Results from seven major clinical trials will be reported at the Scientific Sessions. Here’s a brief overview of each:
Friday, June 9
4:15 p.m.–5:15 p.m.
A Heavy Heart—Metals, Diabetes, and Cardiovascular Disease Outcomes
Chair: David M. Nathan, MD
This session will explore the importance of cardiovascular events in patients with diabetes and suggest novel avenues to treat residual risk. Presentations will emphasize residual atherosclerotic risk despite efforts with evidence-based cardiac care, review the pathobiology of ubiquitous toxic metal pollutants such as lead and cadmium, and relate those findings to reports from NHANES, the Strong Heart Study, and other epidemiologic cohorts. Presenters will also consider whether these toxic metals may be reversible risk factors for atherosclerosis, particularly in patients with diabetes, based on the unexpected results of the Trial to Assess Chelation Therapy.
Presentations and speakers:
- Introduction, David M. Nathan, MD
- Type 2 Diabetes and Residual Risk following Acute Myocardial Infarction—Still There after All These Years, Mikhail N. Kosiborod, MD
- Metals, Diabetes, and Cardiovascular Risk―From Mechanisms to Epidemiology, Ana Navas-Acien, MD, PhD
- Benefits of Metal Chelation on Cardiovascular Risk in Patients with Diabetes―Is There a New Treatment Strategy on the Horizon?, Gervasio A. Lamas, MD
- Question and Discussion Period
Sunday, June 11
8:00 a.m.–9:00 a.m.
Inhibition of PCSK9 in Dyslipidemia Patients with Diabetes
Chair: Robert H. Eckel, MD
Despite the widespread use of statin therapy, many individuals with diabetes mellitus (DM) fail to attain desired lipid goals even with optimal standard of care, and are therefore exposed to a residual risk of cardiovascular (CV) events. Furthermore, CV risk increases with advanced duration of DM, particularly in insulin-treated patients. Lipid management may be further complicated in individuals with DM due to their unique lipid profiles (with frequent mixed dyslipidemia). Effective treatment of increased LDL-C in high-risk patient populations has been demonstrated with PCSK9 inhibitors on a background of maximally tolerated statin therapy, with Phase 3 data showing comparable lipid-lowering efficacy in patients with and without DM. Although correlations between PCSK9 levels and glucose and insulin levels have been reported in some prior studies, analyses of data from the PCSK9 inhibitor trials have found no impact of the drugs on glucose homeostasis versus controls. However, none of the completed trials to date were designed to specifically study DM populations, and they included limited numbers of insulin-treated individuals, particularly those with type 1 DM. Dedicated studies with PCSK9 inhibitors in individuals with DM will report on the safety, tolerability, glycemic-related endpoints, and efficacy in getting patients to goal.
Presentations and speakers:
- Lipid Management in Individuals with Diabetes at High Cardiovascular Risk—What Are the Unmet Needs?, Kausik K. Ray, MB, ChB, MD
- PCSK9 and Diabetes, Bertrand Cariou, MD, PhD
- ODYSSEY DM Program—Design and Study Populations, Dirk Müller-Wieland, MD
- Alirocumab and Insulin-Treated Diabetes—Insights from the ODYSSEY DM-INSULIN Study, Lawrence Leiter, MD, FRCPC, FACP, FACE, FAHA
- Alirocumab vs. Usual Care in Diabetes with Mixed Dyslipidemia—ODYSSEY DM-DYSLIPIDEMIA Study, Robert R. Henry, MD
- Independent Commentary, Henry N. Ginsberg, MD
9:00 a.m.–10:00 a.m.
New Learnings from the Results of the Liraglutide Effect and Action in Diabetes—Evaluation of Cardiovascular Outcome Results (LEADER) Trial
Chair: Robert E. Ratner, MD
Results from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial (NCT01179048) were reported last year at the ADA 76th Scientific Sessions in New Orleans. The primary results showed a reduction in major cardiovascular events and provided additional information on other important outcomes. Now, one year later, members of the steering committee and investigators will provide an update on the trial, including additional analyses of the cardiovascular outcomes, new analyses of clinical and metabolic efficacy, as well as updated analyses of safety outcomes.
Presentations and speakers:
- Cardiovascular Outcomes in LEADER—Recap and New Analyses, Steven E. Nissen, MD, MACC
- New Results—Long-Term Clinical and Metabolic Data, Richard E. Pratley, MD
- New Results—Safety, Stephen C. Bain, MD
2:15 p.m.–4:15 p.m.
Results of the JDRF Reducing with Metformin Vascular Adverse Lesions in Type 1 Diabetes (REMOVAL) International Multicenter Trial
Chair: William V. Tamborlane, MD
In this symposium, the main results of the REMOVAL trial of metformin in type 1 diabetes (NCT01483560) will be presented for the first time. Metformin is used first-line in type 2 diabetes, as it may reduce cardiovascular risk. Adults with type 1 are also at high cardiovascular risk and are sometimes treated with metformin adjunct therapy. However, although recent trials up to 12 months in duration have shown that metformin can reduce insulin dose requirement and stabilize weight in type 1, there are no data on cardiovascular effects or even medium-term safety.
REMOVAL is a three-year double-blind, randomized, placebo-controlled trial examining the effects of metformin on adults with type 1 diabetes aged 40 years or above. The primary endpoint is progression of averaged mean far wall common carotid intima-media thickness measured by ultrasonography; other endpoints include A1C, weight, LDL cholesterol, insulin requirement, retinopathy, endothelial function, and frequency of hypoglycemia. With 428 individuals randomized in 23 international centers (Australia, Canada, Denmark, the Netherlands, and the United Kingdom), REMOVAL is the largest and longest clinical trial of adjunct metformin therapy in type 1 diabetes to be conducted to date. It will provide clinically meaningful data on metformin’s potential to impact CV disease and other long-term complications.
