SAN DIEGO – The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab helped correct dyslipidemia but did not improve glucose control in patients with type 2 diabetes mellitus, investigators reported at the annual scientific sessions of the American Diabetes Association.
In the international, double-blind ODYSSEY DM-Insulin trial, 24 weeks of alirocumab (Praluent, Sanofi and Regeneron) therapy cut low-density lipoprotein (LDL) cholesterol levels by an average of 49% more than placebo (P less than .0001), said Lawrence A. Leiter, MD, professor of medicine and nutritional sciences at the University of Toronto. Alirocumab also significantly reduced non–high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) levels. However, hemoglobin A1c, fasting plasma glucose, total insulin dose, and number of antihyperglycemic drugs remained nearly identical between the trial arms throughout follow-up.
Dr. Lawrence A. Leiter
About 94% of patients in each arm completed the trial. Most were in their mid-60s, white, obese, and already on a moderate or high-intensity statin, with baseline fasting plasma glucose levels of about 150 mg per dL and HbA1c levels of 7.5%. The most common treatment-associated adverse events were myalgia (4%) and arthralgia (3%). Rates of local and systemic allergic drug reactions, neurologic or neurocognitive events, and elevated transaminases were low and similar between groups, according to Dr. Leiter, who is also director of the lipid clinic at the Li Ka Shing Knowledge Institute at St. Michael’s Hospital.
Robert R. Henry, MD, who is professor of medicine at the University of California, San Diego, discussed the ODYSSEY DM-Dyslipidemia trial which compared alirocumab with usual care in patients with type 2 diabetes whose mixed dyslipidemia was inadequately controlled with maximum tolerable statin therapy. In all, 413 patients received open-label alirocumab (75 mg–150 mg) or placebo plus optional ezetimibe, fenofibrate, omega-3 fatty acids, or nicotinic acid every 2 weeks for 24 weeks. At the end of treatment, non-HDL cholesterol dropped about 33% more with alirocumab than usual care (P less than .0001). Alirocumab also produced significant declines in LDL cholesterol, apolipoprotein B, total cholesterol, and lipoprotein(a), and a 6% increase in HDL cholesterol as compared with usual care. Once again, alirocumab induced no changes in HbA1c or fasting plasma glucose levels. The most common treatment-related adverse events were urinary tract infections, diarrhea, and nasopharyngitis.
Dr. Robert R. Henry
Sanofi US and Regeneron Pharmaceuticals make alirocumab and funded the trials. Dr. Leiter disclosed research grants and consulting relationships with Regeneron, Sanofi, Eli Lilly and Company, and several other pharmaceutical companies. Dr. Henry disclosed consulting and advisory relationships with Sanofi and many other pharmaceutical companies.