin is needed - but carefully. Give 0.1 units/kg/hour IV. But here’s the catch: because blood sugar is already low, you can’t wait until it hits 200 mg/dL to start glucose-containing fluids. In classic DKA, you hold insulin until glucose drops below 250 mg/dL. In EDKA, you start dextrose (D5W) at the beginning - or very early - to prevent dangerous drops in blood sugar. Some protocols start D5W with insulin from minute one.

Potassium is critical. Even if serum potassium looks normal, total body potassium is often low. About 65% of EDKA patients have hidden potassium depletion. Replace it early and often. Check levels every 2 hours.

Don’t delay ketone testing. At the Cleveland Clinic, any diabetic on an SGLT2 inhibitor with nausea or vomiting gets a serum beta-hydroxybutyrate test within 15 minutes of triage. If it’s over 3 mmol/L, treat as DKA - no matter what the glucose says.

Prevention: What Patients Need to Know

The FDA added a boxed warning to all SGLT2 inhibitor labels in 2015. But many patients still don’t know the risks.

Patients must be told:

• Stop taking your SGLT2 inhibitor if you’re sick, having surgery, or not eating.
• Check your ketones if you feel nauseous, tired, or have stomach pain - even if your blood sugar is normal.
• Don’t wait for your sugar to spike. Ketones can rise fast.
• Keep ketone strips at home. Use a blood ketone meter if possible - they’re more accurate than urine strips.

Doctors should avoid starting SGLT2 inhibitors in patients with a history of DKA. For type 1 diabetics on these drugs, monitor closely. Don’t assume they’re "stable" just because their HbA1c is good.

What’s New in 2025?

Research is catching up. A 2023 study found that a high ratio of acetoacetate to beta-hydroxybutyrate in the blood may predict EDKA 24 hours before symptoms start. That could lead to early alerts.

A new risk-prediction tool is being tested across 15 U.S. hospitals. It combines HbA1c variability with C-peptide levels. Early results show it can spot high-risk patients with 82% accuracy. That’s huge.

And here’s something alarming: since 2015, overall DKA cases on SGLT2 inhibitors have dropped 32% - but EDKA now makes up 41% of all cases. That means more people are surviving because providers are catching it earlier. But the problem isn’t going away. It’s just becoming more visible.

The Bottom Line

SGLT2 inhibitors are powerful drugs. They help with weight, blood pressure, and heart health. But they come with a silent danger: euglycemic DKA. It doesn’t look like DKA. It doesn’t act like DKA. But it kills just the same.

If you’re a provider: Never rule out DKA because blood sugar is normal. If you’re a patient: Check ketones when you’re sick, even if your sugar is fine.

This isn’t about avoiding these drugs. It’s about using them safely. And that means changing how we think - and what we test for - when a diabetic feels unwell.