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In: Diabetes Care, American Diabetes Association, Vol. 44, No. 5 ( 2021-05-01), p. 1219-1227

Abstract: 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. RESEARCH DESIGN AND METHODS 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. RESULTS 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. CONCLUSIONS 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.

Type of Medium: Online Resource

ISSN: 0149-5992 , 1935-5548

URL: Article

DOI: 10.2337/dc20-2842

Language: English

Publisher: American Diabetes Association

Publication Date: 2021

detail.hit.zdb_id: 1490520-6

In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)

Abstract: Background: People with diabetes and recent ACS are at higher risk for ischemic CV events and derive greater benefit from intensive lipid-lowering therapy than those without diabetes. Effect of PCSK9 inhibition in patients with recent ACS and diabetes is unknown. Methods: Alirocumab (ALI) is a fully human monoclonal antibody to PCSK9. In ODYSSEY OUTCOMES, 18,924 patients with recent ACS and LDL-C≥70mg/dL on a maximum-tolerated dose of atorvastatin or rosuvastatin were randomly assigned to ALI 75mg or placebo SC every 2 weeks. ALI blindly increased to 150mg or decreased to placebo to achieve an LDL-C of 25-50mg/dL. Primary efficacy endpoint was time to first MACE: CHD death, nonfatal MI, ischemic stroke or hospitalization for unstable angina. This prespecified analysis reports efficacy and safety by baseline glucometabolic status, including new-onset diabetes (NOD). Results: Table reports incidence of MACE by assigned treatment and baseline glucometabolic status. Overall ALI reduced MACE, without evidence of effect modification by baseline glucometabolic status: a greater absolute risk reduction was observed with ALI in those with diabetes. NOD was not increased with ALI. Conclusion: Patients with recent ACS and diabetes derived greater absolute benefit from ALI added to maximum-tolerated statin. No increase in NOD was seen with ALI (NCT01663402).CategoryN (% of cohort)ARRHazard ratio (95% CI)PinteractionMACE cumulative incidenceAlirocumab n/N (%)Placebo n/N (%)All subjects18,924 (100)903/9462 (9.5)1052/9462 (11.1)1.60.85 (0.78, 0.93)NADiabetes5444 (28.8)380/2693 (14.1)452/2751 (16.4)2.30.84 (0.74, 0.97)0.98 Prediabetes8246 (43.6)331/4130 (8.0)380/4116 (9.2)1.20.86 (0.74, 1.00)Normoglycemia5234 (27.7)192/2639 (7.3)220/2595 (8.5)1.20.85 (0.70, 1.03)Median follow-up: 34 months. ARR, absolute risk reduction; NA, not applicable. Disclosure K.K. Ray: Consultant; Self; Amgen Inc., Sanofi. Research Support; Self; Sanofi. Consultant; Self; The Medicines Company. Research Support; Self; Amgen Inc., Regeneron Pharmaceuticals, Inc.. Consultant; Self; Regeneron Pharmaceuticals, Inc., Pfizer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., AstraZeneca, Esperion Therapeutics, Kowa Pharmaceuticals America, Inc.. Research Support; Self; Pfizer Inc.. Consultant; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Merck Sharp & Dohme Corp. H. Colhoun: Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH. Stock/Shareholder; Self; Bayer AG. Research Support; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Eli Lilly and Company. Other Relationship; Self; Eli Lilly and Company. Advisory Panel; Self; Novartis Pharmaceuticals Corporation. