Marja-Riitta Taskinen1, Stefano Del Prato2, Maja Bujas-Bobanovic3, Michael J Louie4, Alexia Letierce5, Desmond Thompson4, Helen M Colhoun6. 1. Cardiovascular Research Unit, Diabetes and Obesity Research Program, University of Helsinki, Helsinki, Finland. Electronic address: marja-riitta.taskinen@helsinki.fi. 2. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. 3. Sanofi, Paris, France. 4. Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA. 5. Sanofi, Chilly-Mazarin, France. 6. University of Edinburgh, Edinburgh, UK.
Abstract
BACKGROUND AND AIMS: Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, significantly reduces low-density lipoprotein cholesterol (LDL-C). We evaluated the efficacy and safety of alirocumab in individuals with type 2 diabetes mellitus (T2DM) with versus without mixed dyslipidaemia (MDL, defined as baseline LDL-C ≥70 mg/dL [1.8 mmol/L] and triglycerides ≥150 mg/dL [1.7 mmol/L]). METHODS: Data from 812 individuals with T2DM, from theplacebo-controlled, 78-week, Phase 3 ODYSSEY LONG TERM trial of alirocumab 150 mg every 2 weeks (Q2W), on a background of maximally tolerated statins ± other lipid-lowering therapies, were pooled according to MDL status. Efficacy endpoints included percentage change from baseline to Week 24 in calculated LDL-C and other lipids/lipoproteins. RESULTS: In individuals with T2DM who received alirocumab 150 mg Q2W, mean LDL-C changes from baseline to Week 24 were -62.6% (vs. -6.0% with placebo) in those with MDL and -56.1% (vs. 5.6%) in those without MDL, with no significant between-group difference (p-interaction = 0.0842). Risk-based LDL-C goals (<70 [1.8 mmol/L] or <100 mg/dL [2.6 mmol/L]) were achieved by 69.1% and 72.4% of alirocumab-treated individuals with and without MDL, respectively. Mean reductions in non-high-density lipoprotein cholesterol (49.2% and 47.8%) and apolipoprotein B (50.2% and 49.1%) with alirocumab were also similar in those with and without MDL, respectively. Treatment-emergent adverse event rates were comparable between alirocumab-treated individuals with T2DM, with and without MDL. CONCLUSIONS: Reductions in LDL-C and other lipids with alirocumab, as well as safety and tolerability, were comparable between individuals with T2DM and with versus without MDL.
RCT Entities:
BACKGROUND AND AIMS: Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, significantly reduces low-density lipoprotein cholesterol (LDL-C). We evaluated the efficacy and safety of alirocumab in individuals with type 2 diabetes mellitus (T2DM) with versus without mixed dyslipidaemia (MDL, defined as baseline LDL-C ≥70 mg/dL [1.8 mmol/L] and triglycerides ≥150 mg/dL [1.7 mmol/L]). METHODS: Data from 812 individuals with T2DM, from the placebo-controlled, 78-week, Phase 3 ODYSSEY LONG TERM trial of alirocumab 150 mg every 2 weeks (Q2W), on a background of maximally tolerated statins ± other lipid-lowering therapies, were pooled according to MDL status. Efficacy endpoints included percentage change from baseline to Week 24 in calculated LDL-C and other lipids/lipoproteins. RESULTS: In individuals with T2DM who received alirocumab 150 mg Q2W, mean LDL-C changes from baseline to Week 24 were -62.6% (vs. -6.0% with placebo) in those with MDL and -56.1% (vs. 5.6%) in those without MDL, with no significant between-group difference (p-interaction = 0.0842). Risk-based LDL-C goals (<70 [1.8 mmol/L] or <100 mg/dL [2.6 mmol/L]) were achieved by 69.1% and 72.4% of alirocumab-treated individuals with and without MDL, respectively. Mean reductions in non-high-density lipoprotein cholesterol (49.2% and 47.8%) and apolipoprotein B (50.2% and 49.1%) with alirocumab were also similar in those with and without MDL, respectively. Treatment-emergent adverse event rates were comparable between alirocumab-treated individuals with T2DM, with and without MDL. CONCLUSIONS: Reductions in LDL-C and other lipids with alirocumab, as well as safety and tolerability, were comparable between individuals with T2DM and with versus without MDL.
Authors: Alberto J Lorenzatti; Freddy G Eliaschewitz; Yundai Chen; Juming Lu; Alexis Baass; Maria Laura Monsalvo; Nan Wang; Andrew W Hamer; Junbo Ge Journal: Diabetes Obes Metab Date: 2019-04-02 Impact factor: 6.577
Authors: Dirk Müller-Wieland; Daniel J Rader; Patrick M Moriarty; Jean Bergeron; Gisle Langslet; Kausik K Ray; Garen Manvelian; Desmond Thompson; Maja Bujas-Bobanovic; Eli M Roth Journal: J Clin Endocrinol Metab Date: 2019-11-01 Impact factor: 5.958