What is the appropriate management for a 28‑year‑old man with type 2 diabetes on metformin and empagliflozin (Jardiance) who has mild transaminitis, low HDL cholesterol, severe hypertriglyceridemia, normal LDL and total cholesterol, microalbuminuria, glucosuria and ketonuria, with A1c pending?

Immediate Management of Severe Hypertriglyceridemia and Discontinuation of Jardiance

Stop Jardiance immediately and do not restart until the patient has recovered from this acute metabolic decompensation, as the combination of severe hypertriglyceridemia (525 mg/dL), ketonuria (15 mg/dL), and glucosuria (1000 mg/dL) indicates euglycemic diabetic ketoacidosis risk that is markedly elevated during acute illness. 1

Critical Safety Issue: Euglycemic Diabetic Ketoacidosis Risk

• The presence of ketonuria (15 mg/dL) with glucosuria (1000 mg/dL) in a patient on empagliflozin (Jardiance) represents a medical emergency requiring immediate SGLT2 inhibitor discontinuation, as euglycemic DKA can occur even with normal blood glucose levels and may present with nonspecific symptoms. 1, 2

• Withhold Jardiance during any acute illness with reduced oral intake, fever, vomiting, or diarrhea, and stop at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis. 3, 4

• The patient's severe hypertriglyceridemia (525 mg/dL) likely represents poor glycemic control and creates additional metabolic stress that increases ketoacidosis susceptibility when combined with SGLT2 inhibition. 5

Immediate Lipid Management Priority

• Initiate high-intensity statin therapy immediately (e.g., atorvastatin 40–80 mg daily or rosuvastatin 20–40 mg daily), as this 28-year-old with type 2 diabetes, severely low HDL (27 mg/dL), and triglycerides >500 mg/dL has extremely high cardiovascular risk requiring aggressive lipid management regardless of baseline LDL levels. 5

• The severely elevated triglycerides (525 mg/dL) are frequently secondary to poor glycemic control and are expected to improve substantially once HbA1c is reduced to <7%, but immediate statin therapy cannot be delayed. 5

• Consider adding fenofibrate or omega-3 fatty acids if triglycerides remain >200 mg/dL after 3 months of optimized glycemic control and statin therapy. 5

Glycemic Control Intensification

Metformin Optimization

• Increase metformin to 2000 mg daily (1000 mg twice daily with meals) to achieve maximal glucose-lowering effect, as the current dose is likely subtherapeutic and doses above 2000 mg add minimal benefit while increasing gastrointestinal intolerance. 1, 5

• Metformin must be continued as foundational therapy even when other agents are added, as it provides cardiovascular mortality benefit, reduces insulin requirements, and carries minimal hypoglycemia risk. 1, 5

Basal Insulin Initiation

• Start basal insulin (NPH or long-acting analog) at 10 units once daily at bedtime or 0.1–0.2 units/kg body weight, as the pending HbA1c is likely ≥9% given the severe glucosuria (1000 mg/dL) and ketonuria. 1, 5

• Titrate basal insulin by 2–4 units every 3 days until fasting glucose reaches 80–130 mg/dL without hypoglycemia. 1, 5

• The combination of metformin plus basal insulin is required for patients with severe hyperglycemia, as metformin monotherapy lowers HbA1c by only 0.9–1.1% and cannot achieve target control at these glucose levels. 5

Renal Protection Considerations

• The microalbuminuria (UACR 14 mg/g) is within normal range (<30 mg/g), but the patient's young age (28 years) with type 2 diabetes warrants aggressive cardiorenal protection once metabolic stability is achieved. 3

• Do not restart Jardiance until:

  • Ketonuria has completely resolved
  • Triglycerides have decreased to <200 mg/dL
  • The patient is metabolically stable on optimized metformin and basal insulin
  • HbA1c results are available to guide further therapy 1, 3

Monitoring and Follow-Up

• Check serum or urine ketones immediately to confirm the presence of ketoacidosis, as the urine ketone level of 15 mg/dL requires urgent evaluation for metabolic acidosis. 1

• Measure HbA1c, complete metabolic panel, and lipid panel to assess baseline glycemic control and rule out acute kidney injury. 1, 5

• Reassess HbA1c at 3 months after initiating metformin optimization and basal insulin; if HbA1c remains >7%, add a GLP-1 receptor agonist rather than restarting Jardiance. 1, 5

Alternative to Jardiance After Stabilization

• Consider a GLP-1 receptor agonist (e.g., semaglutide, liraglutide, dulaglutide) as the preferred third agent after metformin and basal insulin, as these provide 0.6–0.8% additional HbA1c reduction, 2–5 kg weight loss, minimal hypoglycemia risk, and proven cardiovascular benefit without the ketoacidosis risk of SGLT2 inhibitors. 1, 5

• GLP-1 receptor agonists are particularly appropriate for this young patient with severe hypertriglyceridemia and low HDL, as they promote weight loss and improve lipid profiles. 1, 5

Critical Pitfalls to Avoid

• Do not restart Jardiance while ketonuria persists, as this markedly increases the risk of life-threatening euglycemic DKA. 1, 2

• Do not delay insulin initiation while waiting for oral agents to work, as the severity of glucosuria and ketonuria indicates profound hyperglycemia requiring immediate combination therapy. 1, 5

• Do not discontinue metformin when insulin is added; it remains foundational therapy throughout intensification unless contraindicated. 1, 5

• Do not ignore the mild transaminitis (ALT 61 U/L); recheck liver function tests after metabolic stabilization, as SGLT2 inhibitors may be hepatotoxic and severe hypertriglyceridemia can cause hepatic steatosis. 6