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

Cardiovasc Diabetol. 2020 Feb 8;19(1):14. doi: 10.1186/s12933-020-0991-1.


Background: Mixed dyslipidemia [elevated non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides (TGs), and decreased HDL-C] is common in type 2 diabetes mellitus (T2DM) and is associated with increased cardiovascular risk. Non-HDL-C and apolipoprotein B (ApoB) are the preferred therapeutic targets for mixed dyslipidemia. Alirocumab is a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) that effectively reduces low-density lipoprotein cholesterol (LDL-C), non-HDL-C, ApoB, and lipoprotein(a) (Lp[a]), and is well-tolerated in individuals with T2DM.

Methods: The previously reported open-label ODYSSEY DM-DYSLIPIDEMIA trial data demonstrated the effects of alirocumab on individuals with non-HDL-C ≥ 100 mg/dL and TGs ≥ 150 and < 500 mg/dL receiving stable maximally tolerated statin (n = 413). This post hoc subgroup analysis of the primary trial investigated the effects of alirocumab [75 mg every 2 weeks (Q2W) with possible increase to 150 mg Q2W at Week 12] versus usual care [ezetimibe, fenofibrate, or no additional lipid-lowering therapy (LLT)] on non-HDL-C and other lipids in individuals with T2DM and baseline TGs ≥ 200 mg/dL and HDL-C < 40 mg/dL (men) or < 50 mg/dL (women).

Results: Alirocumab significantly reduced non-HDL-C [LS mean difference (standard error (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) [LS mean difference (SE), - 29.9% (5.4)] versus usual care from baseline to Week 24 (all P < 0.0001). Results were similar for alirocumab versus usual care. TG reductions were similar between alirocumab and usual care (no significant difference), but greater with fenofibrate versus alirocumab (P = 0.3371). Overall, alirocumab significantly increased HDL-C versus usual care [LS mean difference (SE), 7.9% (3.6); P < 0.05], although differences with alirocumab versus ezetimibe or fenofibrate were non-significant. Most individuals receiving alirocumab achieved ApoB < 80 mg/dL (67.9%) and non-HDL-C < 100 mg/dL (60.9%). Adverse event frequency was similar between alirocumab (67.2%) and usual care (70.7%). Additionally, no clinically relevant effect of alirocumab on change in glycemic parameters or use of antihyperglycemic agents was observed.

Conclusions: Alirocumab is an effective therapeutic option for individuals with T2DM, TGs ≥ 200 mg/dL, and HDL-C < 40 mg/dL (men) or < 50 mg/dL (women). Atherogenic lipid (ApoB and non-HDL) reductions were greater with alirocumab than ezetimibe, fenofibrate, or no LLT. Consistent with previous studies, alirocumab was generally well tolerated. Trial registration Clinicaltrials.gov, NCT02642159. Registered December 24, 2015, https://clinicaltrials.gov/ct2/show/NCT02642159.

Keywords: Alirocumab; DM-DYSLIPIDEMIA; Diabetes mellitus; HDL-C; Non-HDL-C; ODYSSEY; PCSK9; Triglycerides; Type 2 diabetes; Usual care.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Anticholesteremic Agents / adverse effects
  • Anticholesteremic Agents / therapeutic use*
  • Biomarkers / blood
  • Cholesterol, HDL / blood*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dyslipidemias / blood
  • Dyslipidemias / diagnosis
  • Dyslipidemias / drug therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • PCSK9 Inhibitors*
  • Protease Inhibitors / adverse effects
  • Protease Inhibitors / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Triglycerides / blood*


  • Antibodies, Monoclonal, Humanized
  • Anticholesteremic Agents
  • Biomarkers
  • Cholesterol, HDL
  • PCSK9 Inhibitors
  • Protease Inhibitors
  • Triglycerides
  • PCSK9 protein, human
  • alirocumab

Associated data

  • ClinicalTrials.gov/NCT02642159