How to manage a patient with hyperglycemia, elevated liver enzymes, hyperkalemia, and hypercalcemia on Januvia (sitagliptin), Jardiance (empagliflozin), fenofibrate, losartan, and carvedilol?

Management of Hyperglycemia, Elevated Liver Enzymes, Hyperkalemia, and Hypercalcemia in a Patient on Multiple Medications

Immediately discontinue Jardiance (empagliflozin) due to the patient's reduced eGFR (71 mL/min/1.73m²) approaching the threshold for discontinuation, and because SGLT2 inhibitors are contraindicated when eGFR falls persistently below 45 mL/min/1.73m² and can contribute to electrolyte abnormalities including hypercalcemia. 1

Immediate Medication Adjustments Required

Discontinue Jardiance (Empagliflozin)

• The FDA label explicitly states to discontinue JARDIANCE if eGFR falls persistently below 45 mL/min/1.73m² and not to initiate if eGFR is below 45 mL/min/1.73m². 1 With an eGFR of 71, this patient is approaching the threshold and has multiple electrolyte abnormalities that warrant immediate discontinuation.
• SGLT2 inhibitors cause osmotic diuresis that can lead to dehydration, reduced calcium excretion, and potentially contribute to hypercalcemia, particularly in patients with reduced renal function. 2
• The combination of hyperkalemia, hypercalcemia, and declining renal function creates a high-risk scenario for acute kidney injury with continued SGLT2 inhibitor use. 1

Address Hyperkalemia (K+ 5.7 mEq/L)

Reduce or discontinue carvedilol immediately, as beta-blockers are a documented cause of hyperkalemia, particularly in patients with chronic kidney disease. 3, 4

• Carvedilol specifically has been reported to cause hyperkalemia in patients with stage III chronic kidney disease, with potassium levels normalizing after dose reduction. 3
• The combination of carvedilol with losartan (an ARB) significantly increases hyperkalemia risk, as both medications impair potassium excretion through different mechanisms. 5
• Reduce carvedilol from 6.25 mg twice daily to 3.125 mg twice daily or discontinue entirely based on the case report showing potassium normalization with dose reduction. 3
• Consider alternative beta-blocker options if cardiac indication is compelling, though all beta-blockers carry hyperkalemia risk. 4

Reduce losartan dose by 50% or temporarily discontinue given the combined effect with carvedilol on potassium homeostasis. 5

Manage Elevated Liver Enzymes (AST 139, ALT 106)

Discontinue or reduce carvedilol dose, as it has documented hepatotoxicity with elevated transaminases that normalize upon discontinuation. 6

• Carvedilol-induced hepatotoxicity presents with elevated liver function tests that return to normal within three weeks of discontinuation. 6
• Evaluate fenofibrate contribution to transaminitis, as fibrates can cause hepatotoxicity, particularly when combined with statins (patient is on atorvastatin 40 mg). 7
• The combination of statin plus fenofibrate has not been shown to improve cardiovascular outcomes and is generally not recommended, though may be considered in specific lipid profiles. 7
• Monitor liver function tests weekly initially after medication adjustments. 8

Address Hypercalcemia (11.4 mg/dL)

Discontinue Jardiance immediately, as SGLT2 inhibitors can cause severe hypercalcemia through osmotic diuresis-induced dehydration and reduced calcium excretion. 2

• The first reported case of SGLT2 inhibitor-associated hypercalcemia showed calcium levels of 17.4 mg/dL with canagliflozin, resolving with saline hydration after drug discontinuation. 2
• Evaluate for excessive calcium intake (patient may be taking Tums or calcium supplements not listed in medication history). 2
• Initiate aggressive saline hydration (0.9% NaCl at 150-200 mL/hour if cardiac function permits) to promote calcium excretion. 2
• Monitor serum sodium closely during saline therapy, as osmotic diuresis can cause rapid hypernatremia. 2

Glycemic Management Optimization

Adjust Diabetes Medications

Continue Januvia (sitagliptin 100 mg daily) as DPP-4 inhibitors are safe in chronic kidney disease with appropriate dosing and do not cause hypoglycemia as monotherapy. 8

Reduce glipizide dose by 50% immediately to prevent hypoglycemia after discontinuing Jardiance and reducing other medications. 7

• Sulfonylureas should be discontinued when adding or removing other glucose-lowering agents if glycemic levels are close to target. 7
• Glipizide is the preferred sulfonylurea in hepatic impairment as it lacks active metabolites. 8
• Monitor blood glucose every 4-6 hours during medication transition period. 9

Consider GLP-1 Receptor Agonist Addition

Add a GLP-1 receptor agonist with proven cardiovascular benefit once acute issues resolve, as this patient has established cardiovascular disease (on carvedilol, losartan, aspirin, atorvastatin). 7

• The 2018 ADA/EASD consensus recommends GLP-1 RA for patients with clinical cardiovascular disease. 7
• GLP-1 receptor agonists undergo proteolytic degradation, not hepatic metabolism, requiring no dose adjustment for hepatic or renal impairment. 8
• GLP-1 RA should be considered before insulin initiation, allowing lower glycemic targets with lower hypoglycemia risk. 7

Monitoring Protocol

Immediate (First 48-72 Hours)

• Serum potassium every 12 hours until below 5.2 mEq/L. 10
• Serum calcium every 12 hours until below 10.3 mg/dL. 10
• Blood glucose monitoring every 4-6 hours while awake. 9
• Liver function tests at 48 hours to assess response to carvedilol/fenofibrate adjustment. 8
• Renal function (BUN/creatinine, eGFR) daily to monitor for acute kidney injury. 1

Short-term (First 2 Weeks)

• Serum potassium twice weekly until stable on new medication regimen. 3
• Liver function tests weekly until normalized or stable. 6
• Renal function weekly to ensure stability after SGLT2 inhibitor discontinuation. 1

Long-term

• HbA1c in 3 months to assess glycemic control after medication changes. 7
• Lipid panel in 3 months to evaluate need for fenofibrate continuation. 7
• Annual screening for diabetic kidney disease with urine albumin-creatinine ratio. 7

Critical Pitfalls to Avoid

Do not restart Jardiance even after electrolyte normalization given the patient's borderline eGFR and multiple risk factors for complications. 1

Do not continue both carvedilol and losartan at full doses in the setting of hyperkalemia and stage III chronic kidney disease, as this combination dramatically increases hyperkalemia risk. 3, 5

Do not attribute elevated transaminases solely to fatty liver disease without considering medication-induced hepatotoxicity from carvedilol and fenofibrate. 6

Avoid therapeutic inertia - the 2022 ADA/EASD consensus emphasizes re-evaluating medication-taking behaviors and side effects at every visit. 7

Do not use combination statin-fibrate therapy unless specific lipid indications exist (triglycerides >204 mg/dL and HDL <34 mg/dL in men), as this combination has not shown cardiovascular benefit and increases myositis risk. 7