Adults with type 2 diabetes randomly assigned the PCSK9 inhibitor Repatha saw a 60% reduction in LDL cholesterol during 12 weeks vs. those assigned placebo, a rate similar to patients without type 2 diabetes, according to a recent meta-analysis.
“[Repatha] has promising efficacy and short-term safety in patients with type 2 diabetes,” Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow, Scotland, told Endocrine Today. “This will give clinicians who wish to consider PCSK9 inhibitors for their diabetes patients some comfort in their prescribing, at least in terms of likely achieved LDL cholesterol levels.”
Sattar and colleagues analyzed individual patient data from three 12-week randomized controlled trials comparing the efficacy of Repatha (evolocumab, Amgen), Zetia (ezetimibe, Merck) and placebo in adults with and without type 2 diabetes. Within the cohort, 413 patients had type 2 diabetes (246 assigned evolocumab; 73 assigned ezetimibe; 94 assigned placebo); 2,119 patients did not have diabetes (1,296 assigned evolocumab; 250 assigned ezetimibe; 573 assigned placebo).
Researchers used random-effects models to compare mean changes from baseline in concentrations of LDL, non-HDL, total cholesterol, triglycerides, lipoprotein(a) and HDL at 12 weeks, and they assessed the effect of evolocumab vs. placebo across subgroups based on glycemia, insulin use, renal function and cardiovascular disease status at baseline.
After 12 weeks, mean changes in LDL with evolocumab were similar in patients with and without type 2 diabetes, with greater reductions with evolocumab vs. placebo (60%; 95% CI, 51-69 for patients with diabetes, and 66%; 95% CI, 62-70, for those without) and evolocumab vs. ezetimibe (39%; 95% CI, 32-47 for patients with diabetes, and 40%; 95% CI, 36-45, for those without).
Patients with type 2 diabetes assigned evolocumab also saw a 55% reduction in non-HDL vs. placebo (95% CI, 47-63) and a 34% reduction vs. ezetimibe (95% CI, 26-41); a 38% reduction in total cholesterol vs. placebo (95% CI, 32-44) and a 24% reduction vs. ezetimibe (95% CI, 16-31); a 31% reduction in lipoprotein(a) vs. placebo (95% CI, 25-37) and a 26% reduction vs. ezetimibe (95% CI, 16-35), and an increase in HDL (7% vs. placebo and 8% vs. ezetimibe).
Findings were similar across diabetes subgroups based on glycemia, insulin use, renal function, and CVD status, according to researchers.
“We need to see the results from ongoing [CV] outcome trials of PCSK9 inhibitors to fully understand the benefits and longer-term safety aspects, and only from such data can guideline committees better recommend which patients with diabetes should be recommended for PCSK9 inhibitors,” Sattar said. “Initially, it will be likely that diabetes patients with established or progressive CVD and with sustained high LDL cholesterol levels despite maximally tolerated statin or ezetimibe may be targeted for PCSK9 inhibitors. Each country/body will have to determine their own criteria.” – by Regina Schaffer
For more information:
Naveed Sattar, PhD,
can be reached at University of Glasgow, Glasgow G12 8QQ, United Kingdom; email: Naveed.Sattar@glasgow.ac.uk.
All studies were funded by Amgen. Sattar reports receiving consulting fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Merck, and grant support through his institution from Amgen and AstraZeneca. Please see the full study for the other authors’ relevant financial disclosures.