What are the next steps for a diabetic patient on Invokana (canagliflozin) with a 5-day history of nausea, stomach pain, dizziness, low oral intake, and fatigue?

Immediate Management of Suspected Diabetic Ketoacidosis in a Patient on Invokana

This patient requires immediate evaluation for diabetic ketoacidosis (DKA), which is a life-threatening emergency—stop Invokana immediately and send the patient to the emergency department now for urgent assessment, as SGLT2 inhibitors like canagliflozin significantly increase the risk of euglycemic DKA where blood glucose may be deceptively normal or only mildly elevated. 1, 2, 3

Why This Is a Medical Emergency

The constellation of symptoms—nausea, vomiting, abdominal pain, fatigue, dizziness, and poor oral intake over 5 days in a diabetic patient on canagliflozin—represents a classic presentation of DKA that requires immediate action. 4, 2

Critical Features Making This High-Risk:

• SGLT2 inhibitor use (Invokana): The FDA explicitly warns that canagliflozin causes ketoacidosis that can be life-threatening, and this can occur even with blood glucose less than 250 mg/dL (termed "euglycemic DKA"). 3
• Unable to maintain oral intake: The 5-day history of nausea and low oral intake means this patient likely cannot tolerate oral hydration, which is an absolute indication for emergency department evaluation. 2
• Prolonged symptom duration: DKA typically develops over hours to days, and this patient has had symptoms for 5 days, suggesting either established DKA or impending hyperglycemic crisis. 4, 2
• Volume depletion: Dizziness suggests orthostatic hypotension from dehydration, a known complication of both DKA and SGLT2 inhibitors. 3

Immediate Actions Required

Before Transport to ED:

1. Check blood glucose and ketones immediately (blood or urine)—assume DKA until proven otherwise, as this is a life-threatening emergency. 1
2. Stop Invokana immediately—the American College of Clinical Endocrinologists recommends discontinuing SGLT2 inhibitors immediately if DKA is suspected, as these drugs significantly increase the risk. 1
3. Do NOT assume normal glucose rules out DKA—patients on SGLT2 inhibitors can develop euglycemic DKA with glucose levels sometimes below 200 mg/dL. 1, 2, 3

Criteria Mandating ER Referral (This Patient Meets Multiple):

• Unable to tolerate oral hydration (5 days of nausea and low oral intake). 2
• Signs of worsening illness (5-day progressive course with fatigue and dizziness). 2
• On SGLT2 inhibitor (high risk for euglycemic DKA requiring lower threshold for evaluation). 2
• Persistent vomiting and abdominal pain (classic DKA presentation). 4, 2

What to Expect in the Emergency Department

The American Diabetes Association and American College of Clinical Endocrinologists recommend the following workup and management: 1

Initial Assessment:

• Blood glucose level, serum or urine ketones, mental status, hydration status, and vital signs. 1
• Electrolytes, blood gases, and metabolic panel every 2-4 hours. 1
• Expected findings in DKA: blood glucose >250 mg/dL (but may be lower with SGLT2 inhibitors), elevated ketones, metabolic acidosis. 1

Treatment Protocol:

• ICU admission if DKA is confirmed or strongly suspected for close monitoring and aggressive treatment. 1
• Isotonic saline (0.9% NaCl) intravenously to restore intravascular volume. 1
• Continuous IV insulin infusion at 0.1 units/kg/hour with target glucose 140-180 mg/dL. 1
• Potassium replacement as soon as urine output is established. 1
• Switch to 5% dextrose with 0.45-0.75% NaCl once blood glucose reaches 250 mg/dL to prevent hypoglycemia while continuing insulin. 1

Critical Pitfalls to Avoid

Do Not Delay Treatment:

• Never assume normal or mildly elevated glucose rules out DKA in patients on SGLT2 inhibitors—euglycemic DKA is well-documented with canagliflozin, with cases reported at glucose levels of 259 mg/dL or even lower. 5, 6
• Do not wait for ketone results if clinical suspicion is high based on symptoms—start treatment immediately. 1
• Do not attribute all symptoms to gastroparesis without first excluding DKA, as vomiting with ketosis is a medical emergency. 1

Special Consideration for SGLT2 Inhibitors:

• Even after discontinuing canagliflozin, glucosuria may persist for more than 10 days, requiring continued monitoring for dehydration and electrolyte abnormalities. 5
• The drug's mechanism causes ongoing urinary glucose loss that can perpetuate volume depletion. 5

Long-Term Management After Resolution

Once DKA is treated and the patient is stabilized:

• Do not restart canagliflozin—this patient has demonstrated intolerance with a serious adverse event. 3
• Consider alternative diabetes medications that do not carry DKA risk. 4
• Educate the patient on DKA warning signs and the importance of checking ketones during illness. 4, 2
• Ensure the patient understands to never stop insulin during illness (if on insulin), as this is the most common cause of preventable DKA. 2

If Gastroparesis Is Later Considered:

Only after DKA is excluded should gastroparesis be considered as a differential diagnosis for the chronic nausea and vomiting, as acute hyperglycemia directly impairs gastric motility in diabetic patients. 1, 7, 8