What is the best approach to adding Januvia (sitagliptin) and Jardiance (empagliflozin) to a patient's regimen while considering discontinuation of Lantus (insulin glargine) with impaired renal function?

Transitioning from Insulin to Oral Agents in CKD Stage 3

Do not add Januvia (sitagliptin) or Jardiance (empagliflozin) at this time—instead, prioritize Jardiance first, reduce Lantus by 20%, and discontinue Januvia entirely given the patient's GFR of 51 mL/min/1.73 m².

Immediate Medication Adjustments

Prioritize Jardiance (Empagliflozin) as First-Line Therapy

Start Jardiance 10 mg once daily in the morning, as SGLT2 inhibitors provide cardiovascular and kidney benefits in patients with CKD and eGFR ≥30 mL/min/1.73 m², with benefits extending even when eGFR is 30-44 mL/min/1.73 m². 1

• The KDIGO 2020 guidelines strongly recommend treating patients with type 2 diabetes, CKD, and eGFR ≥30 mL/min/1.73 m² with an SGLT2 inhibitor (1A recommendation), with cardiovascular and kidney benefits seen across all CKD categories including eGFR 30-44 mL/min/1.73 m² 1
• These benefits occur despite reduced glucose-lowering efficacy at lower eGFR, and the cardiovascular/kidney benefits are out of proportion to HbA1c reductions, suggesting mechanisms beyond glucose lowering 1
• Jardiance can be initiated at eGFR 51 mL/min/1.73 m² without dose adjustment, though do not initiate if eGFR falls below 45 mL/min/1.73 m² 2

Reduce Lantus Dose by 20% When Starting Jardiance

Decrease Lantus from 6 units to 5 units (approximately 20% reduction) to prevent hypoglycemia when adding SGLT2 inhibitor therapy. 1

• For patients meeting glycemic targets who are receiving insulin, reducing or withdrawing the insulin dose may be necessary when adding SGLT2 inhibitors to prevent hypoglycemia 1
• The ACC 2020 consensus recommends reducing total daily insulin dose by approximately 20% when starting SGLT2 inhibitors if HbA1c is well-controlled at baseline or if there is a history of frequent hypoglycemic events 1
• With a current blood glucose of 120 mg/dL, this patient is at target, making insulin dose reduction essential 1

Do NOT Add Januvia (Sitagliptin) at This Time

Januvia should not be added because DPP-4 inhibitors are inferior to SGLT2 inhibitors for patients with CKD, and adding both simultaneously provides no additional cardiovascular or renal benefit. 1, 3

• KDIGO guidelines explicitly state that for patients with CKD not achieving glycemic targets despite metformin and SGLT2 inhibitor use, a long-acting GLP-1 receptor agonist is recommended—not a DPP-4 inhibitor 1
• DPP-4 inhibitors have shown cardiovascular safety but no cardiovascular benefit, unlike SGLT2 inhibitors which reduce cardiovascular death and heart failure hospitalization 3
• Sitagliptin requires dose adjustment at eGFR <45 mL/min/1.73 m² (50 mg daily for eGFR 30-44), making it less practical than continuing SGLT2 inhibitor therapy 3

Critical Monitoring Requirements When Starting Jardiance

Volume Status and Blood Pressure Monitoring

Assess for volume depletion risk before starting Jardiance, particularly given potential diuretic use, and monitor for symptoms of hypovolemia in the first few weeks. 1

• Consider decreasing thiazide or loop diuretic dosages before starting SGLT2 inhibitor treatment if the patient is on diuretics 1
• Educate the patient about symptoms of volume depletion (lightheadedness, orthostasis, weakness) and low blood pressure 1
• SGLT2 inhibitors may cause modest volume contraction, blood pressure reduction, and weight loss 1

Renal Function Monitoring

Expect a modest, reversible decrease in eGFR within the first few weeks of Jardiance initiation—this is hemodynamic in nature and not a reason to discontinue therapy. 1

• A reversible decrease in eGFR with commencement of SGLT2 inhibitor treatment may occur and is generally not an indication to discontinue therapy 1
• Long-term eGFR preservation has been reported with continuation of SGLT2 inhibitors despite initial eGFR decline 1
• Once initiated, it is reasonable to continue Jardiance even if eGFR falls below 30 mL/min/1.73 m², unless not tolerated or kidney replacement therapy is initiated 1

