Over a span of several months, I helped care for three separate patients taking sodium-glucose cotransporter-2 (SGLT2) inhibitors for at least the past 2 years who presented to the ICU with euglycemic diabetic ketoacidosis (DKA) within a few weeks of initiating a keto diet.
These days, SGLT2 inhibitors are being prescribed so frequently, it sometimes feels like they’ve been added to the water supply. Yet, most of us can agree that they aren’t always safe, and several US Food and Drug Administration (FDA) warnings have been added or strengthened for [acute kidney injury], [urinary tract infection], and euglycemic DKA.
The FDA warning on euglycemic DKA focuses on pausing SGLT2 inhibitors for several days prior to surgery and asks patient to tell their healthcare professional about any of the following DKA risk factors prior to taking an SGLT2 inhibitor: eating less due to illness, a history of pancreatitis, or frequent or binge alcohol consumption. There is no mention of a keto diet. However, the mechanisms of action of SGLT2 inhibitors and that of a keto diet are synergistic in nature, propelling the body rapidly into a DKA. Unfortunately, most of us were not taught this about this drug class.
Within the confines of the disorganized healthcare system in the United States, the silos in which each healthcare profession works further hamper our ability to provide safe care to our patients with diabetes initiated on SGLT2 inhibitors.
In pharmacy school, we are not taught that “avoiding a keto diet” is a key counseling point to touch on when a patient first picks up their empagliflozin. Dietary considerations are lost in a sea of existing warnings that take priority. And dietitians are not taught to screen med lists for SGLT2 inhibitors when patients come to see them about starting a keto diet.
It’s also unclear if clinicians ask about a patient’s dietary habits, particularly the keto diet, prior to prescribing one of these agents. I verbally surveyed my favorite cardiologists to ask what they educate the patient on when initially prescribing these drugs. The most enthusiastic response I received was: “I just tell them it’s a wonder drug. That’s all I have time for.” Time constrained by a rapid fire 15-minute visit, counseling points are likely not at the forefront of the specialist’s mind.
If we expect that pharmacists are counseling all patients on all new drugs — as I believe they should — we’d be sorely wrong. Pharmacists are counseling fewer patients over time, while the popularity of the keto diet is burgeoning (it was the most searched for diet on Google in 2020 at over 25 million searches).
With the internet and AI at their fingertips, a patient could easily decide to start a keto diet on a whim without mentioning it to their pharmacist, primary care provider, or endocrinologist. This was the case for the three euglycemic DKA patients I saw in the ICU in short succession. The fact that in all of these instances the patient had previously tolerated an SGLT2 inhibitor for at least 2 years seems to highlight the sudden risk of the addition of the keto diet to their otherwise stable pharmacotherapy.
Cases of euglycemic DKA with concomitant SGLT2 inhibitor use and keto diet should be reported to the FDA through the MedWatch website so as to better capture the nationwide incidence of this safety issue. But for now, should we counsel patients who get started on an SGLT2 inhibitor not to initiate a keto diet? My intuition says that would be the safest choice to avoid unwarranted ICU admissions, but hopefully time will tell.
The silver lining of all this is that, from first-hand experience, I can confirm that attempting to adhere to a keto diet is nearly impossible. Otherwise, I suspect this concern would be cropping up left and right.
COMMENTARY
Keto Diet With SGLT2 Inhibitors May Contribute to Diabetic Ketoacidosis
DISCLOSURES
| April 10, 2025Over a span of several months, I helped care for three separate patients taking sodium-glucose cotransporter-2 (SGLT2) inhibitors for at least the past 2 years who presented to the ICU with euglycemic diabetic ketoacidosis (DKA) within a few weeks of initiating a keto diet.
These days, SGLT2 inhibitors are being prescribed so frequently, it sometimes feels like they’ve been added to the water supply. Yet, most of us can agree that they aren’t always safe, and several US Food and Drug Administration (FDA) warnings have been added or strengthened for [acute kidney injury], [urinary tract infection], and euglycemic DKA.
The FDA warning on euglycemic DKA focuses on pausing SGLT2 inhibitors for several days prior to surgery and asks patient to tell their healthcare professional about any of the following DKA risk factors prior to taking an SGLT2 inhibitor: eating less due to illness, a history of pancreatitis, or frequent or binge alcohol consumption. There is no mention of a keto diet. However, the mechanisms of action of SGLT2 inhibitors and that of a keto diet are synergistic in nature, propelling the body rapidly into a DKA. Unfortunately, most of us were not taught this about this drug class.
Within the confines of the disorganized healthcare system in the United States, the silos in which each healthcare profession works further hamper our ability to provide safe care to our patients with diabetes initiated on SGLT2 inhibitors.
In pharmacy school, we are not taught that “avoiding a keto diet” is a key counseling point to touch on when a patient first picks up their empagliflozin. Dietary considerations are lost in a sea of existing warnings that take priority. And dietitians are not taught to screen med lists for SGLT2 inhibitors when patients come to see them about starting a keto diet.
It’s also unclear if clinicians ask about a patient’s dietary habits, particularly the keto diet, prior to prescribing one of these agents. I verbally surveyed my favorite cardiologists to ask what they educate the patient on when initially prescribing these drugs. The most enthusiastic response I received was: “I just tell them it’s a wonder drug. That’s all I have time for.” Time constrained by a rapid fire 15-minute visit, counseling points are likely not at the forefront of the specialist’s mind.
If we expect that pharmacists are counseling all patients on all new drugs — as I believe they should — we’d be sorely wrong. Pharmacists are counseling fewer patients over time, while the popularity of the keto diet is burgeoning (it was the most searched for diet on Google in 2020 at over 25 million searches).
With the internet and AI at their fingertips, a patient could easily decide to start a keto diet on a whim without mentioning it to their pharmacist, primary care provider, or endocrinologist. This was the case for the three euglycemic DKA patients I saw in the ICU in short succession. The fact that in all of these instances the patient had previously tolerated an SGLT2 inhibitor for at least 2 years seems to highlight the sudden risk of the addition of the keto diet to their otherwise stable pharmacotherapy.
Cases of euglycemic DKA with concomitant SGLT2 inhibitor use and keto diet should be reported to the FDA through the MedWatch website so as to better capture the nationwide incidence of this safety issue. But for now, should we counsel patients who get started on an SGLT2 inhibitor not to initiate a keto diet? My intuition says that would be the safest choice to avoid unwarranted ICU admissions, but hopefully time will tell.
The silver lining of all this is that, from first-hand experience, I can confirm that attempting to adhere to a keto diet is nearly impossible. Otherwise, I suspect this concern would be cropping up left and right.
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
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