2015 ADA: CV safety, diabetes self-management and support

Focus on Diabetes

Key data presented at the 75th Scientific Sessions of the American Diabetes Association (ADA) included results from the TECOS and ELIXA trials, and a statement was released that outlines educational areas for diabetes self-management and support. The meeting, held at the Boston Convention and Exhibition Center on June 5–9, 2015, brought together more than 18,000 attendees, including nearly 15,000 clinicians from all 50 states and 130 countries. Highlights from these trials and the statement are covered in this article, and additional information from the 2015 ADA meeting can be accessed at .


No increased CV risks 
with sitagliptin 


The addition of sitagliptin (Januvia—Merck) to usual standard of care in patients with type 2 diabetes and cardiovascular (CV) disease did not increase the risk of major CV adverse events, hospitalization for heart failure, or other adverse events, according to results of the TECOS (Trial Evaluating Cardiovascular Outcomes with Sita-gliptin) trial presented at ADA and published in the New England Journal of Medicine.1


Data on dipeptidyl peptidase 4 (DPP-4) inhibitors such as saxagliptin (Ongylza—AstraZeneca) and alogliptin (Nesina—Takeda) have shown that there may be an increased risk of CV events in patients given these agents. Results of the SAVOR TIMI-53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus [SAVOR]–Thrombo-lysis in Myocardial Infarction [TIMI] 53) trial showed an increase in heart failure hospitalizations with use of saxagliptin in patients with type 2 diabetes who had a history of—or were at risk for—CV events. 


In addition, results from the EXAMINE (Examination of Cardio-vascular Outcomes: Alogliptin vs. Standard of Care in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome) trial showed a trend toward an increased risk of heart failure hospitalizations in patients given the drug compared with those receiving placebo, although the results were not statistically significant. 


To assess the long-term safety of sitagliptin, specifically in patients with established CV disease, the TECOS trial was conducted. This large, multicenter trial randomized 14,671 patients with type 2 diabetes and established CV disease (i.e., history of major coronary artery disease, ischemic cerebrovascular disease, or atherosclerotic peripheral arterial disease) to sitagliptin at a dose of 100 mg daily (or dose adjusted on the basis of renal function) or placebo in addition to their current diabetes regimen. 


After a median follow-up duration of 3 years, the investigators reported that there was no difference for the primary outcome, which was a composite of CV death, nonfatal myocardial infarction (MI), nonfatal stroke, or hospitalization for unstable angina, among the two groups (sitagliptin 11.4% vs. placebo 11.6%). 


In addition, no differences in the rate of hospitalizations for heart failure were observed between the sitagliptin and placebo groups (3.1% in each group). Other adverse events also occurred at similar rates in both groups, such as the overall incidence of infections, cancer, site-reported renal failure, or severe hypoglycemia. Confirmed acute pancreatitis events were more numerically common in the sitagliptin group than in the placebo group.


In April 2015, FDA’s Endocrinologic and Metabolic Drugs Advisory Com-mittee met to discuss the CV safety of saxagliptin and alogliptin. The committee voted 13 to 1 (1 abstained; 15 total votes) that the results of SAVOR demonstrated that use of saxagliptin in patients with type 2 diabetes has an acceptable CV risk profile, but 14 out of the 15 committee members recommended that FDA supplement the products’ labeling to add new safety information. 


For alogliptin, all 16 voting members concluded that the results of EXAMINE demonstrate that use of alogliptin in patients with type 2 diabetes has an acceptable CV risk profile, but 13 out of 16 committee members voted that safety information from the EXAMINE study should be added to the alogliptin labeling. To date, neither label has been updated to include this information. The results of the TECOS trial provide further reassurance that DPP-4 inhibitors have an acceptable CV risk profile, even with long-term use. 


