Presenting the ODYSSEY DM-DYSLIPIDEMIA data, which involved patients with T2DM, Dr. Del Prato observed that alirocumab was “generally well tolerated” and did not affect HbA1c or fasting plasma glucose levels.
He presented new data from a prespecified analysis that looked at the subgroup of 72 patients who were randomized into an alirocumab (n = 48) or fenofibrate (n = 24) as usual care arm. Dr. Del Prato reminded the audience that the choice of usual treatment was decided by the study investigators prior to randomizing patients, and that other usual care treatments included in the study were ezetimibe, omega-3 fatty acids, nicotinic acid, or no lipid-lowering therapy.
As in the insulin study, the majority (63.6%) of patients treated with alirocumab remained on the starting dose of 75 mg every 2 weeks and did not need up-titration.
Changes in the percentage of non-HDL-C from baseline over time were greater in the alirocumab group than in the usual care group, both in the overall population and in the fenofibrate subanalysis.
Higher percentages of patients treated with alirocumab achieved non-HDL-C compared with those given usual care (66.9% vs. 17.7% in overall population, 65.2% vs. 10.1% in fenofibrate sub-analysis) and LDL-C (70.8% vs. 16.3% and 71.9% vs. 17.5%, respectively) goals at week 24.
Alirocumab also significantly reduced levels of Apo B, total cholesterol, and Lp(a) versus the overall usual care group and also versus the fenofibrate usual care group, Dr. Del Prato said.
Taking the two studies together, he concluded: “These data support alirocumab as a treatment option in people with diabetes mellitus and hypercholesterolemia despite maximally tolerated statins,” Dr. Del Prato said.
Will the lipid-benefits translate into improved cardiovascular outcomes?
The question now is whether the lipid-lowering effects of alirocumab in patients with diabetes will translate into improved cardiovascular outcomes in patients with diabetes.
The results of the ODYSSEY OUTCOMES trial, which is evaluating cardiovascular outcomes during treatment with alirocumab after an acute coronary syndrome, are expected next year. While the trial is not being conducted specifically in patients with diabetes, it is expected that there will be subpopulations of T1DM and T2DM patients included.
Cardiovascular outcomes data on the PCSK9 inhibitor, evolocumab (Repatha, Amgen) in the FOURIER trial were published in March (N Engl J Med 2017;376:1713-22) and provide some evidence that a reduction in major cardiovascular events may be possible with these agents.
Providing independent comment on the study, Angelo Avogaro, MD, of the University of Padova, Italy, said that the additional LDL-C lowering effect of alirocumab on top of statins could theoretically halve the projected 10-year risk of cardiovascular disease using data from the two ODYSSEY studies and the UKPDS Risk Engine. Using a baseline 10-year cardiovascular risk of around 26%-28%, this could be reduced to 11%-13%, he suggested.
Of note, Dr. Avogaro said, was that, at baseline, not all patients were on high intensity statins, the majority received moderate doses, with a good number of patients taking none or who were intolerant to statins included. “This, I like,” he observed.
A reassuring point was that there was no signal of having a detrimental effect on neurocognitive dysfunction, Dr. Avogaro observed, which concurs with recent data published on evolocumab (N Engl J Med 2017; 377:633-43).
Nevertheless, longer-follow-up is needed to examine adverse effects, “especially in those insulin-treated patients experiencing severe hypoglycemic reactions.”
The ODYSSEY DM studies were funded by Sanofi and Regeneron Pharmaceuticals.
Dr. Colhoun has received research grants from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Pfizer, Regeneron Pharmaceuticals, Roche Pharmaceuticals, and Sanofi. She has also been a consultant for Eli Lilly, Regeneron Pharmaceuticals, and Sanofi.
Dr. Del Prato has received research funding from AstraZeneca, Boehringer Ingelheim, Novartis, Merck Sharpe & Dohme, and Novo Nordisk. He is a consultant for or has received honoraria from the preceding companies, as well as from Eli Lilly, GlaxoSmithKline, Janssen Pharmaceuticals, Laboratoires Servier, Sanofi-Aventis, and Takeda Pharmaceuticals.