In November of 2018, the American College of Cardiology released the 2018 ACC Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients with Type 2 Diabetes and Atherosclerotic Cardiovascular Disease (and it was endorsed by the American Diabetes Association).  The report poses this question: Are clinicians who manage type 2 diabetes too consumed with glycemic control rather than focusing on the more important goal of overall cardiovascular risk reduction and preventing CV death? CV specialists, and all other healthcare professionals, should be aware of the strong clinical evidence supporting the use of newer glucose-lowering therapies. Select sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) reduce the risk of major adverse cardiovascular events, seemingly unrelated to their glucose-lowering effects. The consensus pathway is intended to guide clinicians and patients to consider initiating these therapies in individuals with type 2 diabetes and clinically established ASCVD … provided they do not have end-stage renal disease and are not pregnant or breastfeeding.

 

Of the SGLT2 inhibitors, empagliflozin and canagliflozin reduce HF hospitalization, nonfatal myocardial infarction, and nonfatal stroke; empagliflozin also reduces the risk of CV and all-cause mortality, making it the preferred drug in this class. The SGLT2 inhibitors also offer nephroprotection.  In clinical trials, the SGLT2 inhibitors slowed the progression of kidney disease, reducing the incidence or worsening of nephropathy. Although these therapies have several benefits, they may not be appropriate for every patient. Some factors to consider are the increased risk of genital mycotic infections and euglycemic diabetic ketoacidosis witnessed with SGLT2 inhibitors. There was also an increased risk for lower limb amputation or bone fracture associated with canagliflozin in the CANVAS study. Volume depletion and hypotension could also occur with these medications.

 

Currently, liraglutide is the only FDA-approved GLP-1RA to definitively reduce the risk of CV events. However, studies suggest that semaglutide, lixisenatide, and exenatide-ER each have some favorable CV effects, although the magnitude and combination of benefits are different for each agent. Cumulatively, these results suggest a possible class effect. GLP-1RAs may not be the best option in patients with a history of pancreatitis, severe renal impairment or ESRD, gastroparesis, diabetic retinopathy or a family history of medullary thyroid cancer.

 

Products vary in price, route of administration, adverse events, and ease of use which should be taken into consideration. Several studies are underway that will provide new evidence regarding mortality, quality of life, and achieving optimal outcomes in these high-risk patients using a team-based approach.