ODYSSEY trials reveal positive effect of alirocumab on lipid profile in patients with T2D
The PCSK9* inhibitor alirocumab reduced low-density lipoprotein cholesterol (LDL-C) levels and several other lipid parameters in patients with type 2 diabetes (T2D) and high cardiovascular risk, according to two studies presented at the 77th Scientific Sessions of the American Diabetes Association (ADA 2017) held in San Diego, California, US.
“Despite the widespread availability of statins for many years, many individuals with diabetes still have persistent lipid abnormalities resulting in ... residual cardiovascular risk,” said Professor Lawrence Leiter from the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Canada, who presented the results of the ODYSSEY DM-INSULIN** trial.
“Alirocumab resulted in significant improvement in LDL-C levels as well as improvements in many other lipid parameters relative to placebo. Alirocumab was generally safe, well tolerated, and did not affect glycaemic measures,” he said.
Participants in the ODYSSEY DM-INSULIN trial were 441 adults with insulin-treated T2D, cardiovascular risk factors, and LDL-C levels ≥70 mg/dL inadequately controlled with maximum tolerated statin therapy or unable to tolerate statins who were randomized to receive alirocumab (75 mg injected Q2W; n=294) or placebo (n=147) for 24 weeks.
At 24 weeks, patients on alirocumab had a 49 percent reduction in LDL-C levels compared with patients on placebo (p<0.0001). [ADA 2017, session 1-AC-SY12]
At week 12, patients on alirocumab whose LDL-C levels were ≥70 mg/dL at 8 weeks had the option of a blinded dose increase to 150 mg; 80 percent of patients whose dose was maintained at 75 mg achieved recommended target LDL-C levels.
Patients on alirocumab also experienced reductions in other lipid parameters including non-high-density lipoprotein cholesterol (non-HDL-C; -38.7 percent), and Apo B (-36.7 percent; p<0.0001 for both vs placebo).
At week 24, 76.4 percent of patients on alirocumab achieved LDL-C <70 mg/dL, while 70.9 percent of patients on alirocumab achieved non-HDL-C <100 mg/dL.
In the ODYSSEY DM-DYSLIPIDEMIA*** trial, 413 patients with T2D with dyslipidaemia (non-HDL-C ≥100 mg/dL, triglycerides ≥150 – <500 mg/dL) and high cardiovascular risk, not adequately controlled with maximum tolerated dose of statin therapy, were randomized to alirocumab (75 mg Q2W; n=276) or standard of care (ezetimibe, fenofibrates, omega-3 fatty acids, nicotinic acid, or no additional lipid-lowering therapy; n=137) for 24 weeks.
At 24 weeks, patients on alirocumab had a 32.5 percent reduction in non-HDL-C levels compared with patients on standard of care (p<0.0001).
Non-HDL-C <100 mg/dL was achieved by 66.9 percent of patients on alirocumab compared with 17.7 percent of patients on standard of care, while LDL-C <70 mg/dL was achieved by 70.8 and 16.3 percent of patients on alirocumab and standard of care, respectively.
About 63 percent of patients on alirocumab achieved recommended lipid levels on the 75 mg dose.
Patients on alirocumab also achieved reductions in other lipid parameters such as LDL-C (-43 percent), Apo B (-32.3 percent), and total cholesterol (-24.6 percent; all p<0.0001 vs standard of care).
Alirocumab did not appear to affect glucose control and the incidence of adverse events was comparable between patients on alirocumab and placebo and alirocumab and standard of care in the ODYSSEY DM-INSULIN and ODYSSEY DM-DYSLIPIDEMIA trials, respectively.
“Mixed dyslipidaemia, manifested as an increase in non-HDL-C, elevated triglycerides, lower HDL, and often elevations of LDL-C, is commonly present in patients with T2D and further increases the cardiovascular risk. Management of mixed dyslipidaemia is a persistent challenge in clinical practice,” said Professor Robert Henry from the University of California San Diego School of Medicine, San Diego, California, US, who presented the findings of the ODYSSEY DM-DYSLIPIDEMIA trial.
“Alirocumab [was] superior vs usual care in reducing non-HDL-C after 24 weeks and improved many other lipid parameters better than usual care,” he said.