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

Media type: E-Article
Title: Relation of Lipoprotein(a) Levels to Incident Type 2 Diabetes and Modification by Alirocumab Treatment
Contributor: 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; Schwartz, Gregory G.; Steg, Philippe Gabriel; Bhatt, Deepak L.; Bittner, Vera A.; Diaz, Rafael; Goodman, Shaun G.; Harrington, Robert A.; Jukema, J. Wouter; Szarek, Michael; White, Harvey D.; Zeiher, Andreas M.; Tricoci, Pierluigi; [...]
Published: American Diabetes Association, 2021
Published in: Diabetes Care
Extent: 1219-1227
Language: English
DOI: 10.2337/dc20-2842
ISSN: 0149-5992; 1935-5548
Keywords: Advanced and Specialized Nursing ; Endocrinology, Diabetes and Metabolism ; Internal Medicine
Abstract: <jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>RESEARCH DESIGN AND METHODS</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>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, P &lt; 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 P = 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; P = 0.0002) for incident type 2 diabetes.</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>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.</jats:p> </jats:sec>
Description: <jats:sec>
<jats:title>OBJECTIVE</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>RESEARCH DESIGN AND METHODS</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>RESULTS</jats:title>
<jats:p>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, P &lt; 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 P = 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; P = 0.0002) for incident type 2 diabetes.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>CONCLUSIONS</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
Footnote:
Access State: Open Access

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