AHA scientific statement reviews research on drugs for diabetes and chronic kidney disease

The advent of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists could reduce cardiovascular adverse events and progression to end-stage kidney disease, the American Heart Association (AHA) scientific statement noted.


A new scientific statement summarizes the current literature on the cardiorenal protective effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with chronic kidney disease and type 2 diabetes. The scientific statement by the American Heart Association was published Sept. 28 by Circulation.

Several potential mechanisms exist for beneficial effects in both drug classes, and they may be independent of their antihyperglycemic effects, according to the statement. For the SGLT-2 inhibitors, some of these mechanisms include the activation of tubuloglomerular feedback and resulting reductions in intraglomerular pressure, blood pressure, weight, and uric acid, as well as diuresis and higher red-cell mass. Diuretic effects of SGLT-2 inhibitors may play a role in that class's heart failure-specific benefits. Potential mechanisms for the GLP-1 receptor agonists include the activation of tubuloglomerular feedback, reduced efferent arteriole vasoconstriction at the glomerulus, and reduced sodium reabsorption and oxidative stress, which may reduce renal inflammation.

The scientific statement also summarizes the literature on adverse effects in patients who have chronic kidney disease and have or are at risk for cardiovascular disease. An increased risk of genital mycotic infections is the most common adverse event attributable to SGLT-2 inhibitors. Advice on daily hygienic measures such as rinsing the genital area after voiding and before bedtime significantly lessened the infection risk and improved adherence to SGLT-2 inhibitor treatment over a three-year period, the statement noted.

Urinary tract infections also have been reported with SGLT-2 inhibitors, but the rate was not higher compared with placebo in clinical trials. Case reports linking Fournier gangrene with the use of SGLT-2 inhibitors prompted an FDA warning in August 2018. A claims-based analysis showed a slight, but not statistically significant, increase in risk of Fournier gangrene of about one case per 10,000 men treated with SGLT-2 inhibitors compared with men treated with other antihyperglycemic agents. Nevertheless, given the morbidity associated with necrotizing fasciitis, a careful discussion of the possibility of serious genital soft-tissue infections is important, according to the statement.

The statement provides practical guidance on a proposed collaborative care model bridging cardiologists, nephrologists, endocrinologists, and primary care physicians. Although SGLT-2 inhibitors and GLP-1 receptor agonists are typically started by primary care physicians or endocrinologists, integrated multispecialty care has distinct advantages, according to the statement. Given limited access to the approximately 8,000 practicing endocrinologists in the United States, high-risk diabetes patients may more frequently encounter other medical subspecialists such as nephrologists and cardiologists, increasing opportunities to optimize therapeutic regimens. Multidisciplinary care pathways may lessen prescribing uncertainties and facilitate early and longitudinal follow-up. Innovative care approaches such as fully integrated multidisciplinary ambulatory centers are being considered nationally, according to the statement.