What is the management for a diabetic adult on Ozempic (semaglutide) and Jardiance (empagliflozin) presenting with 4 days of diarrhea, dehydration, leukocytosis, and metabolic acidosis with a serum pH of 7.23 and elevated lactate levels?

Management of Diabetic Patient with Diarrhea, Dehydration, and Metabolic Acidosis on SGLT2 Inhibitor

Immediately discontinue Jardiance (empagliflozin) and initiate aggressive fluid resuscitation with isotonic saline while evaluating for SGLT2 inhibitor-induced euglycemic or ketotic diabetic ketoacidosis (DKA), as this drug class causes volume depletion and can precipitate life-threatening ketoacidosis even with normal glucose levels. 1, 2

Immediate Actions

Discontinue SGLT2 Inhibitor

• Stop Jardiance immediately - the FDA label explicitly warns that empagliflozin causes intravascular volume contraction and can precipitate ketoacidosis in settings of reduced oral intake or fluid losses (such as gastrointestinal illness), which directly applies to this patient with 4 days of diarrhea 1
• SGLT2 inhibitors are known to cause euglycemic DKA where blood glucose may be less than 250 mg/dL, making the diagnosis easily missed 1, 2
• The combination of dehydration from diarrhea and SGLT2 inhibitor use creates a perfect storm for metabolic decompensation 1, 3

Assess for Ketoacidosis

• Check serum and urine ketones immediately regardless of glucose level, as SGLT2 inhibitor-associated ketoacidosis can present with euglycemia 1, 2
• With pH 7.23 and lactate 3, determine if this is pure lactic acidosis, ketoacidosis, or mixed 4, 5
• Calculate anion gap: (Na) - (Cl + HCO3) to characterize the acidosis 6
• Obtain serum bicarbonate level - if <18 mEq/L with positive ketones, this meets DKA criteria even if glucose is not severely elevated 6, 4

Fluid Resuscitation Protocol

Initial Aggressive Hydration

• Administer 0.9% normal saline at 15-20 mL/kg/hour (approximately 1-1.5 L) in the first hour to restore circulatory volume and tissue perfusion 6, 4
• For severe dehydration with signs of shock, increase to 25-30 mL/kg (2-3 L) in the first hour 4
• This addresses both the SGLT2 inhibitor-induced volume depletion and the diarrhea-related losses 1, 4

Subsequent Fluid Management

• After initial resuscitation, continue isotonic saline at lower rates based on hydration status, electrolytes, and urine output 6
• Monitor for signs of volume overload, particularly given the cardiac risks in diabetic patients 7

Electrolyte Management

Potassium Replacement

• Check potassium level immediately and monitor every 2-4 hours - this is critical as hypokalemia can trigger cardiac arrhythmias including atrial flutter 7
• Begin potassium replacement once serum K+ falls below 5.5 mEq/L to prevent life-threatening arrhythmias 7
• Typical deficit in DKA is 3-5 mEq/kg body weight 6
• Add 20-30 mEq potassium to each liter of IV fluid once levels are safe 6

Sodium and Chloride

• Calculate corrected sodium: measured Na + 1.6 × [(glucose - 100)/100] to guide therapy 4
• Typical sodium deficit is 7-10 mEq/kg in DKA 6

Insulin Therapy Decision Tree

If Ketoacidosis is Present (positive ketones, bicarbonate <18 mEq/L)

• Start continuous IV regular insulin at 0.1 units/kg/hour after initial fluid bolus 4, 6
• Do NOT give insulin bolus if patient is significantly hypovolemic - correct volume first 6
• When glucose reaches 250-300 mg/dL, add dextrose 5-10% to IV fluids and reduce insulin to 0.05-0.1 units/kg/hour 4
• Continue insulin infusion until pH >7.30, bicarbonate >18 mEq/L, and anion gap normalizes 6

If Pure Lactic Acidosis (negative ketones, elevated lactate)

• Focus on treating underlying cause and volume resuscitation 5
• Insulin may not be primary therapy unless glucose is significantly elevated 5

Bicarbonate Therapy

Do NOT administer bicarbonate - the American Diabetes Association clearly states bicarbonate does not improve resolution of acidosis or clinical outcomes in DKA, regardless of pH level 4, 8, 6

• Even with pH 7.23, bicarbonate therapy has shown no benefit and may cause harm 4, 6
• The only potential exception is pH <6.9 in pediatric patients, which does not apply here 6

Infection Workup and Treatment

Evaluate for Infectious Diarrhea

• Obtain stool cultures, Clostridioides difficile testing, and stool white blood cells given 4-day duration and leukocytosis 6
• Blood cultures should be drawn given elevated WBC and potential for sepsis 6, 4
• Urinalysis and urine culture to evaluate for urinary tract infection as precipitant 6, 4

Antibiotic Therapy

• If infection is identified, initiate broad-spectrum IV antibiotics such as ceftriaxone or piperacillin-tazobactam 4
• Treat the underlying infection aggressively as this is likely the precipitating factor for metabolic decompensation 6, 4

Monitoring Protocol

Laboratory Monitoring

• Check blood glucose, electrolytes, venous pH, and anion gap every 2-4 hours until acidosis resolves 6
• Venous pH is adequate for monitoring - repeat arterial blood gases are unnecessary 6
• Monitor serum creatinine and BUN for acute kidney injury, which is common with SGLT2 inhibitors in volume-depleted states 1

Cardiac Monitoring

• Continuous cardiac monitoring is essential given pH <7.3, potential electrolyte abnormalities, and risk of arrhythmias 7
• Watch specifically for signs of hypokalemia-induced arrhythmias 7

Critical Pitfalls to Avoid

SGLT2 Inhibitor-Specific Risks

• Never restart Jardiance during acute illness with reduced oral intake - the FDA label specifically warns against use in settings of gastrointestinal illness or fluid losses 1
• Recognize that euglycemic DKA can occur with glucose <250 mg/dL, making diagnosis challenging 1, 2
• The combination of SGLT2 inhibitor plus volume depletion from diarrhea creates synergistic risk for acute kidney injury requiring dialysis 1, 3

Insulin Transition

• When transitioning from IV to subcutaneous insulin, administer basal insulin 2-4 hours before stopping IV insulin to prevent rebound hyperglycemia and recurrent ketoacidosis 6, 4
• Abrupt discontinuation of IV insulin without adequate subcutaneous coverage leads to metabolic decompensation 6

Ozempic Considerations

• Temporarily hold semaglutide (Ozempic) during acute illness as GLP-1 agonists can worsen nausea and reduce oral intake 1
• GLP-1 agonists may contribute to dehydration through gastrointestinal side effects 9

Resolution Criteria

DKA is resolved when ALL of the following are met 6:

• Glucose <200 mg/dL
• Serum bicarbonate ≥18 mEq/L
• Venous pH ≥7.30
• Anion gap normalized

Once resolved, transition to subcutaneous insulin regimen with appropriate overlap as described above 6, 4.