What are suitable alternatives to Farxiga (dapagliflozin) for a patient with impaired renal function and a history of cardiovascular disease?

Alternative to Farxiga (Dapagliflozin) for Patients with Impaired Renal Function and Cardiovascular Disease

For patients with impaired renal function (eGFR <45 mL/min/1.73m²) and cardiovascular disease who cannot use dapagliflozin for glycemic control, empagliflozin is the preferred SGLT2 inhibitor alternative, as it has demonstrated cardiovascular benefits down to eGFR 30 mL/min/1.73m² and has no increased amputation risk compared to canagliflozin. 1

Primary Alternative: Empagliflozin

Empagliflozin should be the first-line SGLT2 inhibitor alternative for this patient population based on the following:

• Renal dosing advantage: While dapagliflozin is not recommended for glycemic control if eGFR <45 mL/min/1.73m², SGLT2 inhibitors as a class have shown cardiovascular benefit down to eGFR 30 mL/min/1.73m² 1

• Proven cardiovascular benefits: The EMPA-REG OUTCOME trial demonstrated significant reduction in cardiovascular death, myocardial infarction, and stroke in patients with type 2 diabetes and established atherosclerotic cardiovascular disease 1

• Superior safety profile: Empagliflozin has not shown increased amputation risk in post-hoc analyses, unlike canagliflozin which carries an FDA black box warning for lower limb amputation (6.3 vs. 3.4 per 1,000 patient-years) 1

• No increased bone fracture risk: Unlike canagliflozin, empagliflozin does not carry warnings for increased bone fractures 1

Second-Line Alternative: GLP-1 Receptor Agonists

If SGLT2 inhibitors are contraindicated or not tolerated, liraglutide is the preferred GLP-1RA based on:

• FDA-approved cardiovascular indication: Liraglutide is the only GLP-1RA with FDA approval specifically to reduce risk of MI, stroke, or cardiovascular death in adults with type 2 diabetes and cardiovascular disease 1

• Renal safety: No dose adjustment necessary with renal impairment, though data in end-stage renal disease are limited 1

• Dosing: Initiate at 0.6 mg subcutaneously daily, titrate slowly to 1.8 mg or maximally tolerated dose to minimize nausea 1

Alternative GLP-1RAs:

• Semaglutide: Showed numerically favorable cardiovascular results but was designed as a noninferiority trial; requires caution in patients with proliferative retinopathy 1
• Exenatide once weekly: Showed numerically favorable 3-point MACE results but did not reach statistical significance 1

Critical Monitoring Considerations

For SGLT2 Inhibitors (Empagliflozin):

Volume depletion monitoring is essential, particularly in this high-risk population:

• Monitor for orthostatic lightheadedness, especially in elderly patients or those on diuretics 1
• Check renal function within the first several weeks of therapy, as some patients may be "hyperresponders" with reversible eGFR decreases 1

Euglycemic ketoacidosis prevention:

• Discontinue 3-4 days before scheduled surgery 2
• Advise patients to stop medication and seek immediate care if experiencing dyspnea, nausea, vomiting, or abdominal pain 1
• Risk is very low in patients not requiring insulin therapy 1

Hypoglycemia prevention if patient is on insulin or sulfonylureas:

• Reduce insulin dose by 10-20% when initiating empagliflozin 3
• Reduce sulfonylurea dose by 50% or discontinue if already on minimal dose 1
• Self-monitor blood glucose closely for first 3-4 weeks 1

For GLP-1 Receptor Agonists (Liraglutide):

Gastrointestinal side effects:

• Start with lowest dose (0.6 mg daily) and up-titrate gradually every few weeks 1
• Advise eating smaller portions to minimize nausea 1
• Use with caution in patients with clinically significant gastroparesis 1

Hypoglycemia management:

• Same insulin/sulfonylurea dose reduction strategy as SGLT2 inhibitors 1
• Do not coadminister with DPP-4 inhibitors 1

Ophthalmologic monitoring:

• Ensure recent eye examination prior to semaglutide initiation if considering this alternative, particularly in patients with proliferative retinopathy 1

Agents to Avoid in This Population

Canagliflozin should be avoided in patients with:

• History of prior amputations 1
• Significant peripheral artery disease 1
• Active lower extremity soft tissue ulcers or infections 1
• History of osteoporosis (increased fracture risk) 1

Common Pitfalls

• Do not assume all SGLT2 inhibitors have identical safety profiles: Amputation and fracture risks vary significantly between agents 1
• Do not forget to adjust concomitant diabetes medications: Failure to reduce insulin or sulfonylurea doses leads to hypoglycemia 1, 3
• Do not continue SGLT2 inhibitors through surgical procedures: This increases ketoacidosis risk even with normal glucose levels 2
• Do not overlook volume status: Patients with impaired renal function are at higher risk for volume depletion with SGLT2 inhibitors 1