PCSK9 inhibitor reduces atherogenic lipids in T2DM patients with mixed dyslipidemia

Effect of alirocumab on individuals with type 2 diabetes, high triglycerides, and low high‑density lipoprotein cholesterol

Literature - Colhoun HM, Leiter LA, Müller-Wieland D, et al. - Cardiovasc Diabetol 2020. doi: 10.1186/s12933-020-0991-1

Introduction and methods

Mixed dyslipidemia, i.e. elevated plasma triglycerides (TGs), TG-rich lipoprotein (TRL) and TRL cholesterol (TRL-c) levels and decreased levels of high-density lipoprotein cholesterol (HDL-c), is common in T2DM and contributes to risk of atherosclerotic CVD (ASCVD) [1–3]. Individuals with mixed dyslipidemia may have an elevated number of small, dense LDL particles [1, 8], as reflected by higher levels of ApoB, but not necessarily elevated LDL-c [7]. When LDL-c and ApoB are discordant, non-HDL-c and ApoB are considered to be stronger predictors of CVD risk than LDL-c [1, 9, 10].

The phase 3, randomized, open-label, parallel group, multinational ODYSSEY DM-DYSLIPIDEMIA trial examined treatment for 24 weeks with alirocumab, a PCSK9 inhibitor compared to usual treatment with ezetimibe, fenofibrate, omega-3, niacin, and no additional lipid-lowering therapy (LLT), in adults with T2DM and mixed dyslipidemia (non‐HDL-c ≥100 mg/dL and TGs ≥150 and <500 mg/dL) receiving stable maximally tolerated statin dose [4-5]. The trial showed that the primary endpoint of reduction in non-HDL-c with alirocumab was superior to usual care overall (mean difference of − 32.5% vs usual care at week 24; P<0.0001) [5]. The present study was a post hoc analysis that included 186 individuals taken from a total of 413 individuals participating in the ODYSSEY DM-DYSLIPIDEMIA trial. The 186 individuals investigated in the present study (randomized to alirocumab (n=128) or usual care (n=58)) had higher CVD risk, with non-HDL-c ≥100 mg/dL, TGs ≥200 mg/dL and HDL-c<40 mg/dL (men) or <50 mg/dL (women), as compared to the primary trial population. The aim of the present study was to focus on this higher risk subpopulation regarding efficacy of alirocumab treatment, and to provide additional analyses of other lipids. Primary endpoint in this study was percentage change from baseline in LDL-c, non-HDL-c, ApoB, LDL particle number, Lp(a), TGs, TRL-c, and HDL-c with alirocumab and usual care at week 24.

Main results

  • Alirocumab significantly reduced non-HDL-c (least squares [LS] mean difference [SE]: − 35.0% [3.9]), ApoB (LS mean difference [SE]: − 34.7% [3.6]), LDL-c (LS mean difference [SE]: − 47.3% [5.2]), LDL particle number (LS mean difference [SE] − 40.8% [4.1]) and Lp(a) (adjusted mean [SE] − 29.9% [5.4]) from baseline to week 24 versus usual care (all P <0.0001).
  • Alirocumab reduced TGs to a greater extent than usual care overall (adjusted mean difference [SE]: − 5.0% [5.2] vs usual care).
  • Alirocumab significantly increased HDL-c compared with usual care (LS mean difference [SE]: 7.9% [3.6]; P < 0.05). The LS mean difference (SE) in TRL-c was significantly reduced with alirocumab versus usual care overall (− 9.9% [4.8]; P=0.0402).
  • 67.9% of alirocumab-treated individuals achieved ApoB<80 mg/dL, as compared with 41.5% of individuals in the usual care group. 60.9% of alirocumab-treated individuals achieved non-HDL-c <100 mg/dL as compared with 32.0% of individuals in the usual care group.


Alirocumab treatment, as compared to usual treatment, significantly reduced LDL-c, non-HDL-c, ApoB, Lp(a), and LDL particle number and significantly increased HDL-c in a subgroup of individuals with T2DM and mixed dyslipidemia with higher CV risk. In addition, number of patients that achieved greater reduction of ApoB and non-HDL-c was higher with alirocumab than with usual care.


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Find this article online at Cardiovascular Diabetology

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