Alternative Therapies for Patients with Impaired Renal Function and Cardiovascular Disease

Primary Alternative: Empagliflozin

The American College of Cardiology recommends empagliflozin as the first-line SGLT2 inhibitor alternative for patients with impaired renal function and cardiovascular disease, due to its demonstrated cardiovascular benefits down to eGFR 30 mL/min/1.73m² and lack of increased amputation risk compared to canagliflozin [@ understrength renal dosing advantage 1, 2
Empagliflozin has shown significant reduction in cardiovascular death, myocardial infarction, and stroke in patients with type 2 diabetes and established atherosclerotic cardiovascular disease, according to the EMPA-REG OUTCOME trial 1, 2
Empagliflozin has a superior safety profile, with no increased amputation risk and no warnings for increased bone fractures, unlike canagliflozin 3, 2
The American College of Cardiology suggests that empagliflozin has proven cardiovascular benefits, with a significant reduction in cardiovascular death, myocardial infarction, and stroke in patients with type 2 diabetes and established atherosclerotic cardiovascular disease 1, 2

Liraglutide is the preferred GLP-1RA for patients with impaired renal function and cardiovascular disease, due to its FDA-approved cardiovascular indication and lack of required dose adjustment with renal impairment 1, 2
The American College of Cardiology recommends initiating liraglutide at 0.6 mg subcutaneously daily, with gradual titration to 1.8 mg or maximally tolerated dose to minimize nausea 1, 2
Semaglutide showed numerically favorable cardiovascular results, but requires caution in patients with proliferative retinopathy 4, 1, 2

The American College of Cardiology suggests monitoring for orthostatic lightheadedness, especially in elderly patients or those on diuretics, and checking renal function within the first several weeks of empagliflozin therapy 4
Patients on empagliflozin should be advised to stop medication and seek immediate care if experiencing dyspnea, nausea, vomiting, or abdominal pain, to prevent euglycemic ketoacidosis 3, 5
The American College of Cardiology recommends reducing insulin dose by 10-20% when initiating empagliflozin, and reducing sulfonylurea dose by 50% or discontinuing if already on minimal dose, to prevent hypoglycemia 4, 6

Canagliflozin should be avoided in patients with a history of prior amputations, significant peripheral artery disease, active lower extremity soft tissue ulcers or infections, or history of osteoporosis, due to increased amputation and fracture risk 4, 2, 1