Cardiorenal Effects of Newer Diabetes Therapies to Be Explored at ADA

Two newer classes of therapy for type 2 diabetes (T2D) are becoming well-known for the benefits they provide beyond lowering blood glucose. Sodium glucose co-transporter 2 (SGLT2) inhibitors and some glucagon-like peptide-1 (GLP-1) receptor agonists have been shown to reduce cardiovascular risk and have been included in primary prevention guidelines from the American College of Cardiology and the American Heart Association.

More recently, cardiorenal outcomes have gained attention, as SGLT2 inhibitors in particular have been shown to prevent renal decline and reduce the risk of patients with T2D progressing to kidney failure. New findings in this area will be presented this weekend, during the virtual meeting of the 80^th American Diabetes Association Scientific Sessions.

Sunday’s 90-minute session, “Cardiorenal Metabolic Axis in Diabetes,” will cover the mechanisms of the cardio-renal syndrome, in which dysfunction in one organ can lead to problems with the other. The session will also review results from recent trials that have shown how therapies intended for T2D have cardiorenal impact, including the DAPA-HF trial, which showed that dapagliflozin (Farxiga) could reduce heart failure risk in patients regardless of T2D status; and CREDENCE, which found that canagliflozin (Invokana) significantly reduced the risk of renal decline.

Two other presentations involving renal results for dapagliflozin are planned for Saturday and Monday. Avivit Cahn, MD, of Hadassah Hebrew University Hospital, will present “Cardiorenal Outcomes with Dapagliflozin by Baseline Glucose Lowering Agents,” in a Saturday morning poster session. Itamar Raz, MD, from the same institution, will offer the oral presentation, “Effect of Dapagliflozin on Risk for Fast Decline in EGFR: Analyses from the DECLARE-TIMI 58 Trial,” on Monday.

Both presentations will examine data from the DECLARE-TIMI 58 trial, the cardiovascular outcomes study that first showed likely heart failure benefits for the SGLT2 inhibitor, made by AstraZeneca.

Another study featured in Saturday’s late-breaking poster session comes from China: Xiangyu Wang, MD, of Nanfang Hospital, Southern Medical University, will present, “Exenatide and Renal Outcomes in Patients with Type 2 Diabetes and Diabetic Kidney Disease: a Multicenter, Randomized, Parallel Study.” Exenatide, a GLP-1 receptor agonist, is sold under various brand names, including Byetta and Bydureon.

The poster session will also feature Ele Ferrannini, MD, of the National Research Council, who is presenting, “The Redox Balance Predicts Both Cardiovascular (CV) and Renal Outcomes in CANVAS,” referring to the large cardiovascular outcomes trial for canagliflozin, the SGLT2 inhibitor sold as Invokana by Janssen that was the first of the class to reach the market. Cardiorenal outcomes for this therapy were found in the CREDENCE findings last year.

Redox, or oxidation reduction, has been a topic in the literature this year as Ferrannini and others seek to understand the cardiorenal benefits of SGLT2 inhibitors that cannot be explained reducing glucose. Previously, these researchers have suggested that the action of these drugs promotes ketogenesis, creating an “efficient fuel” that aids organ systems that are otherwise under stress.

And, on Friday, an hourlong mini-symposium will examine whether gender makes a difference in renal and cardiovascular disease in diabetes. Chair Susanne Nicholas, MD, MPH, PhD, of the University of California at Los Angeles will lead a discussion featuring presentations by Christine Maric-Bilkan, PhD, of the National Institute of Diabetes and Digestive and Kidney Diseases, and Joel Neugarten, MD, of Montefiore Medical Center will discuss the question: is there a role of sex in the progression of renal and cardiovascular disease in diabetes?