Genital Mycotic Infection Prevention

Educate the patient regarding potential for genital mycotic infections and importance of genital hygiene, as this is the most common adverse event with SGLT2 inhibitors. 1, 2

• Genital mycotic infections occur in approximately 5% or greater of patients treated with empagliflozin 2
• Monitor and treat genital mycotic infections as appropriate if they occur 2

Ketoacidosis Risk Mitigation

Withhold Jardiance during times of prolonged fasting, surgery, or critical medical illness when patients may be at greater risk for ketosis. 1

• Assess patients who present with signs and symptoms of metabolic acidosis (nausea, vomiting, abdominal pain, weakness) for ketoacidosis, regardless of blood glucose level 2
• Diabetic ketoacidosis can occur even if blood glucose readings are in the 150-250 mg/dL range 1
• If ketoacidosis is suspected, discontinue Jardiance, evaluate and treat promptly 2

Insulin Carbohydrate Ratio and Correction Scale Adjustments

Maintain Current Insulin-to-Carbohydrate Ratio Initially

Continue the 1 unit per 10 grams carbohydrate ratio for meal coverage, but monitor closely for hypoglycemia in the first 4 weeks after starting Jardiance. 1

• Instruct the patient to more closely monitor glucose at home for the first 4 weeks of SGLT2 inhibitor therapy, especially when on insulin 1
• The carbohydrate-to-insulin ratio should be reassessed if glucose after meals is consistently out of target 4

Adjust Correction Scale if Hypoglycemia Occurs

If hypoglycemia occurs, reduce the correction scale from 1 unit per 35 mg/dL to 1 unit per 45-50 mg/dL (increasing the insulin sensitivity factor by 10-20%). 4

• When hypoglycemia occurs, the insulin sensitivity factor should be adjusted rather than the basal dose 4
• Correction insulin should be adjusted based on insulin sensitivity factor, calculated as 1500/TDD or 1700/TDD 4

When to Consider Adding Januvia (If Ever)

Januvia Should Only Be Considered After Optimizing Jardiance

If glycemic targets are not met after 3-6 months of Jardiance therapy despite optimal dosing (25 mg daily), consider adding a GLP-1 receptor agonist rather than Januvia. 1

• For patients with CKD not achieving individualized glycemic targets despite use of metformin and SGLT2 inhibitor, a long-acting GLP-1 receptor agonist is recommended 1
• DPP-4 inhibitors like Januvia are considered only when SGLT2 inhibitors and GLP-1 receptor agonists cannot be used 1

If Januvia Must Be Used Due to Cost or Access Issues

If Januvia is eventually added, use 50 mg once daily (not 100 mg) given the patient's eGFR of 51 mL/min/1.73 m², which falls in the 45-59 range requiring dose reduction. 3

• Sitagliptin requires dose adjustment when eGFR is <45 mL/min/1.73 m², with 50 mg daily for eGFR 30-44 mL/min/1.73 m² 3
• At eGFR 51 mL/min/1.73 m², the patient is close to the threshold and may benefit from the reduced 50 mg dose to minimize accumulation risk 3
• Regular monitoring of renal function is needed to adjust dosing as eGFR changes 3

Common Pitfalls to Avoid

Do Not Continue Full-Dose Lantus When Adding Jardiance

Failing to reduce Lantus dose by 20% when adding Jardiance will result in hypoglycemia, as SGLT2 inhibitors provide additional glucose-lowering despite their primary cardiovascular/renal benefits. 1

Do Not Add Both Jardiance and Januvia Simultaneously

Adding both agents at once makes it impossible to assess individual drug effects and increases polypharmacy without additional cardiovascular or renal benefit. 1, 3

Do Not Discontinue Jardiance for Modest eGFR Decline

A reversible 5-10 mL/min/1.73 m² decrease in eGFR within the first few weeks is expected and hemodynamic in nature—do not stop Jardiance unless eGFR falls persistently below 45 mL/min/1.73 m² or the patient develops intolerance. 1, 2

Do Not Delay SGLT2 Inhibitor Initiation Due to "Borderline" eGFR

At eGFR 51 mL/min/1.73 m², the patient is well above the threshold for Jardiance initiation (eGFR ≥30 mL/min/1.73 m²), and delaying therapy deprives the patient of proven cardiovascular and kidney benefits. 1