SGLT2 Inhibitors and Diabetic Ketoacidosis: What You Need to Know About the Hidden Risk

Most people taking SGLT2 inhibitors for type 2 diabetes don’t think about diabetic ketoacidosis (DKA) until it’s too late. These drugs-like canagliflozin, dapagliflozin, and empagliflozin-help lower blood sugar by flushing glucose out through urine. They’ve been praised for cutting heart failure risk and slowing kidney damage. But behind the benefits is a quiet, dangerous side effect: euglycemic diabetic ketoacidosis. That’s when your body starts burning fat for fuel, flooding your blood with toxic ketones, but your blood sugar stays normal-or barely above normal. And that’s the problem. It doesn’t look like classic DKA. So doctors miss it. Patients ignore it. And sometimes, it kills.

What Is Euglycemic DKA, and Why Is It So Dangerous?

Traditional DKA happens when insulin drops too low, blood sugar spikes above 250 mg/dL, and the body turns to fat for energy. Ketones build up. Blood turns acidic. It’s obvious. You feel sick. You know something’s wrong.

Euglycemic DKA (euDKA) is different. Blood sugar? Often under 200 mg/dL. Sometimes even below 150 mg/dL. You might feel nauseous, tired, or short of breath. Your stomach hurts. You think it’s the flu. Or maybe you’re just stressed. But your body is drowning in ketones. And because your glucose isn’t sky-high, you don’t check your ketones. You don’t go to the ER. You wait it out.

The European Medicines Agency (EMA) confirmed in 2023 that this isn’t rare. About half of all DKA cases linked to SGLT2 inhibitors are euDKA. Studies show patients on these drugs are nearly three times more likely to develop DKA than those on other diabetes pills like DPP-4 inhibitors. The mortality rate? Around 4.3%, higher than traditional DKA, mostly because diagnosis is delayed.

How SGLT2 Inhibitors Trigger Ketone Buildup

SGLT2 inhibitors work by blocking the kidney’s ability to reabsorb glucose. That’s why you pee out extra sugar. But here’s what doesn’t get talked about: they also reduce insulin levels slightly and increase glucagon. That imbalance tricks your body into thinking it’s starving-even if you’re eating normally.

Your liver starts making more glucose. Your fat cells break down faster. Ketones rise. And because your kidneys are already flushing out glucose, they’re also less able to clear ketones. It’s a perfect storm.

This doesn’t happen to everyone. But it happens more often when:

• You’re sick (infection, flu, COVID-19)
• You cut back on carbs (keto diet, fasting, skipping meals)
• You’re having surgery or recovering from it
• You’ve reduced your insulin dose (especially if you have type 1 or advanced type 2 diabetes)
• You drink alcohol heavily

One study found 63% of euDKA cases happened within the first year of starting the drug. The median time to onset? Just 28 weeks. That’s not a long time to be unaware of the risk.

Who’s Most at Risk?

Not everyone on SGLT2 inhibitors is equally vulnerable. Some people are at much higher risk:

• People with low C-peptide levels (under 1.0 ng/mL). This means your pancreas isn’t making much insulin anymore. If you’ve had type 2 diabetes for over 10 years, or you’re losing weight fast, your beta cells may be failing. That’s a red flag.
• Those with type 1 diabetes-even if prescribed off-label. The FDA hasn’t approved SGLT2 inhibitors for type 1, but some doctors still use them. That’s risky without strict ketone monitoring.
• People with a history of DKA. If you’ve had it before, you’re far more likely to get it again.
• Patients on high doses. Canagliflozin 300 mg carries more risk than 100 mg. Higher doses = more glucose loss = more ketone production.
• Those with volume depletion. Dehydration from diuretics, vomiting, or not drinking enough water makes ketones concentrate faster.

A 2016 study found that patients with C-peptide under 1.0 ng/mL had a 2.4% chance of developing DKA on SGLT2 inhibitors. Those with higher levels? Only 0.6%. That’s a four-fold difference.

What Doctors Should Do-And What You Should Ask

The American Diabetes Association, the Endocrine Society, and the EMA all agree: if you’re on an SGLT2 inhibitor, you need to know the signs-and act fast.

