Pharmacotherapy for diabetes management has expanded in recent years with several new drug classes. Current guidelines recommend several options for patients who have not reached their goal A1c on metformin monotherapy including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or basal insulin. However, if basal insulin is chosen as the first add-on treatment with metformin, the post-prandial blood glucose (PPG) often will remain elevated. A combination product that includes both a basal insulin plus a GLP-1 RA has the potential to addresses both fasting blood glucose and PPG … and perhaps has some other advantages over using either product alone.
According to the current (2016) ADA guidelines, no agent is “the preferred” second line therapy after metformin monotherapy — instead the benefits, risks, cost, and convenience of each option should be considered and treatment should be individualized. The liraglutide and cardiovascular outcomes in type 2 diabetes (LEADER) trial, which assessed the long-term cardiovascular effects of liraglutide, a GLP-1 receptor agonist, comes at an interesting time shortly after the publication of the empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes (EMPA-REG OUTCOME) trial. Both studies found a cardiovascular benefit. How, then, will the results of these trials affect the algorithm for type 2 diabetes management and more importantly, clinical practice?
After cardiovascular (CV) safety concerns emerged with rosiglitazone use, the Food and Drug Administration (FDA) now requires outcome studies to be performed for all new diabetes medications. The first CV safety study (ELIXA) for a drug in the glucagon-like peptide 1-receptor agonist (GLP-1 RA) class – lixisenatide - was published in December 2015. Lixisenatide is a once-daily injectable GLP-1 RA approved for use in Europe and awaits FDA approval in the United States.