The US Food and Drug Administration recently approved 2 combination products containing a basal insulin and a glucagon-like peptide 1 receptor agonist: insulin glargine/lixisenatide and insulin degludec/liraglutide. These agents were shown to be noninferior in lowering hemoglobin A1c compared to basal insulin and are indicated for patients inadequately controlled on basal insulin or glucagon-like peptide 1 receptor agonists alone. The clinical implications of these agents are unclear due to limitations in the clinical trials and limited recommendations in current guidelines. While these agents may provide financial and adherence benefits, their role is likely limited to the outpatient setting. With the availability of these agents, concerns with transitions of care arise due to multiple vulnerabilities in reconciling these agents throughout the inpatient admission and discharge process. Provider awareness of the availability and dosing of insulin glargine/lixisenatide and insulin degludec/liraglutide is essential to reduce errors in the medication reconciliation process.
Cardiovascular disease (CVD) is the most prevalent cause of morbidity and mortality in diabetic patients. Improvement in cardiovascular complications with glycaemic control and managing cardiovascular risk factors is well established. However, the impact of hypoglycaemic medications on CVD is of increasing importance. In 2008, the U.S. Food and Drug Administration issued study regulations for hypoglycaemic agents after rosiglitazone was shown to increase the incidence of myocardial infarction, and the European Medicines Agency provided their own guidance in 2012. As a result, multiple studies have been published evaluating the cardiovascular safety of newer hypoglycaemic medications. Empagliflozin and liraglutide are among the newer agents that have shown cardiovascular benefit and are now recommended for patients with CVD or are at an increased risk of CVD per the 2017 American Diabetes Association Guidelines. Given the influx of new literature and other ongoing studies, it is important to understand the cardiovascular safety of newer hypoglycaemic medications. The purpose of this article is to provide a comprehensive review of clinical trials conducted evaluating cardiovascular outcomes of newer hypoglycaemic medications and their role within diabetic management. Key Messages With the prevalence of cardiovascular disease in diabetic patients, clinicians should develop a medication regimen that provides both sufficient efficacy for diabetes while also maintaining cardiovascular safety. Of the new diabetic classes, empagliflozin, a sodium-glucose co-transporter 2 inhibitor, and liraglutide, a glucagon-like peptide-1 receptor agonist, have shown cardiovascular benefit in diabetic patients with established cardiovascular disease and are now recommended in current guidelines for this population. Ongoing trials will give more insight to whether cardiovascular benefit is a class effect with sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists and the cardiovascular safety of dipeptidyl peptidase-4 inhibitors.
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