In a 60-year-old woman on dapagliflozin who presents with euglycemic ketoacidosis, should I use a point‑of‑care serum beta‑hydroxybutyrate (BHB) meter instead of urine ketone strips to assess ketosis?

Use Point-of-Care Serum Beta-Hydroxybutyrate Testing, Not Urine Ketone Strips

In a patient on dapagliflozin presenting with suspected euglycemic ketoacidosis, you should use point-of-care serum beta-hydroxybutyrate (BHB) measurement instead of urine ketone strips for accurate assessment and monitoring of ketosis. 1, 2

Why Serum BHB is Superior to Urine Ketones

Biochemical and Clinical Accuracy

• Serum BHB directly measures the predominant ketone body produced during ketotic states, whereas urine ketone strips only detect acetoacetate and acetone—they do not detect BHB at all. 1, 3
• Blood BHB testing shows greater sensitivity and specificity than urine ketones for assessing diabetic ketoacidosis (DKA). 3, 4
• In a quaternary care system analysis, 24% of contemporaneously ordered BHB and urine ketone tests were discordant, with the majority showing elevated BHB concentrations alongside normal urine ketone results—meaning urine testing would have missed clinically significant ketosis. 3

Specific Advantages in SGLT2-Inhibitor-Associated Ketoacidosis

• The FDA label for dapagliflozin explicitly states that ketoacidosis can occur even with blood sugar less than 250 mg/dL (euglycemic DKA), and recommends checking ketones in urine or blood when symptoms arise. 2
• Urine ketone testing is particularly unreliable in patients with impaired kidney function, which is common in those taking SGLT2 inhibitors and may be further compromised during volume depletion or acute illness. 3
• SGLT2 inhibitors like dapagliflozin decrease renal excretion of beta-hydroxybutyrate and acetoacetate, making urine ketone measurements even less reliable in this population. 5

Clinical Outcomes and Guideline Support

Evidence for Improved Patient Outcomes

• Blood BHB testing compared to urine testing is associated with reduced frequency of hospitalization, reduced time to recovery from DKA, cost benefits, and greater patient satisfaction. 4
• Point-of-care BHB devices simplify the diagnostic approach to hyperglycemic and euglycemic patients, allowing for more rapid treatment decisions. 6
• Current professional guidelines recommend BHB testing over urine ketones for assessing DKA. 3

Monitoring Requirements for Dapagliflozin Patients

• The FDA warns that patients on dapagliflozin may be asked by their healthcare provider to periodically check ketones in urine or blood, but blood testing is preferred for accuracy. 2
• Patients at risk for euglycemic DKA when treated with SGLT2 inhibitors should be advised to monitor blood ketone levels on a regular basis, as they are not alerted to incipient DKA by glucose testing alone. 5
• Regular blood ketone testing is recommended because patients are not alerted to incipient DKA by glucose testing alone in euglycemic ketoacidosis. 5

Common Pitfalls and How to Avoid Them

False Results with Urine Testing

• Highly colored urine can cause false-positive results on urine ketone dipstick tests. 1
• Sulfhydryl-containing drugs such as captopril can generate false-positive ketone readings on nitroprusside-based urine tests. 1
• Prolonged exposure of ketone test strips to air or highly acidic urine (e.g., after large vitamin C intake) may lead to false-negative ketone results. 1

Delayed Recognition of Euglycemic DKA

• Be aware that glucosuria and ketonuria can persist for days after stopping dapagliflozin, even when serum glucose normalizes—one case report documented relapse of euglycemic DKA eight days after the last dose of dapagliflozin. 7
• Euglycemic ketoacidosis can occur in non-diabetic patients on SGLT2 inhibitors, particularly during fasting, stress, or reduced food intake. 8

Practical Implementation

When to Check Serum BHB in This Patient

• Immediately upon presentation with symptoms of nausea, vomiting, abdominal pain, tiredness, or trouble breathing—even if blood glucose is normal or near-normal. 2
• During treatment monitoring to assess response to therapy and guide decisions about resolution of ketoacidosis. 9, 4
• Consider checking if the patient has reduced food or liquid intake, volume depletion, concurrent illness, or recent surgery—all risk factors for SGLT2-inhibitor-associated ketoacidosis. 2

Treatment Considerations

• Discontinue dapagliflozin immediately if ketoacidosis is confirmed. 2
• Standard DKA protocols apply, though insulin requirements may differ in euglycemic presentations—intravenous dextrose with bicarbonate may be sufficient in some cases without insulin. 8
• Monitor for resolution of ketoacidosis before considering restarting any SGLT2 inhibitor therapy. 2