Here’s what your doctor should be doing:

• Checking your C-peptide level before prescribing-especially if you’ve had diabetes for more than 5 years.
• Asking if you’ve ever had DKA or ketoacidosis before.
• Explaining the symptoms: nausea, vomiting, abdominal pain, unusual fatigue, trouble breathing, fruity-smelling breath.
• Telling you to stop the drug 3 days before any surgery or hospital procedure.
• Teaching you how to check ketones with urine strips or a blood ketone meter.

And here’s what you should ask your doctor:

• “Is my pancreas still making insulin?”
• “Should I have a ketone meter at home?”
• “What do I do if I feel sick and my blood sugar is normal?”
• “Should I stop this drug before my dental surgery or colonoscopy?”

Real-Life Consequences

A 2023 analysis of FDA reports found 1,247 cases of DKA linked to SGLT2 inhibitors between 2013 and 2022. Nearly half were euDKA. One patient-a 58-year-old man on dapagliflozin-went to the ER with stomach pain and fatigue. His blood sugar? 142 mg/dL. He was told he had gastroenteritis. Two days later, he was in the ICU. His ketones were through the roof. His pH was 7.05. He survived. But he didn’t know he was in danger until it was too late.

Another case: a woman with type 2 diabetes started empagliflozin. She cut carbs to lose weight. Three weeks later, she felt dizzy and nauseous. She didn’t check ketones. She didn’t call her doctor. She passed out at home. She woke up in the hospital. Her ketones were 4.8 mmol/L-life-threatening. Her glucose? 189 mg/dL.

These aren’t outliers. They’re textbook euDKA.

What to Do If You’re on an SGLT2 Inhibitor

If you’re taking one of these drugs, here’s your action plan:

1. Get a ketone meter or test strips. Urine strips work, but blood ketone meters are more accurate. Look for beta-hydroxybutyrate.
2. Check ketones if you’re sick, vomiting, fasting, or feeling unusually tired-even if your blood sugar is normal.
3. Stop the drug 3 days before any surgery or medical procedure.
4. Don’t go on low-carb or keto diets without talking to your doctor first.
5. Drink plenty of water. Dehydration makes ketones worse.
6. If ketones are moderate or high (over 1.5 mmol/L), go to the ER immediately. Don’t wait. Don’t call your doctor first. Go.

A 2022 study showed that when patients were taught how to check ketones and recognize symptoms, DKA cases dropped by 67%. Knowledge saves lives.

Are SGLT2 Inhibitors Still Worth It?

Yes-for most people. The cardiovascular and kidney benefits are real. In the EMPA-REG OUTCOME trial, empagliflozin cut heart-related deaths by 38%. In DECLARE-TIMI 58, dapagliflozin reduced hospitalization for heart failure by 27%. These aren’t small wins.

But benefits don’t erase risk. The absolute risk of DKA is still low-about 0.1 to 0.5 events per 100 patient-years. That’s rare. But when it happens, it’s serious. And it’s preventable.

The key is matching the drug to the person. If you’re young, healthy, with strong insulin production, and you’re not fasting or skipping meals, the risk is minimal. If you’re older, have long-standing diabetes, low C-peptide, or a history of DKA, this drug might not be right for you.

The Future: Safer Drugs and Better Monitoring

Pharmaceutical companies are already working on solutions. One new drug, licogliflozin, blocks both SGLT1 and SGLT2. Early data suggests it might cause fewer ketones because it slows sugar absorption in the gut, reducing the insulin-glucagon imbalance.

The FDA now requires all new SGLT2 inhibitor trials to include specific monitoring for euDKA. Machine learning models are being trained to predict who’s most at risk-using things like age, kidney function, insulin use, and C-peptide levels. One model in 2024 had an accuracy rate of 87%.

But none of that matters if you don’t know the signs.

Final Takeaway

SGLT2 inhibitors are powerful tools. But they’re not harmless. The risk of euDKA is real, silent, and deadly. It doesn’t come with a warning siren. It comes with nausea. Fatigue. A stomachache. A normal blood sugar reading.

If you’re on one of these drugs, don’t wait for a crisis. Talk to your doctor. Get tested. Get educated. Keep ketone strips in your medicine cabinet. Know your body. And if something feels off-even if your glucose is fine-check your ketones. It could save your life.