Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment

• Published in: Diabetes care Vol. 44; no. 5; pp. 1219 - 1227
• Main Authors: Schwartz, Gregory G, Szarek, Michael, Bittner, Vera A, Bhatt, Deepak L, Diaz, Rafael, Goodman, Shaun G, Jukema, J Wouter, Loy, Megan, Manvelian, Garen, Pordy, Robert, White, Harvey D, Steg, Philippe Gabriel
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.05.2021
• Subjects: Acute coronary syndromes; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Cardiology and cardiovascular system; Cardiovascular and Metabolic Risk; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; Double-Blind Method; Endocrinology and metabolism; Health hazards; Human health and pathology; Humans; Life Sciences; Lipoprotein(a); Lipoproteins; Medication; Monoclonal antibodies; Pharmaceutical sciences; Proprotein Convertase 9; Research design; Treatment Outcome
• ISSN: 0149-5992; 1935-5548; 1935-5548; 0149-5992
• DOI: 10.2337/dc20-2842

In observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor. In the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data. Among 13,480 patients without diabetes at baseline, 1,324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02-1.06, < 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85-1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment-baseline lipoprotein(a) interaction = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03-1.12; = 0.0002) for incident type 2 diabetes. In patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment-related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined.