Inhibition of PCSK9 in Dyslipidemia Patients with Diabetes
8:00 a.m.–9:00 a.m., Sunday
Ballroom 20A-C
Chair: Robert H. Eckel, MD
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
New Learnings from the Results of the Liraglutide Effect and Action in Diabetes—Evaluation of Cardiovascular Outcome Results (LEADER) Trial
9:00 a.m.–10:00 a.m., Sunday
Ballroom 20A-C
Chair: Robert E. Ratner, MD
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’s 76th Scientific Sessions in New Orleans. The primary results showed a reduction in major cardiovascular events and provided additional information on other important outcomes.
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
Results of the JDRF Reducing with Metformin Vascular Adverse Lesions in Type 1 Diabetes (REMOVAL) International Multicenter Trial
2:15 p.m.–4:15 p.m., Sunday
Hall A
Chair: William V. Tamborlane, MD
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 (CV) 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
