medwireNews: Data from the ODYSSEY series of trials, presented at the American Diabetes Association scientific sessions, show that the PCSK9 inhibitor alirocumab reduces atherogenic dyslipidemia in patients with diabetes.
Five presenters revealed data for the ODYSSEY DM-INSULIN and DM-DYSLIPIDEMIA trials, which were randomized trials testing the effects of alirocumab in type 2 diabetes patients using insulin and with mixed dyslipidemia, respectively.
Opening the session, Kausik Ray (Imperial College London, UK) explained that diabetes patients have increased levels of the smallest, most atherogenic lipid particles, reflected in a high level of non-high-density lipoprotein (HDL) cholesterol. He said that patients with this type of atherogenic dyslipidemia struggle to meet their lipid targets, even with treatment such as statins, but evidence suggests that PCSK9 inhibition may be more effective in these patients.
In addition, Bertrand Cariou (L’institut du Throrax, Nantes, France) noted that there is as yet no evidence that PCSK9 inhibitors affect glucose metabolism or increase diabetes risk, despite genetic studies predicting such an effect.
Dirk Muller-Wieland (University Hospital Aachen, Germany) outlined the ODYSSEY study designs, noting in particular that ODYSSEY DM-DYSLIPIDEMIA is the first trial of a PCSK9 inhibitor in patients with mixed dyslipidemia to have a primary endpoint of change in non-HDL cholesterol.
In both trials, alirocumab was given every second week, at a starting dose of 75 mg, rising to 150 mg at week 12 if patients had not achieved their lipid target (low-density lipoprotein cholesterol ≤70 mg/dL) by week 8 – this only proved necessary in a third of patients. The patients had either overt atherosclerotic disease or cardiovascular risk factors, and were above their lipid targets at baseline despite most taking moderate- or high-intensity statins.
ODYSSEY DM-INSULIN included patients with type 1 and type 2 diabetes; Lawrence Leiter (University of Toronto, Ontario, Canada) presented the results for those with type 2 diabetes, comprising 294 randomly assigned to receive alirocumab and 147 assigned to the placebo group. The patients had been taking insulin for 5 to 6 years.
The primary endpoint in this trial, of reduction in low-density lipoprotein (LDL) cholesterol at 24 weeks, was an average of 49% with alirocumab versus placebo, similar to that previously reported in patients without diabetes. Around three-quarters of patients achieved their LDL cholesterol targets.
Patients in ODYSSEY DM-DYSLIPIDEMIA were not necessarily insulin-treated, although around 40% were using it. Robert Henry (University of California, San Diego, USA) reported that 276 patients were assigned to receive alirocumab and 137 to usual care.
The patients in the alirocumab and usual care groups had starting non-HDL cholesterol levels of 155.1 and 161.5 mg/dL, respectively. During 24 weeks of treatment these fell by a respective 37.3% and 4.7%, equating to a significant 32.5% difference between the groups. A corresponding 66.9% and 17.7% of patients achieved their non-HDL cholesterol target of less than 100 mg/dL, and 70.8% versus 16.3% achieved LDL cholesterol below 70 mg/dL.
In neither trial did the researchers see evidence of increased glycated hemoglobin, fasting plasma glucose, insulin dose, or need for other diabetes medications.
Adverse events were similar between treatment groups. In ODYSSEY DM-INSULIN there was an elevated risk for adverse events leading to discontinuation in the alirocumab group, but this was not seen in ODYSSEY DM-DYSLIPIDEMIA.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2017 Springer Healthcare part of the Springer Nature group