Newer antidiabetic agents, including sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, should be increasingly used in patients with type 2 diabetes and chronic kidney disease (CKD) because of the cardiorenal protection they provide, according to a scientific statement from the American Heart Association. "These newer agents are not mere antihyperglycemic drugs; rather, they are primary cardiorenal risk-reducing medications that need quick uptake across specialties to ensure appropriate delivery of care," Dr. Janani Rangaswami of Albert Einstein Medical Center and Thomas Jefferson University, in Philadelphia, told Reuters Health by email. "If correctly implemented, cardio-renal-metabolic care models can significantly help reduce the disease burden and health care costs related to cardiovascular disease (CVD) and CKD." Dr. Rangaswami and colleagues summarize the current literature on the cardiorenal protective effects with SGLT2 inhibitors and GLP-1-receptor agonists in patients with CKD and type-2 diabetes, review potential mechanistic pathways, summarize the literature on adverse effects, and provide practical guidance on a proposed collaborative care model in a new report in Circulation. Among the four SGLT2 inhibitors approved by the US Food and Drug Administration (FDA) for glycemic control, empagliflozin has been shown to reduce cardiovascular death; dapagliflozin has been shown to prevent hospitalization for heart failure; and canagliflozin has been shown to reduce cardiovascular death, major adverse cardiovascular events, and heart-failure hospitalizations. All three of these agents have been shown to slow the progression of albuminuria and reduce the risk of estimated GFR decline, dialysis, transplantation, or death resulting from kidney disease and end-stage kidney disease (ESKD). Initiation of these agents is not currently recommended in patients with advanced CKD (estimated GFR <30 mL/min/1.73 m2), but canagliflozin can be maintained in this range when initiated in higher estimated GFR ranges until the point of dialysis initiation or kidney transplantation. Clinicians should be aware of an increased risk of genital mycotic infections and the rare occurrence of euglycemic diabetic ketoacidosis with SGLT2 inhibitors, according to the authors. There are currently seven FDA-approved and marketed GLP-1-receptor agonists for the treatment of type-2 diabetes. Liraglutide and injectable semaglutide have both been shown to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke). Several GLP-1-receptor agonists have been shown to improve renal outcomes in patients with type-2 diabetes. Unlike the SGLT2 inhibitors, GLP-1 receptor agonists can be used safely in patients with moderate to severe CKD or ESKD. The proposed multidisciplinary care model aims to identify patients with type-2 diabetes at high risk for kidney events; select appropriate SGLT2 inhibitors, GLP-1-receptor agonists, or combinations thereof; adjust concomitant therapies; counsel patients; and follow patients closely for adverse events and to ensure treatment adherence. "Other key elements of a multidisciplinary model should include dieticians and specialty pharmacists who can play a very important role in ensuring high adherence to therapeutic lifestyle modification, which should be the first step in all patients with high CVD and CKD risk," Dr. Rangaswami said. "Having a dedicated pharmacist will greatly improve the ability to ensure that gaps in access to these medications are reduced. Finally, having dedicated care navigators to coordinate the complex care these patients need will also help bridge the current gaps in the delivery of these targeted therapies," he added. Co-author Dr. Peter A. McCullough of Baylor University Medical Center, in Houston, Texas, told Reuters Health by email, "SGLT2 inhibitors and GLP-1-receptor agonists are game-changing new drugs for type-2 diabetes that have sweeping implications for public-health strategies for this common and growing chronic disease. The opportunity to markedly reduce the numbers of patients on dialysis, being admitted to the hospital for heart and renal failure, and save lives makes widespread utilization an imperative for many stakeholders." "Out-of-pocket costs for these medications are the main barrier to widespread implementation," he said. "Drug companies, distributors, pharmacies, and benefits plan managers all work to unnecessarily increase the cost of these drugs to the consumer and thus reduce their utilization by the patients who need them the most." Dr. Yoshifumi Saisho of Keio University School of Medicine, Tokyo, Japan, who recently reviewed the cardiorenal protection provided by these agents, told Reuters Health by email, "The cardiorenal benefits are expected for individuals with type 2 diabetes and those at high risk for atherosclerotic cardiovascular disease (ASCVD), CKD, or heart failure, but also can be expected for those without diabetes." "Physicians should be aware of the ongoing evidence of cardiorenal benefits with these newer agents, as well as adverse effects, and should make an effort to identify patients with type-2 diabetes at high risk for kidney events by screening with eGFR and albuminuria as the first step to implement this collaborative care model," he said. "Building up and maintaining close communications among the specialists and primary-care providers is the main challenge to implementing a collaborative care model," added Dr. Saisho, who was not involved with the new statement. "A patient-centered approach and care are also key elements to avoid inappropriate use and adverse events of these drugs and to minimize polypharmacy." —Will Boggs, MD Source