REMOVAL was funded by a JDRF Strategic Research Award. Metformin and matching placebo were donated by Merck KGaA (Germany). Endothelial function data were acquired in collaboration with Itamar Medical (Israel).
Presentations and speakers:
- Introduction, Study Rationale, and Design, Helen M. Colhoun, MD
- Study Population, Alicia J. Jenkins, MD
- Glycemia, Irene M. Hramiak, MD, FRCP(C), FACP
- Primary Endpoint, Nishi Chaturvedi, MD, MRCP
- Clinical and Metabolic Outcomes, John R. Petrie, MB, ChB, PhD
- Retinal Outcomes, Barbara E.K. Klein, MD, MPH
- Safety, Martijn Brouwers, MD
- Conclusions, Peter Rossing MD, DMSc
- Perspective, Naveed Sattar, MD, PhD
- Question and Discussion Period
Monday, June 12
2:15 p.m.–3:15 p.m.
Cardiovascular Safety of Insulin Degludec vs. Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) Trial Results
Chair: Steven P. Marso, MD
DEVOTE is a long-term, multicenter, multinational, randomized, double-blinded, parallel group and event-driven trial conducted to confirm the cardiovascular safety of Tresiba® (insulin degludec) compared to insulin glargine U100. In the trial, 7,637 people with type 2 diabetes at high risk of cardiovascular disease were randomized to treatment with either Tresiba® or insulin glargine U100 in vial in addition to standard of care.
“The major secondary endpoint focused on severe hypoglycemia. Previously, the ORIGIN trial demonstrated the cardiovascular safety of insulin glargine versus usual care. Prior shorter-duration, open-label studies have suggested that degludec is associated with a lower risk of severe hypoglycemia,” said John B. Buse, MD, PhD, who will discuss the clinical implications of the study.
Presentations and speakers:
- Introduction and Trial Design, Steven P. Marso, MD
- Cardiovascular Outcomes, Darren K. McGuire, MD, MHSc
- Glycemic Efficacy and Hypoglycemia, Bernard Zinman, CM, MD, FRCPC, FACP
- Safety, Richard E. Pratley, MD
- Conclusion and Clinical Implications, John B. Buse, MD, PhD
- Independent Commentary, Elizabeth R. Seaquist, MD
3:15 p.m.–4:15 p.m.
The Integrated Results of the CANVAS Program
Chair: David R. Matthews, BM, BCh, DPhil
Canagliflozin is an SGLT2 inhibitor approved for the treatment of adults with type 2 diabetes. Across Phase 3 trials in a broad range of patients, canagliflozin has demonstrated glycemic improvements, as well as reductions in body weight and blood pressure. The CANagliflozin cardioVascular Assessment Study (CANVAS) and CANVAS–Renal (CANVAS-R) trials enrolled more than 10,000 patients with type 2 diabetes and a history or high risk of cardiovascular disease in order to assess the cardiovascular safety and efficacy of canagliflozin. The trials are similar in design and in the enrolled patient population. The findings of these studies will more clearly define the balance of risks and benefits of canagliflozin, as well as provide substantial additional insight into the cardiovascular outcomes of the SGLT2 inhibitor class more broadly. The results of the integrated analysis of CANVAS and CANVAS-R will be reported.
Presentations and speakers:
- Background to the Design of the Trials, Gregory R. Fulcher, MBBS, MD
- Methods for the Trials and the Integrated Analyses, Kenneth W. Mahaffey, BS, MD
- Effects on Cardiovascular Outcomes, Bruce Neal, MB, ChB, PhD
- Effects on Renal Outcomes, Dick de Zeeuw, MD, PhD
- Effects on Safety Outcomes, Vlado Perkovic, MBBS, PhD
- Implications for Clinical Practice, David R. Matthews, BM, BCh, DPhil
- Independent Commentary, Clifford J. Bailey, PhD, FRCP Edin, FRCPath
4:30 p.m.–6:30 p.m.
Type 1 Diabetes Immune Intervention Trials
Chair: Chantal Mathieu, MD, PhD
Where are we with disease modifying therapy in type 1 diabetes? This session will present results from multiple landmark clinical trials including the international Diabetes TrialNet’s Oral Insulin Prevention Trial. This double masked, placebo controlled study is the largest and longest Oral Insulin Prevention trial ever conducted. Results from TrialNet’s companion study, Immune effects of Oral Insulin, will also be presented as well as data from Sweden using GAD vaccine. The question for all of these studies is whether treatment at early stages of disease can delay progression to clinical (stage 3) type 1 diabetes. Finally, a fourth trial will report the results of intervention with imatinib (Gleevec) at stage 3 of disease (recent-onset, clinical type 1 diabetes).
Presentations and speakers:
Type 1 Diabetes TrialNet Oral Insulin Trial
- Introduction and Background, Jay S. Skyler, MD, MACP
- Results and Conclusions, Desmond Schatz, MD
- An Oral Insulin Mechanistic Study, Peter A. Gottlieb, MD
- Independent Commentary, David M. Maahs, MD, PhD
Imatinib (Gleevec) in New-Onset Type 1 Diabetes
- Background and Results, Stephen E. Gitelman, MD
DIAPREV-IT Trial with GAD-Vaccine
- Introduction and Background, Åke Lernmark, PhD
- Results and Conclusions, Helena Elding Larsson, MD, PhD
- Independent Commentary, Joseph Wolfsdorf, MB, BCh