Results of the ODYSSEY study presented at the American Diabetes Association’s 77th Scientific Sessions.
The results from 2 OSYSSEY DIABETES studies were presented at the “Inhibition of PCSK9 in Dyslipidemia Patients with Diabetes” symposium during the American Diabetes Association’s 77th Scientific Sessions.
The investigators found that the PCSK9 inhibitor alirocumab reduced both LDL cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) in patients with type 2 diabetes.
Patients with diabetes have an increased risk of high cholesterol, which results in an elevated risk of cardiovascular disease (CVD). Receptors on the liver bind to cholesterol and break it down. PCSK-9 is a protein that reduces the activity of the receptors, which increases cholesterol levels.
Alirocumab is an FDA-approved monoclonal antibody that stops PCSK9 from reducing the efficacy of the liver’s receptors. This allows for more cholesterol to be broken down and reduces its levels.
The ODYSSEY DM-Insulin Trial is a phase 3 study that included patients with type 1 and type 2 diabetes who had high cardiovascular risks and inadequately controlled hypercholesterolemia. The investigators only presented findings for patients with type 2 diabetes.
Included in the analysis were 441 patients with type 2 diabetes who had baseline LDL-C levels of ≥70mg/dL. All patients were taking the maximum tolerated dose of statins or were not able to tolerate statins. Patients also had atherosclerotic cardiovascular disease or at least 1 other cardiovascular risk factor, according to the authors.
The primary endpoint of the study was the difference in LDL-C from baseline to week 24 and adverse events between cohorts.
The patients were randomized to receive an injection of alirocumab 75-mg or a placebo injection every 2 weeks. Patients in the treatment group with LDL-C levels of ≥70mg/dL at 8 weeks received a dose increase to 150-mg at week 12.
The investigators reported that at 24 weeks, treatment with alirocumab reduced LDL-C by 49% compared with placebo. The drug was also observed to improve other lipid parameters, according to the session.
Significantly, 80% of patients treated with alirocumab 75-mg achieved LDL-C target levels.
The researchers also found that administering alirocumab plus insulin was safe, as the incidence of adverse events was similar to placebo. Alirocumab was found to be well-tolerated overall and did not impact glucose control, the investigators reported.
The study also examined the effect of the drug on newer lipid parameters so the investigators could gain a better understanding of how alirocumab may affect atherogenic diabetic dyslipidemia.
“People with diabetes are at high cardiovascular risk, and dyslipidemia is a major risk factor for macrovascular complications,” said Lawrence Leiter, MD, associate scientist at Li Ka Shing Knowledge Institute at St. Michael’s Hospital in Toronto, and professor in the departments of medicine and nutritional sciences at the University of Toronto. “Despite the current standard of care for lipid lowering therapy, many individuals with diabetes have persistent lipid abnormalities resulting in increased residual cardiovascular risk. For people with diabetes, cardiovascular risk increases with advanced duration of diabetes, particularly in insulin-treated patients. The results of the ODYSSEY DM-Insulin study provide valuable information on the efficacy and safety of alirocumab in this high cardiovascular risk group and will help guide clinical decision-making beyond statin therapy.”
The investigators also presented findings from the ODYSSEY DM-Dyslipidemia study. The clinical trial evaluated the safety and efficacy of alirocumab versus standard treatment in patients with type 2 diabetes and mixed dyslipidemia, defined as elevations in non-HDL-C and triglyceride levels accompanied by low levels of HDL-C, according to the session. All patients included had high cardiovascular risk and non-HDL-C inadequately controlled by statins.
Included in the 24-week study were 413 patients with type 2 diabetes who were randomized to receive alirocumab 75-mg via auto-injector every 2 weeks or standard care. Patients in the treatment group who did not have adequate non-HDL-C reduction at 12 weeks follow-up then received alirocumab 150-mg.
The primary endpoint of the trial was the change of non-HDL-C from baseline to 24 weeks between cohorts, according to the session.
At 24 weeks, the investigators found that alirocumab reduced non-HDL-C by 32.5% compared with standard treatment. Patients treated with alirocumab were observed to have reductions in other lipid parameters compared with patients in the control group.
The investigators also reported that a majority of patients achieved target lipid levels on the 75-mg dose of alirocumab.
The drug was generally well-tolerated, as adverse events between the cohorts were similar. Additionally, treatment with alirocumab was not observed to impact glucose control.
“Cardiovascular disease is a significant cause of morbidity and mortality in people with type 2 diabetes,” said lead investigator Robert R. Henry, MD. “Mixed dyslipidemia is commonly present in these patients and further increases their cardiovascular risk. The ODYSSEY-DM-DYSLIPIDEMA study is the first trial that directly compares a PCSK9 Inhibitor with usual care in patients with T2DM diabetes who have lipid disturbances. The results of our study will assist clinicians in the management of mixed dyslipidemia, which is a persistent challenge in clinical practice, for patients with type 2 diabetes.”