American Association of Diabetes Educators 2017

American Association of Diabetes Educators 2017

Diabetes educators from across the globe gathered in Indianapolis (IN, USA) for the 2017 American Association of Diabetes Educators (AADE) conference. In a well-attended lecture on combination regimens for diabetes, Dr Kitte Wyne (Ohio State University, Columbus, OH, USA) advocated for the use of combination therapy according to American Association of Clinical Endocrinologists (AACE) treatment guidelines (see https://www.aace.com/sites/all/files/diabetes-algorithm-executive-summary.pdf, accessed 11 August 2017). Compared with the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) position statements,1, 2 the AACE algorithm recommends earlier intervention with combination therapy if patients are diagnosed with HbA1c ≥7.5%, as well as earlier initiation of basal insulin if patients are diagnosed with HbA1c >9%. Dr Wyne noted that providers wait an average of 18–20 months before switching or adding to treatment plans for their patients with diabetes, despite the recommendation to intensify or change therapy after 3 months of not meeting HbA1c goals. Fixed-dose and fixed-ratio combination products allow providers to give patients a single tablet or injection with superior efficacy and a milder side effect profile compared with monotherapy while also targeting multiple aspects of the ominous octet (eight organ dysfunctions in type 2 diabetes (T2D), including increased lipolysis, increased glucose reabsorption from the kidneys, decreased glucose uptake into the muscles, neurotransmitter dysfunction, heightened hepatic glucose production, increased glucagon secretion from the pancreatic α-cells, decreased insulin secretion from the pancreatic β-cells, and a decreased incretin effect). Basal insulin/glucagon-like peptide 1 (GLP-1) agonist fixed-ratio combinations, including Novo Nordisk’s (Copenhagen, Denmark) Xultophy (insulin degludec/liraglutide) and Sanofi’s (Paris, France) Soliqua (insulin glargine/lixisenatide) have proven to be highly effective antihyperglycemic agents, yet providers, particularly in the US, appear reluctant to prescribe them. Dr Wyne also addressed the amputation signal seen for Johnson & Johnson’s (New Brunswick, NJ, USA) sodium–glucose cotransporter 2 (SGLT-2) inhibitor Invokana (canagliflozin) in the Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes (CANVAS) study,3 calling for a dedicated clinical study of patients with diabetes and peripheral vascular disease, because many people with amputations in the CANVAS trial had baseline peripheral vascular disease.

Dr Anthony McCall (University of Virginia, Charlottesville, VA, USA) reviewed tools for cardiovascular risk management in diabetes, describing how cardiologists seem eager to prescribe the SGLT-2 inhibitor empagliflozin, branded by Lilly (Indianapolis, IN, USA) and Boehringer Ingelheim (Ingelheim, Germany) as Jardiance, and the GLP-1 agonist liraglutide, branded by Novo Nordisk as Victoza, to prevent cardiovascular events and cardiovascular death. Both these diabetes drugs demonstrated cardiovascular benefit in the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME)4 and Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trials,5 respectively, and Jardiance has even received an expanded indication for the reduction of cardiovascular death. A similar cardiovascular indication for Victoza is still under US Food and Drug Administration (FDA) review, although it has been granted by the European Medicines Agency (EMA) for the European label. At the FDA Advisory Committee meeting for Jardiance, a 12–11 vote in favor of the Jardiance label update was cast: half the members of this panel were cardiologists and the other were half endocrinologists, and all the cardiologists favored approval. Dr McCall suggested that endocrinologists on the Jardiance Advisory Committee may have been more skeptical about the statistical significance of the EMPA-REG OUTCOME results because the hazard ratios for on treatment analysis and protocol analysis crossed the line of unity, whereas the upper bound of the 95% confidence interval for intent to treat analysis was <1.00. Dr McCall also acknowledged that most real-world patients will not perfectly match the average participant profile in a diabetes cardiovascular outcomes trial, but he still advocated for the use of Jardiance and Victoza. He also noted that many people with diabetes and cardiovascular risk, especially women and minorities, do not get statins and good blood pressure control. Further, a diagnosis of diabetes confers the same risk for myocardial infarction as a person who has no diabetes but has had a prior myocardial infarction. Investigating these agents in primary prevention is a future direction for research. Notably, Dr McCall recommended prescribing empagliflozin instead of canagliflozin to T2D patients with peripheral vascular disease, because the CANVAS study found a nearly twofold risk for lower limb amputations associated with canagliflozin versus placebo, and peripheral vascular disease is a known precipitating factor for amputations.