Evolocumab Lowers LDL-C in Diabetic Patients on Maximum Statins

By Marilynn Larkin

April 22, 2019

NEW YORK (Reuters Health) - In patients with type 2 diabetes and hyperlipidemia or mixed dyslipidemia on a maximally tolerated statin, treatment with evolocumab lowers low-density-lipoprotein cholesterol (LDL-C) and improves levels of other lipids, researchers say.

"BANTING was a trial of type 2 diabetes patients who received standard-of-care therapy including moderate-to-high-intensity statins and anti-diabetic treatment," Dr. Robert Rosenson of Icahn School of Medicine at Mount Sinai in New York City told Reuters Health by email. "There was an improvement in fasting lipids and no change in glucose, insulin or hemoglobin A1c. These results are consistent with previous studies."

Further, when participants were given a standardized meal, "the post-meal triglyceride remnants were reduced, which was an unexpected favorable finding," he said. "These findings are consistent with clearance of remnant particles by the LDL receptor."

Dr. Rosenson and colleagues' post-hoc analysis of the BANTING trial included 421 individuals randomized 2:1 to subcutaneous evolocumab, 420 mg monthly, or placebo.

Participants' mean age was 62, 44% were women and 77%, white. At baseline, their HbA1c was <10% (86 mmol/mol), they had been on stable anti-diabetic drug therapy for six months or longer, and they were taking a maximum-tolerated statin dose of at least moderate intensity. Lipid eligibility criteria varied by the individual's history of cardiovascular disease.

Coprimary endpoints were the mean percentage change in LDL-C from baseline to week 12 and to the mean of weeks 10 and 12.

As reported online April 5 in Diabetologia, evolocumab decreased LDL-C by 54.3% at week 12, versus a 1.1% decrease with placebo, and by 65% at the mean of weeks 10 and 12, versus an 0.8% decrease with placebo.

Evolocumab also decreased non-high-density-lipoprotein (HDL) cholesterol by 46.9% at week 12, versus a 0.6% decrease with placebo, and by 56.6% at the mean of weeks 10 and 12, versus a 0.1% decrease with placebo.

Further, according to the authors, evolocumab significantly improved levels of other lipids, enabling more participants to reach LDL-C <1.81 mmol/l or a reduction in LDL-C levels of 50% or more.

After a mixed-meal tolerance test, participants taking evolocumab experienced "favorable changes" in chylomicron triacylglycerol, chylomicron cholesterol, LDL-C and very low-density lipoprotein cholesterol.

As Dr. Rosenson noted, evolocumab had no effect on glycemic variables and was well tolerated.

"Patients who are prescribed PCSK9 inhibitors should be comforted that evolocumab will not worsen their glycemic risk and provide incremental benefit beyond that measured on fasting blood specimens," he concluded.

Endocrinologist and geriatrician Dr. Willy Valencia-Rodrigo of the Miami Veterans Affairs Medical Center told Reuters Health by email that the study results "enhance our experience and knowledge in lipid management, but at this moment do not change clinical practice. We would need a well-designed, large, long-term, multi-center clinical trial, with primary cardiovascular end-points and patient-centered outcomes. The design model would be comparative effectiveness (and) a cost-effectiveness study would likely follow."

"While randomization is a helpful tool to tease out baseline group characteristics, nutrition and obesity/type 2 diabetes state and management are major confounding variables when the outcomes include lipid metabolism," he noted. "Non-HDL-C could be highly dependent on the state of diabetes control and carbohydrate intake."

"This is a good opportunity to remind clinicians about periodic monitoring to avoid clinical inertia, adjusting targets and therapies, and thereby addressing potentially reversible abnormal lipid metabolism," he added. "We look forward to future studies that incorporate the control of nutrition, obesity and type 2 diabetes before and during the use of additional antihyperlipidemic pharmacologic agents."

Dr. Rajesh K. Garg, Director of the Comprehensive Diabetes Center at the University of Miami's Miller School of Medicine, also commented by email, "Evolocumab and other PCSK9 inhibitor drugs are a major advance in lipidology. These drugs have become an important part of the treatment algorithm for cardiovascular disease prevention and are likely to help millions of people."

"However, the cost of these drugs is prohibitory," he said by email. "Despite lowering the price of evolocumab to one-third of its original price, it still costs $5,850 per year. This increases disparity in healthcare. It is urgent that our society find a way to make important drugs affordable for everyone."

The study was funded by Amgen. Dr. Rosenson and another author have received funds from the company, one author is an employee and one was previously an employee.

SOURCE: http://bit.ly/2Gs6B1x

Diabetologia 2019.