PMID- 30953107 OWN - NLM STAT- MEDLINE DCOM- 20200113 LR - 20221124 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 62 IP - 6 DP - 2019 Jun TI - Efficacy and safety of evolocumab in individuals with type 2 diabetes mellitus: primary results of the randomised controlled BANTING study. PG - 948-958 LID - 10.1007/s00125-019-4856-7 [doi] 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 . FAU - Rosenson, Robert S AU - Rosenson RS AD - Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, MC Level, New York, NY, 10029, USA. robert.rosenson@mssm.edu. FAU - Daviglus, Martha L AU - Daviglus ML AD - University of Illinois at Chicago College of Medicine, Chicago, IL, USA. FAU - Handelsman, Yehuda AU - Handelsman Y AD - Metabolic Institute of America, Tarzana, CA, USA. FAU - Pozzilli, Paolo AU - Pozzilli P AD - University Campus Bio-medico, Rome, Italy. FAU - Bays, Harold AU - Bays H AD - Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY, USA. FAU - Monsalvo, Maria Laura AU - Monsalvo ML AD - Amgen Inc., Thousand Oaks, CA, USA. FAU - Elliott-Davey, Mary AU - Elliott-Davey M AD - Amgen Ltd, Cambridge, UK. FAU - Somaratne, Ransi AU - Somaratne R AD - Amgen Inc., Thousand Oaks, CA, USA. FAU - Reaven, Peter AU - Reaven P AD - University of Arizona College of Medicine, Phoenix VA Health Care System, Phoenix, AZ, USA. LA - eng SI - ClinicalTrials.gov/NCT02739984 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190405 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Anticholesteremic Agents) RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - LKC0U3A8NJ (evolocumab) SB - IM MH - Aged MH - Antibodies, Monoclonal, Humanized/*therapeutic use MH - Anticholesteremic Agents/*therapeutic use MH - Cholesterol, LDL/blood MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Female MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use MH - Hypercholesterolemia/blood/*drug therapy MH - Male MH - Middle Aged PMC - PMC6509076 OTO - NOTNLM OT - Diabetes OT - Diabetic dyslipidaemia OT - Hypercholesterolaemia OT - Lipid-lowering therapy OT - PCSK9 inhibition EDAT- 2019/04/07 06:00 MHDA- 2020/01/14 06:00 PMCR- 2019/04/05 CRDT- 2019/04/07 06:00 PHST- 2018/11/20 00:00 [received] PHST- 2019/02/18 00:00 [accepted] PHST- 2019/04/07 06:00 [pubmed] PHST- 2020/01/14 06:00 [medline] PHST- 2019/04/07 06:00 [entrez] PHST- 2019/04/05 00:00 [pmc-release] AID - 10.1007/s00125-019-4856-7 [pii] AID - 4856 [pii] AID - 10.1007/s00125-019-4856-7 [doi] PST - ppublish SO - Diabetologia. 2019 Jun;62(6):948-958. doi: 10.1007/s00125-019-4856-7. Epub 2019 Apr 5.