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.
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.
