TY - JOUR
T1 - Efficacy and safety of evolocumab in individuals with type 2 diabetes mellitus
T2 - primary results of the randomised controlled BANTING study
AU - Rosenson, Robert S.
AU - Daviglus, Martha L.
AU - Handelsman, Yehuda
AU - Pozzilli, Paolo
AU - Bays, Harold
AU - Monsalvo, Maria Laura
AU - Elliott-Davey, Mary
AU - Somaratne, Ransi
AU - Reaven, Peter
N1 - Funding Information:
Conclusions/interpretation In statin-treated individuals with type 2 diabetes and hypercholesterolaemia or mixed dyslipidaemia, evolocumab significantly reduced LDL-C and non-HDL-C. Favourable changes (p < 0.05) were observed in postprandial levels of chylomicrons, VLDL-C and LDL-C. Trial registration ClinicalTrials.gov NCT02739984 Funding This study was funded by Amgen Inc. Data availability Qualified researchers may request data from Amgen clinical studies. Complete details are available at www. amgen.com/datasharing.
Funding Information:
The authors acknowledge A. M. Nawrocki of Amgen Inc. for providing editorial support and Ellen Bradley of Amgen Ltd. for providing statistical support. Some of the data from this manuscript was presented, in part, at the ADA 78th Scientific Sessions in Orlando, June 2018. Site investigators by country are listed in the ESM.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Aims/hypothesis: The study aimed to examine the efficacy of 12 weeks of monthly evolocumab or placebo in lowering LDL-cholesterol (LDL-C) in individuals with type 2 diabetes and hypercholesterolaemia or mixed dyslipidaemia and on a maximum-tolerated statin of at least moderate intensity. Methods: For this randomised, placebo-controlled outpatient study, eligible individuals were ≥18 years old with type 2 diabetes, HbA 1c <10% (86 mmol/mol), had been on stable pharmacological therapy for diabetes for ≥6 months and were taking a maximum-tolerated statin dose of at least moderate intensity. Lipid eligibility criteria varied by history of clinical cardiovascular disease. Participants were randomised 2:1 to evolocumab 420 mg s.c. or placebo. Randomisation was performed centrally via an interactive web-based or voice recognition system. Allocation was concealed using the centralised randomisation process. Treatment assignment was blinded to the sponsor study team, investigators, site staff and patients throughout the study. Co-primary endpoints were mean percentage change in LDL-C from baseline to week 12 and to the mean of weeks 10 and 12. Additional endpoints included LDL-C <1.81 mmol/l, LDL-C reduction ≥50% and other lipids. Exploratory analyses included percentage changes in fasting and post mixed-meal tolerance test (MMTT) lipoproteins and lipids, glucose metabolism variables and inflammatory biomarkers. Results: In total, 421 individuals were randomised and analysed, having received evolocumab (280 participants) or placebo (141 participants) (mean [SD] age 62 [8] years; 44% women; 77% white). Evolocumab decreased LDL-C by 54.3% (1.4%) at week 12 (vs 1.1% [1.9%] decrease with placebo; p < 0.0001) and by 65.0% (1.3%) at the mean of weeks 10 and 12 (vs 0.8% [1.8%] decrease with placebo; p < 0.0001); it also decreased non-HDL-cholesterol (HDL-C) by 46.9% (1.3%) at week 12 (vs 0.6% [1.8%] decrease with placebo) and by 56.6% (1.2%) at the mean of weeks 10 and 12 (vs 0.1% [1.6%] decrease with placebo). Evolocumab significantly improved levels of other lipids and allowed more participants to reach LDL-C <1.81 mmol/l or a reduction in LDL-C levels ≥50%. After an MMTT (120 min), there were favourable changes (p < 0.05; nominal, post hoc, no multiplicity adjustment) in chylomicron triacylglycerol (triglycerides), chylomicron cholesterol, VLDL-C and LDL-C. Evolocumab had no effect on glycaemic variables and was well tolerated. Conclusions/interpretation: In statin-treated individuals with type 2 diabetes and hypercholesterolaemia or mixed dyslipidaemia, evolocumab significantly reduced LDL-C and non-HDL-C. Favourable changes (p < 0.05) were observed in postprandial levels of chylomicrons, VLDL-C and LDL-C. Trial registration: ClinicalTrials.gov NCT02739984 Funding: This study was funded by Amgen Inc. Data availability: Qualified researchers may request data from Amgen clinical studies. Complete details are available at www.amgen.com/datasharing.
