From the Guidelines
SGLT2 inhibitors can precipitate Diabetic Ketoacidosis (DKA) in patients with diabetes, particularly those with type 1 diabetes or insulin-deficient type 2 diabetes, with a risk that can be 5–17 times higher than that in people with type 1 diabetes not treated with SGLT inhibitors 1. The risk of DKA associated with SGLT2 inhibitors is a significant concern, especially in certain patient populations. Key factors that increase the risk of DKA in individuals treated with SGLT inhibitors include:
- Very-low-carbohydrate diets
- Prolonged fasting
- Dehydration
- Excessive alcohol intake
- Other common precipitating factors, such as acute illness or surgical stress 1. It is essential to note that SGLT2 inhibitors are not approved for use in people with type 1 diabetes, and individuals who have experienced DKA should not be treated with SGLT inhibition 1. Patients taking SGLT2 inhibitors should be educated about the signs and symptoms of DKA, including nausea, vomiting, abdominal pain, fatigue, and rapid breathing, and advised to temporarily discontinue the medication during acute illness or planned surgical procedures. Additionally, DKA associated with SGLT2 inhibitors may present atypically with only mildly elevated blood glucose levels (euglycemic DKA), making diagnosis challenging 1.
From the FDA Drug Label
Metabolism and Nutrition Disorders: Ketoacidosis The diabetes medication that can precipitate Diabetic Ketoacidosis (DKA) is dapagliflozin 2.
- Key points:
- Dapagliflozin can cause ketoacidosis, a serious condition that requires immediate medical attention.
- The risk of ketoacidosis may be increased with concomitant use of certain medications, such as carbonic anhydrase inhibitors.
- Patients should be closely monitored for signs and symptoms of ketoacidosis, such as nausea, vomiting, abdominal pain, and rapid breathing.
From the Research
Diabetes Medications that can Precipitate DKA
- SGLT2 inhibitors, such as dapagliflozin 3, 4, 5, 6 and canagliflozin 7, have been associated with an increased risk of developing diabetic ketoacidosis (DKA)
- These medications can cause euglycemic DKA, which is a condition where the blood glucose levels are not elevated, but the body still produces ketones 3, 7, 6
- The risk of DKA is higher in patients with insulin-deficient diabetes, including those with type 2 diabetes, and is typically precipitated by factors such as insulin omission or dose reduction, severe acute illness, dehydration, extensive exercise, surgery, low-carbohydrate diets, or excessive alcohol intake 4, 5
Precipitating Factors for DKA
- Insulin omission or dose reduction 4, 5
- Severe acute illness 4, 5, 6
- Dehydration 4, 5
- Extensive exercise 4, 5
- Surgery 4, 5
- Low-carbohydrate diets 4, 5
- Excessive alcohol intake 4, 5
- Acute illnesses such as diffuse paralytic ileus and urinary tract infection 6
- Dietary restrictions or fasting in patients with diabetes 6
Prevention and Diagnosis of DKA
- Withholding SGLT2 inhibitors when precipitants develop 5
- Avoiding insulin omission or inappropriate insulin dose reduction 5
- Following sick day protocols as recommended 5
- Suspecting DKA in patients presenting with signs or symptoms, especially euglycemic patients 5
- Investigating for DKA and stopping SGLT2 inhibitor treatment if diagnosed 5