First CV outcome data 
for GLP-1 agonist released 


The first CV outcomes study for a glucagonlike peptide–1 (GLP-1) agonist, lixisenatide (Lyxumia—Sanofi), found no evidence of increased cardiac risk compared with placebo, according to results of the ELIXA (Evaluation of Cardiovascular Outcomes in Patients with Type 2 Diabetes After Acute Coronary Syndrome During Treatment with Lixisenatide) trial presented at ADA.


ELIXA was a double-blind, parallel group trial designed to evaluate CV risk with use of lixisenatide compared with placebo in 6,068 patients with type 2 diabetes and high CV risk (i.e., patients who have recently experienced a spontaneous acute coronary syndrome event). Results showed no difference between groups in the composite primary endpoint, which was CV death, nonfatal MI, nonfatal stroke, or hospitalization for unstable angina. 


In addition, no signal for an increased risk of heart failure was observed with use of lixisenatide (hazard ratio 0.96 [95% CI 0.75–1.23]). Other adverse events also occurred at similar rates in both groups, such as pancreatitis (0.2% lixisenatide vs. 0.3% placebo), pancreatic cancer (<0.1% lixisenatide vs. 0.3% placebo), malignancy (2.9% lixisenatide vs. 2.6% placebo), and drug-related allergic reactions (0.2% in both groups). 


“There has been a cloud of suspicion over all new diabetes drugs, including GLP-1 agonists, over whether they may increase the risk for CV problems,” Marc Pfeffer, MD, PhD, Dzau Professor of Medicine at Harvard Medical, Senior Physician in Cardiology at Brigham and Women’s Hospital and Principal Investigator for the ELIXA trial, said in an ADA news release. 


“There has also been some hope that some of these drugs may improve CV health. GLP-1 receptor agonists were being used around the world while CV disease safety had yet to be established,” he continued. “This is the first report of a clinical trial designed to assess CV outcomes in this class of drugs, and we have shown that patients and their health care providers should have no cause for concern, even if they are at high risk for heart-related problems.” 


The ELIXA results pave the way for Sanofi to resubmit lixisenatide for approval in the United States, which the company expects to happen this year. In 2013, FDA’s request for an interim analysis of the ELIXA study prompted the manufacturer to pull the submission until it could present FDA with the complete findings from ELIXA. 


Diabetes self-management 
and support


A joint position statement of ADA, the American Association of Diabetes Educators, and the Academy of Nutrition and Dietetics on diabetes self-management and support in patients with type 2 diabetes was released at ADA’s meeting and published online simultaneously in Diabetes Care, The Diabetes Educator, and the Journal of the Academy of Nutrition and Dietetics.

The statement focused on two key concepts: diabetes self-management education (DSME), the process of facilitating the knowledge, skill, and ability necessary for diabetes self-care; and diabetes self-management support (DSMS), the support required for implementing and sustaining coping skills and behaviors needed to self-manage on an ongoing basis.


The statement noted that DSME and DSMS were traditionally provided through formal programs, but now convenient alternative settings, such as pharmacies, offer increased access to patients to obtain these services. The statement also recommended the four critical times DSME and DSMS should be provided or adjusted: 1) with a new diagnosis of type 2 diabetes, 2) annually for health maintenance and prevention of complications, 3) when new complicating factors influence self-management (e.g., stroke, depression), and 4) when transitions in care occur. 


At each of these times, a variety of educational topics should be included, such as healthy eating, being active, monitoring, proper medication use, problem solving, risk reduction, and healthy coping techniques. See Table 1 above for a list of examples of educational topics (the list is not comprehensive).


The joint statement highlighted that few people are receiving DSME and DSMS despite their proven benefits. They noted that patients with type 2 diabetes reported not being actively engaged by their providers, and that education and psychological services were not readily available to them. 


The organizations concluded, “It is imperative that the health care community, responsible for delivering quality care, mobilize efforts to address the barriers and explores resources for DSME/S in order to meet the needs of adults living with and managing type 2 diabetes.” (See pages 50–53 for more information.)


Reference


  1. New Engl J Med. 2015;373:232–242