AB - Aims/hypothesis: The study aimed to examine the efficacy of 12 weeks of monthly evolocumab or placebo in lowering LDL-cholesterol (LDL-C) in individuals with type 2 diabetes and hypercholesterolaemia or mixed dyslipidaemia and on a maximum-tolerated statin of at least moderate intensity. Methods: For this randomised, placebo-controlled outpatient study, eligible individuals were ≥18 years old with type 2 diabetes, HbA 1c <10% (86 mmol/mol), had been on stable pharmacological therapy for diabetes for ≥6 months and were taking a maximum-tolerated statin dose of at least moderate intensity. Lipid eligibility criteria varied by history of clinical cardiovascular disease. Participants were randomised 2:1 to evolocumab 420 mg s.c. or placebo. Randomisation was performed centrally via an interactive web-based or voice recognition system. Allocation was concealed using the centralised randomisation process. Treatment assignment was blinded to the sponsor study team, investigators, site staff and patients throughout the study. Co-primary endpoints were mean percentage change in LDL-C from baseline to week 12 and to the mean of weeks 10 and 12. Additional endpoints included LDL-C <1.81 mmol/l, LDL-C reduction ≥50% and other lipids. Exploratory analyses included percentage changes in fasting and post mixed-meal tolerance test (MMTT) lipoproteins and lipids, glucose metabolism variables and inflammatory biomarkers. Results: In total, 421 individuals were randomised and analysed, having received evolocumab (280 participants) or placebo (141 participants) (mean [SD] age 62 [8] years; 44% women; 77% white). Evolocumab decreased LDL-C by 54.3% (1.4%) at week 12 (vs 1.1% [1.9%] decrease with placebo; p < 0.0001) and by 65.0% (1.3%) at the mean of weeks 10 and 12 (vs 0.8% [1.8%] decrease with placebo; p < 0.0001); it also decreased non-HDL-cholesterol (HDL-C) by 46.9% (1.3%) at week 12 (vs 0.6% [1.8%] decrease with placebo) and by 56.6% (1.2%) at the mean of weeks 10 and 12 (vs 0.1% [1.6%] decrease with placebo). Evolocumab significantly improved levels of other lipids and allowed more participants to reach LDL-C <1.81 mmol/l or a reduction in LDL-C levels ≥50%. After an MMTT (120 min), there were favourable changes (p < 0.05; nominal, post hoc, no multiplicity adjustment) in chylomicron triacylglycerol (triglycerides), chylomicron cholesterol, VLDL-C and LDL-C. Evolocumab had no effect on glycaemic variables and was well tolerated. Conclusions/interpretation: In statin-treated individuals with type 2 diabetes and hypercholesterolaemia or mixed dyslipidaemia, evolocumab significantly reduced LDL-C and non-HDL-C. Favourable changes (p < 0.05) were observed in postprandial levels of chylomicrons, VLDL-C and LDL-C. Trial registration: ClinicalTrials.gov NCT02739984 Funding: This study was funded by Amgen Inc. Data availability: Qualified researchers may request data from Amgen clinical studies. Complete details are available at www.amgen.com/datasharing.
KW - Diabetes
KW - Diabetic dyslipidaemia
KW - Hypercholesterolaemia
KW - Lipid-lowering therapy
KW - PCSK9 inhibition
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U2 - 10.1007/s00125-019-4856-7
DO - 10.1007/s00125-019-4856-7
M3 - Article
C2 - 30953107
AN - SCOPUS:85064203868
SN - 0012-186X
VL - 62
SP - 948
EP - 958
JO - Diabetologia
JF - Diabetologia
IS - 6
ER -