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Aim: To examine the efficacy of 12 weeks of monthly evolocumab (EvoMab) 420 mg vs. placebo (Pbo) in lowering LDL-C in those with type 2 diabetes mellitus (T2DM) and hypercholesterolemia or mixed dyslipidemia and on statin therapy.

Methods: Patients ≥18 years with T2DM, HbA1c <10%, on stable pharmacotherapy for diabetes for ≥6 months, and taking a statin were eligible; 421 were randomized (2:1 EvoMab:Pbo) and dosed. Co-primary endpoints: mean % change in LDL-C from baseline to week 12 and mean % change in LDL-C from baseline to the mean of weeks 10 and 12. Additional measures included change in non-HDL-C, LDL-C goals, and measures of glycemic control.

Results: Mean participant age (SD) was 62 (8) years; 44% women; 77% Caucasian. In modified, intent to treat analyses (all randomized and dosed patients) EvoMab significantly reduced LDL-C and non-HDL-C vs. Pbo, and did not impact glycemic control. The incidence of AEs was comparable between EvoMab and Pbo, with no clinically meaningful differences in serious AEs. See Table.

Table.

 Placebo(N=141) Evolocumab(N=280) 
Baseline LDL-C (mg/dL), mean (SD) 110.4 (33.0) 108.6 (31.0) 
Baseline non-HDL-C (mg/dL), mean (SD) 145.5 (33.9) 144.6 (34.9) 
Any adverse event (AE), n (%) 52 (36.9) 110 (39.3) 
Serious AE, n (%) 2 (1.4) 14 (5.0) 14 (5.0)14 (5.0)a 
Mean of Weeks 10 and 12   
Lipids Percent change from baseline in LDL-C, mean (SE) –0.8 (1.8) –65.0 (1.3)b 
 Percent change from baseline in non-HDL-C, mean (SE) –0.(1.6) –56.6 (1.2)b 
 Achievement of LDL-C < 70 mg/dL, n, % 20 (14.8) 253 (92.7)b 
 Achievement of ≥50% reduction in LDL-C, n, % 1 (0.7) 230 (84.2)b 
Week 12    
Glycemic Control Change from baseline in FSG in mg/dL, median (Q1, Q3) 4.0(–15.0, 29.0) 5.0(–13.5, 29.5) 
 Change from baseline in HbA1c in percent, median (Q1, Q3) 0.1(–0.2, 0.5) 0.1(–0.2, 0.5) 
 Placebo(N=141) Evolocumab(N=280) 
Baseline LDL-C (mg/dL), mean (SD) 110.4 (33.0) 108.6 (31.0) 
Baseline non-HDL-C (mg/dL), mean (SD) 145.5 (33.9) 144.6 (34.9) 
Any adverse event (AE), n (%) 52 (36.9) 110 (39.3) 
Serious AE, n (%) 2 (1.4) 14 (5.0) 14 (5.0)14 (5.0)a 
Mean of Weeks 10 and 12   
Lipids Percent change from baseline in LDL-C, mean (SE) –0.8 (1.8) –65.0 (1.3)b 
 Percent change from baseline in non-HDL-C, mean (SE) –0.(1.6) –56.6 (1.2)b 
 Achievement of LDL-C < 70 mg/dL, n, % 20 (14.8) 253 (92.7)b 
 Achievement of ≥50% reduction in LDL-C, n, % 1 (0.7) 230 (84.2)b 
Week 12    
Glycemic Control Change from baseline in FSG in mg/dL, median (Q1, Q3) 4.0(–15.0, 29.0) 5.0(–13.5, 29.5) 
 Change from baseline in HbA1c in percent, median (Q1, Q3) 0.1(–0.2, 0.5) 0.1(–0.2, 0.5) 

aNo pattern in differences in serious AEs was observed. Chronic obstructive pulmonary disease was the only serious AE reported by ≥ 1% of patients in the evolocumab treatment group.

bP < 0.0001 for evolocumab versus placebo comparison

FSG, fasting serum glucose; HbA1c, glycated hemoglobin; LDL-C, low-density lipoprotein cholesterol; non-HDL-C, non-high-density lipoprotein cholesterol; SE, standard error

Funding: Amgen Inc.

Conclusion: In statin-treated patients with T2DM and hypercholesterolemia or mixed dyslipidemia, evolocumab safely and effectively lowered LDL-C.

Disclosure

R.S. Rosenson: Other Relationship; Self; Akcea Therapeutics, Amgen Inc., AstraZeneca, Eli Lilly and Company, The Medicines Company, Regeneron Pharmaceuticals, Inc., Sanofi US, Kowa Pharmaceuticals America, Inc., UpToDate. M.L. Daviglus: Advisory Panel; Self; Amgen Inc. P. Reaven: Research Support; Self; AstraZeneca, Amgen Inc., Bristol-Myers Squibb Company. P. Pozzilli: Research Support; Self; Sanofi. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; Merck Sharp & Dohme Corp. H. Bays: Research Support; Self; Amgen Inc. M. Monsalvo: Employee; Self; Amgen Inc.. Stock/Shareholder; Self; Amgen Inc. M. Elliott: Employee; Self; Amgen Inc.. Stock/Shareholder; Self; Amgen Inc. R. Somaratne: Employee; Self; NGM Biopharmaceuticals. Stock/Shareholder; Self; NGM Biopharmaceuticals. Y. Handelsman: Consultant; Self; Amarin Corporation. Speaker's Bureau; Self; Amarin Corporation. Board Member; Self; American Association of Clinical Endocrinologists. Consultant; Self; Amgen Inc.. Research Support; Self; Amgen Inc.. Speaker's Bureau; Self; Amgen Inc.. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Gan & Lee Pharmaceuticals. Consultant; Self; Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; Lexicon Pharmaceuticals, Inc.. Consultant; Self; Merck & Co., Inc.. Research Support; Self; Merck & Co., Inc.. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc., Regeneron Pharmaceuticals, Inc.. Consultant; Self; Sanofi. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi.

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