How to manage diabetes in a patient with osteomyelitis, possible diabetic ketoacidosis, and impaired renal function on Jardiance (Empagliflozin) and Metformin?

Immediate Management: Discontinue Both Jardiance and Metformin Now

This patient has euglycemic diabetic ketoacidosis (DKA) with severe metabolic acidosis (anion gap 26, bicarbonate 8) and must have both Jardiance (empagliflozin) and metformin immediately discontinued, with transition to intravenous insulin therapy. 1, 2

Critical Assessment and Immediate Actions

Confirm Euglycemic DKA Diagnosis

• This presentation is classic for SGLT2 inhibitor-induced euglycemic DKA: severe metabolic acidosis (bicarbonate 8, anion gap 26) in a hospitalized patient on Jardiance with acute illness (osteomyelitis) 1, 3
• Check serum and urine ketones immediately to confirm ketoacidosis 2
• The combination of acute infection, possible reduced oral intake, and continued SGLT2 inhibitor use creates the perfect storm for this life-threatening complication 1, 4, 5

Discontinue Jardiance Immediately

• Jardiance is absolutely contraindicated in this clinical scenario and must be stopped immediately 1
• The FDA label explicitly warns to "assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue JARDIANCE" 1
• SGLT2 inhibitors can cause persistent glucosuria and ketonuria for up to 11 days after discontinuation, potentially leading to relapse of DKA 4
• Do not restart Jardiance during this hospitalization or until the acute illness has completely resolved 1, 5

Discontinue Metformin Immediately

• Metformin must be stopped due to severe metabolic acidosis and risk of lactic acidosis 2
• With bicarbonate of 8 and acute infection (osteomyelitis), this patient has multiple risk factors for metformin-associated lactic acidosis: anaerobic metabolism from infection, severe acidosis, and potential volume depletion 2
• Although creatinine is 0.91 (eGFR likely >60), metformin should be discontinued in patients at risk for lactic acidosis including those with acute kidney injury, hypoxia, or shock 2, 6
• Check serum lactate level to rule out concurrent lactic acidosis 2

Acute Diabetes Management Protocol

Initiate DKA Treatment Protocol

• Start intravenous insulin infusion immediately targeting blood glucose 140-180 mg/dL (7.8-10 mmol/L) 2
• Aggressive intravenous fluid resuscitation is critical for both DKA and potential volume depletion from SGLT2 inhibitor use 1, 3, 5
• Monitor for electrolyte abnormalities, particularly hypokalemia and hypernatremia, which can accompany SGLT2 inhibitor-associated DKA 5
• Continue DKA protocol until anion gap normalizes and bicarbonate >15 mEq/L 3, 4

Monitor for DKA Relapse

• Be vigilant for DKA recurrence even after initial resolution, as SGLT2 inhibitors can cause persistent glucosuria and ketonuria for days after discontinuation 4
• Continue monitoring urine ketones and blood gases for at least 48-72 hours after apparent resolution 4
• One case report documented DKA relapse 8 days after the last dose of dapagliflozin (similar SGLT2 inhibitor) 4

Osteomyelitis Management Considerations

Optimize Glycemic Control for Infection Treatment

• Tight glycemic control is essential for successful osteomyelitis treatment 2, 7, 8
• Poor glycemic control (A1c 8.8%) significantly impairs immune function and wound healing, and can trigger acute exacerbation of chronic osteomyelitis 7
• Target blood glucose 140-180 mg/dL during acute illness to balance infection control with hypoglycemia risk 2

Coordinate with Infectious Disease Team

• Ensure appropriate intravenous antibiotics are continued for osteomyelitis 2
• Duration of antibiotic therapy for osteomyelitis is typically 4-6 weeks, requiring sustained glycemic control throughout treatment 2
• Monitor inflammatory markers (WBC, CRP) and clinical response to antibiotics 2

Transition to Subcutaneous Insulin

When to Transition

• Once DKA resolves (anion gap normalized, bicarbonate >15, ketones cleared) and patient is clinically stable 2
• Patient should be tolerating oral intake before transitioning from IV to subcutaneous insulin 2

Recommended Insulin Regimen

• Initiate basal-bolus insulin regimen with long-acting basal insulin plus rapid-acting insulin before meals 2
• Starting total daily dose: 0.3-0.5 units/kg/day (approximately 23-39 units for this 77 kg patient), given as 50% basal and 50% divided among meals 2
• For patients with poor oral intake or NPO status, use basal-plus approach (basal insulin with correction doses only) to minimize hypoglycemia risk 2

Long-Term Diabetes Management After Discharge

Do Not Restart Jardiance

• Jardiance should be permanently discontinued given this life-threatening complication 1
• The FDA label lists ketoacidosis as a serious risk requiring permanent discontinuation if it occurs 1

Metformin Considerations

• Metformin can be cautiously restarted after hospital discharge once patient is clinically stable, eating normally, and infection is controlled 2, 6
• With baseline creatinine 0.91, no dose adjustment is needed if eGFR remains >60 mL/min/1.73m² 2, 6
• Educate patient on "sick day rules": stop metformin during any serious illness that increases acute kidney injury risk 6

Alternative Oral Agents

• Consider adding a GLP-1 receptor agonist (liraglutide, semaglutide, or dulaglutide) for cardiovascular and glycemic benefits without DKA risk 2
• DPP-4 inhibitors (sitagliptin, linagliptin) are safe alternatives with neutral effect on heart failure risk 2
• Avoid sulfonylureas in hospital setting due to sustained hypoglycemia risk, especially with renal impairment or acute illness 2

Critical Pitfalls to Avoid

• Never assume normal or near-normal glucose excludes DKA in patients on SGLT2 inhibitors - euglycemic DKA is the hallmark complication 1, 3, 4, 5
• Do not restart SGLT2 inhibitors during acute illness, surgery, or periods of reduced oral intake 1, 4, 5
• Do not continue metformin in the setting of severe metabolic acidosis, sepsis, or acute infection 2
• Recognize that SGLT2 inhibitor effects persist for days after discontinuation, requiring prolonged monitoring 4
• Ensure diabetes education includes recognition of DKA symptoms (nausea, vomiting, abdominal pain, dyspnea) and when to seek emergency care 3, 5