What is the diagnosis for a patient with severe hyperglycemia, impaired renal function, and signs of dehydration, on empagliflozin (SGLT2 inhibitor) and Lantus (insulin glargine)?

Hyperosmolar Hyperglycemic State (HHS)

This patient has hyperosmolar hyperglycemic state (HHS), a life-threatening diabetic emergency characterized by severe hyperglycemia, hyperosmolality, and profound dehydration without significant ketoacidosis, likely precipitated by empagliflozin-induced osmotic diuresis in the setting of inadequate fluid intake. 1

Diagnostic Criteria Met

This patient fulfills all diagnostic criteria for HHS:

• Glucose >600 mg/dL: Patient has glucose of 700 mg/dL 1
• Serum osmolality >320 mOsm/kg: Patient has osmolality of 322 mOsm/kg 1
• Altered mental status: Patient is sleepy, indicating altered consciousness 1
• Severe dehydration: Hypotension, tachycardia, and elevated BUN (59) with creatinine (2.1) indicate severe volume depletion 1
• Minimal ketones: Only small ketones in urine, not meeting DKA criteria 1
• Bicarbonate >15 mEq/L: Patient has bicarbonate of 19 mEq/L 1
• pH >7.3: The bicarbonate level suggests pH is above DKA threshold 1

Why Not Diabetic Ketoacidosis (DKA)

DKA requires glucose >250 mg/dL, venous pH <7.3, bicarbonate <15 mEq/L, and moderate to large ketonuria 2, 1. This patient's bicarbonate of 19 mEq/L and only small ketones exclude DKA as the primary diagnosis 2. While DKA can occur in type 2 diabetes, it typically requires severe insulin deficiency or specific precipitants 2.

Empagliflozin's Role as Precipitant

Empagliflozin significantly contributed to this crisis through multiple mechanisms:

• Osmotic diuresis: SGLT2 inhibitors cause persistent glucosuria, creating massive water and sodium losses that exceed the patient's ability to compensate 3, 4
• Volume depletion: The FDA label warns that empagliflozin causes intravascular volume contraction, with particular risk in elderly patients, those with renal impairment, and those on diuretics 4
• Acute kidney injury: The patient's elevated creatinine (2.1) and BUN (59) indicate prerenal azotemia from severe dehydration, a known complication of SGLT2 inhibitors 4, 5
• Reduced glucose-lowering efficacy: With declining renal function (creatinine 2.1), empagliflozin's glucose-lowering effect diminishes while osmotic diuresis continues 6, 7

A case report documented nearly identical presentation: a patient on empagliflozin developed severe hypernatremic dehydration (sodium 164 mmol/L), creatinine 2.1 mg/dL, and unconsciousness due to inability to replace water losses autonomously 5.

Critical Clinical Features

• Cardiovascular compromise: Tachycardia, hypotension, and audible S4 indicate severe volume depletion and cardiac strain 1, 8
• Leukocytosis: WBC of 14,000 suggests either stress response or possible infection as precipitant 1
• Hyponatremia: Sodium of 132 is falsely low due to hyperglycemia; corrected sodium is likely higher, contributing to hyperosmolality 8
• Prerenal azotemia: BUN:creatinine ratio >20:1 confirms volume depletion as primary cause of renal dysfunction 1

Immediate Management Priorities

Fluid resuscitation is the cornerstone of treatment:

• Begin isotonic saline (0.9% NaCl) at 15-20 mL/kg/h during the first hour to restore intravascular volume and renal perfusion 1, 8
• Monitor vital signs, urine output, and mental status closely; elderly patients require careful assessment to avoid fluid overload 1
• Once hemodynamically stable, switch to 0.45% NaCl to address free water deficit 8

Insulin therapy:

• Administer IV bolus of regular insulin 0.15 units/kg, followed by continuous infusion at 0.1 unit/kg/h 1
• Target glucose decline of 50-75 mg/dL per hour 1
• Add 5% dextrose to IV fluids when glucose approaches 250-300 mg/dL 8

Discontinue empagliflozin immediately:

• The FDA label mandates discontinuation in settings of reduced oral intake or fluid losses 4
• SGLT2 inhibitors should be stopped in any acute illness causing dehydration 9, 4

Electrolyte monitoring:

• Draw blood every 2-4 hours for glucose, electrolytes, BUN, creatinine, and osmolality 1
• Potassium replacement is critical as insulin therapy drives potassium intracellularly 1
• Ensure osmolality decrease does not exceed 3 mOsm/kg/h to prevent cerebral edema 1

Critical Pitfall to Avoid

Do not correct hyperglycemia or osmolality too rapidly. Overly aggressive correction can cause cerebral edema, particularly in HHS where osmotic shifts have been prolonged 1. The target is gradual normalization over 24-48 hours, not immediate correction 8.