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

Most people think diabetic ketoacidosis (DKA) means high blood sugar. If your glucose is under 250 mg/dL, you’re probably safe-right? Wrong. In patients taking SGLT2 inhibitors like Farxiga, Jardiance, or Invokana, a deadly form of DKA can sneak in with normal or even low blood sugar. This is called euglycemic DKA, and it’s not rare. It’s dangerous, often missed, and can kill if not caught fast.

What Is Euglycemic DKA?

Euglycemic diabetic ketoacidosis (EDKA) is DKA without the high blood sugar you expect. It still has the same deadly triad: low blood pH (below 7.3), low bicarbonate (under 18 mEq/L), and high ketones. But instead of glucose over 300 mg/dL, levels are often between 100 and 250 mg/dL. That’s normal enough to fool even experienced doctors.

This isn’t a myth. It’s real. Since 2015, over 100 documented cases have been reported in the U.S. alone. The FDA issued a boxed warning that same year after 13 cases were found in one study where patients on SGLT2 inhibitors developed DKA with glucose levels below 250 mg/dL. The problem? People assume normal glucose means no DKA. That assumption costs lives.

How Do SGLT2 Inhibitors Cause This?

SGLT2 inhibitors work by making your kidneys dump glucose into your urine. That lowers blood sugar. Sounds good, right? But here’s what happens behind the scenes:

• Your body thinks it’s low on fuel because glucose is being flushed out.
• Your pancreas releases more glucagon-the hormone that tells your liver to make sugar.
• But because SGLT2 inhibitors block glucose reabsorption, that sugar doesn’t stay in your blood.
• Instead, your body starts breaking down fat for energy, producing ketones like beta-hydroxybutyrate.
• Insulin levels stay too low to stop this process, especially if you’re sick, fasting, or stressed.

It’s a perfect storm: low glucose, high ketones, acid buildup. And because your body isn’t getting glucose from food or your blood, you don’t get the usual warning signs of high sugar-like extreme thirst or frequent urination.

Who’s at Risk?

You don’t have to have type 1 diabetes to get EDKA. In fact, most cases happen in people with type 2 diabetes. But here’s the twist: SGLT2 inhibitors aren’t even approved for type 1 patients. Yet, about 8% of people with type 1 diabetes are still prescribed them off-label.

Risk factors include:

• Illness (infections, flu, COVID-19)
• Surgery or trauma
• Pregnancy
• Alcohol use
• Very low-carb diets or fasting
• Skipping meals
• Reduced insulin doses (especially in type 1 patients)

One study found that 20% of EDKA cases happened in people with type 2 diabetes who had never had DKA before. That means even if you’ve been stable for years, you’re not immune.

What Are the Symptoms?

The symptoms look just like regular DKA-or like you’ve got the flu:

• Nausea and vomiting (85% of cases)
• Abdominal pain (65%)
• Deep, fast breathing (Kussmaul respirations)
• Extreme tiredness or weakness (76%)
• Confusion or dizziness
• Fever or chills (often mistaken for infection)

Here’s the trap: you might not smell fruity. That’s the classic DKA sign-acetone breath. But in EDKA, ketone levels can be lower, so the smell isn’t always there. And your glucose? It’s normal. So you think, “I’m fine.” Then you collapse.

Why Is It So Often Missed?

Emergency rooms get hundreds of patients with nausea and vomiting every day. Most are sent home with a diagnosis of gastroenteritis. But if you’re on an SGLT2 inhibitor, that vomiting could be the first sign of metabolic collapse.

A 2015 study in Diabetes Care showed that 13 patients with EDKA were initially misdiagnosed because their glucose levels were “not high enough.” One patient died. Another went into cardiac arrest before ketones were tested.

Doctors aren’t to blame. They’re trained to link DKA with high sugar. But SGLT2 inhibitors changed the rules. Now, normal glucose doesn’t rule out DKA-it makes it more dangerous.

How Is It Diagnosed?

You can’t rely on fingerstick glucose alone. You need three things:

1. Blood pH below 7.3
2. Serum bicarbonate under 18 mEq/L
3. Ketones in blood or urine-specifically beta-hydroxybutyrate above 3 mmol/L

Point-of-care ketone meters (like the Precision Xtra or Nova Max) are essential. Urine ketone strips are too slow and unreliable. They detect acetoacetate, not beta-hydroxybutyrate-the main ketone in EDKA.

Don’t wait for labs. If you’re on an SGLT2 inhibitor and feel sick, test your blood ketones right away. If they’re elevated, go to the ER. Don’t wait for glucose to spike.

Emergency Treatment: What Happens in the Hospital?

Treatment is similar to regular DKA-but with key differences:

• Fluids: Start with 0.9% saline at 15-20 mL/kg in the first hour. Dehydration is severe, even if glucose looks normal.
• Insulin: Start at 0.1 units/kg/hour. But here’s the catch-you can’t wait for glucose to hit 250 mg/dL to add dextrose. In EDKA, glucose drops fast. Add 5% or 10% dextrose when glucose falls below 200 mg/dL to prevent hypoglycemia.
• Potassium: You’re likely low on potassium, even if your blood test looks normal. Replace it early and often. About 65% of EDKA patients have depleted total body potassium.
• Monitoring: Check ketones every 2-4 hours. Don’t stop insulin until ketones are under 0.6 mmol/L and pH is normal.

Many hospitals now have protocols specifically for EDKA. The Cleveland Clinic requires serum ketone testing within 15 minutes for any diabetic on SGLT2 inhibitors who presents with nausea or vomiting.

How to Prevent It

Prevention is easier than treatment:

• Stop your SGLT2 inhibitor during illness. If you have the flu, surgery, or an infection, pause the drug until you’re well. Talk to your doctor about when to restart.
• Never skip meals. Even if you’re trying to lose weight, don’t fast. Your body needs fuel to avoid ketosis.
• Check ketones when you’re sick-even if your glucose is normal. Keep a ketone meter at home. Test if you feel nauseous, tired, or have abdominal pain.
• Don’t use SGLT2 inhibitors if you have a history of DKA. The American Association of Clinical Endocrinology advises against starting them in patients with prior DKA.
• Know the warning signs. If you’re on one of these drugs and feel off, don’t wait for sugar to rise. Test ketones. Call your doctor. Go to the ER.

What’s Changing Now?

Since 2015, awareness has improved. EDKA now makes up 41% of all SGLT2-related DKA cases-up from 28%. That’s because more providers are testing ketones early.

Research is also moving forward. A 2023 study found that a high ratio of acetoacetate to beta-hydroxybutyrate in the blood can predict EDKA 24 hours before symptoms appear. That could lead to early alerts for high-risk patients.

There’s also a national study (NCT04987231) testing a risk score that combines HbA1c variability and C-peptide levels. Early results show it can identify high-risk patients with 82% accuracy.

Final Message

SGLT2 inhibitors are powerful drugs. They help with weight loss, heart health, and kidney protection. But they come with a hidden risk: euglycemic DKA. It doesn’t announce itself with high sugar. It whispers. And if you ignore the whisper, it screams.

If you take Farxiga, Jardiance, or Invokana, you need to know this. Test your ketones when you’re sick. Don’t wait. Don’t assume. Don’t trust your glucose meter alone. Your life might depend on it.