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Advisory Panel; Self; Regeneron Pharmaceuticals, Inc.. Speaker's Bureau; Self; Regeneron Pharmaceuticals, Inc.. Other Relationship; Self; Regeneron Pharmaceuticals, Inc.. Research Support; Self; Pfizer Inc., Roche Pharma. Stock/Shareholder; Self; Roche Pharma. Research Support; Self; Sanofi-Aventis. Advisory Panel; Self; Sanofi-Aventis. Speaker's Bureau; Self; Sanofi. Other Relationship; Self; Sanofi. Research Support; Self; Novo Nordisk Inc. M. Szarek: Consultant; Self; Sanofi, Regeneron Pharmaceuticals, Inc., Baxter, Resverlogix Corp. M. Baccara-Dinet: Employee; Self; Sanofi. D.L. Bhatt: Research Support; Self; Amarin Corporation, Amgen Inc., AstraZeneca, Bristol-Myers Squibb Company, Chiesi USA, Inc., Eisai Inc., Ethicon US, LLC., Forest Laboratories, Inc., Ironwood Pharmaceuticals, Inc., Ischemix, Eli Lilly and Company, Medtronic, Pfizer Inc., Roche Pharma, Sanofi-Aventis, The Medicines Company. Other Relationship; Self; American Heart Association. V. Bittner: Research Support; Self; AstraZeneca, Sanofi, Bayer AG, Esperion Therapeutics, Amgen Inc.. Advisory Panel; Self; Sanofi. Research Support; Self; Dalcor. A.J. Budaj: Other Relationship; Self; Sanofi-Aventis, AstraZeneca, Pfizer Inc., GlaxoSmithKline plc.. Consultant; Self; Bayer AG. Other Relationship; Self; Novartis Pharma K.K., Eisai Co., Ltd.. R. Diaz: None. S.G. Goodman: Research Support; Self; Amgen Inc.. Consultant; Self; Amgen Inc.. Research Support; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; Bayer AG. Consultant; Self; Bayer AG. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Bristol-Myers Squibb Company. Consultant; Self; Bristol-Myers Squibb Company. Research Support; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; GlaxoSmithKline plc.. Consultant; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation. Research Support; Self; Pfizer Inc.. Consultant; Self; Pfizer Inc.. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Consultant; Self; Regeneron Pharmaceuticals, Inc.. Research Support; Self; CSL Behring. C.G. Hanotin: Employee; Self; Sanofi. J. Jukema: Research Support; Self; Sanofi-Aventis, Regeneron Pharmaceuticals, Inc., Amgen Inc. V. Loizeau: Employee; Self; Sanofi. R.D. Lopes: Consultant; Self; Bayer AG, Boehringer Ingelheim GmbH. Other Relationship; Self; Bristol-Myers Squibb Company. Consultant; Self; Daiichi Sankyo Company, Limited. Other Relationship; Self; GlaxoSmithKline plc., Medtronic. Consultant; Self; Merck & Co., Inc.. Other Relationship; Self; Pfizer Inc. A. Moryusef: Employee; Self; Sanofi. R. Pordy: Employee; Self; Regeneron Pharmaceuticals, Inc.. A.D. Ristic: None. M. Roe: None. J. Tuñón: Speaker's Bureau; Self; Sanofi-Aventis. Advisory Panel; Self; Sanofi-Aventis. Other Relationship; Self; Sanofi-Aventis. Speaker's Bureau; Self; Amgen Inc. H.D. White: Other Relationship; Self; AstraZeneca, Eli Lilly and Company. Research Support; Self; National Institute for Health and Clinical Excellence. Other Relationship; Self; Omthera Pharmaceuticals, Inc., Pfizer Inc., Eisai Inc.. Research Support; Self; DalCor Pharma UK Inc. Advisory Panel; Self; Sirtex, Actelion Pharmaceuticals US, Inc.. Other Relationship; Self; Luitpold Pharmaceuticals Ltd., CSL Behring, Sanofi-Aventis. G.G. Schwartz: Research Support; Self; Roche Pharma, Sanofi, Resverlogix Corp. P.G. Steg: Consultant; Self; Amarin Corporation, AstraZeneca. Research Support; Self; Bayer AG. Consultant; Self; Bayer AG, Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company. Advisory Panel; Self; Novartis AG. Consultant; Self; Pfizer Inc., Sanofi. Research Support; Self; Sanofi, Servier. Consultant; Self; Novo Nordisk A/S, Regeneron Pharmaceuticals, Inc..

Type of Medium: Online Resource

ISSN: 0012-1797 , 1939-327X

URL: Article

DOI: 10.2337/db18-6-LB

Language: English

Publisher: American Diabetes Association

Publication Date: 2018

detail.hit.zdb_id: 1501252-9