Safety of Proprotein Convertase Subtilisin/Kexin Type 9 Monoclonal Antibodies in Regard to Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Chen, Qiwen; Wu, Guodong; Li, Chuang; Qin, Xueting; Li, Rui; Zhang, Mei

doi:10.1007/s40256-019-00386-w

Cited by 18 publications

(20 citation statements)

References 48 publications

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“…In the SPIRE 104 studies, although bococizumab use was not associated with significant increase in new-diabetes, the early termination of the trials precluded the ability to assess adverse effect on glycemic control. The results of three recent meta-analyses 1 , 79 , 126 are in line with the findings of the previous studies. However, one 126 of the aforementioned meta-analyses has elaborated that the imbalance in the background LLT of the control arms may have masked the effect of PCSK9 inhibitors on diabetes.…”

Section: Safety Of Pcsk9 Monoclonal Antibodiessupporting

confidence: 89%

“…The results of three recent meta-analyses 1 , 79 , 126 are in line with the findings of the previous studies. However, one 126 of the aforementioned meta-analyses has elaborated that the imbalance in the background LLT of the control arms may have masked the effect of PCSK9 inhibitors on diabetes.…”

Section: Safety Of Pcsk9 Monoclonal Antibodiessupporting

confidence: 89%

“…It has been hypothesized that the significant LDL-C-lowering effect of the PCSK9 inhibitors may negatively affect the glycemic status, namely the new-onset diabetes, as suggested with statin therapy to be associated with an increase in diabetes incidence 104,126 . It has been postulated that the genetic variations in the targets of statins and PCSK9 inhibitors i.e.…”

Section: Diabetesmentioning

confidence: 99%

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Efficacy and safety of PCSK9 monoclonal antibodies: an evidence-based review and update

Kaddoura

Orabi

Salam

2020

Journal of Drug Assessment

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Objective: Treatment of dyslipidemia lowers cardiovascular (CV) risk. Although statin use is a cornerstone therapy, many patients are not achieving their risk-specific low-density lipoprotein cholesterol (LDL-C) goals. The proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies have been extensively studied as lipid-lowering therapy (LLT). Herein, we present an updated evidencebased review of the efficacy and safety of PCSK9 monoclonal antibodies in the treatment of familial and non-familial hypercholesterolemia. Methods: PubMed database was searched to review Phase III studies on PCSK9 monoclonal antibodies. Then, the US National Institutes of Health Registry and the WHO International Clinical Trial Registry Platform were searched to identify and present the ongoing research. Results: PCSK9 monoclonal antibodies were investigated for the treatment of dyslipidemia, as a single therapeutic agent or as an add-on therapy to the traditional LLT. They proved effective and safe in the treatment of familial and non-familial hypercholesterolemia, and in the prevention of adverse CV events. Conclusions: The use of PCSK9 monoclonal antibodies in the treatment of dyslipidemia is currently recommended to achieve risk-specific LDL-C goal to reduce adverse CV events. Future results of the ongoing research might expand their clinical generalizability to broader patient populations.

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Section: Safety Of Pcsk9 Monoclonal Antibodiessupporting

confidence: 89%

Section: Safety Of Pcsk9 Monoclonal Antibodiessupporting

confidence: 89%

Section: Diabetesmentioning

confidence: 99%

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Efficacy and safety of PCSK9 monoclonal antibodies: an evidence-based review and update

Kaddoura

Orabi

Salam

2020

Journal of Drug Assessment

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“…12 Most studies investigating PCSK9i have stated that there is no significant risk of causing new-onset diabetes. [13][14][15][16] However, one review states that there is a risk of increased plasma glycemia. 17 Moreover, there are few metaanalyses regarding ezetimibe in conjunction with statins on whether it may cause incident diabetes.…”

Section: Introductionmentioning

confidence: 99%

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Ezetimibe on Risk of New-Onset Diabetes: A Systematic Review and Meta-Analysis of Large, Double-Blinded Randomized Controlled Trials

Chiu

Pratt

Feinn

et al. 2020

J Cardiovasc Pharmacol Ther

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Background: Previous meta-analyses have shown that statins may cause incident diabetes. This article reviews randomized controlled trials using proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) or ezetimibe on the risk of new-onset diabetes. Methods: Eight trials involving PCSK9i and 3 trials of ezetimibe were selected for review. PubMed, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov were thoroughly searched for relevant trials. Inclusion criteria included at least 100 patients per treatment arm, follow-up of at least 52 weeks, and at least double-blinded study design. Exclusion criteria included patients with previously diagnosed diabetes, nonrandomized, placebo-controlled, open-label, and crossover trials. The primary outcome was the number of incident diabetes cases. A random effects model was used. Heterogeneity in effect sizes was measured with I 2 parameter and the Q statistic was used to test for excessive between-study heterogeneity. Results: A total of 52 214 participants for the PCSK9i and a total of 20 084 for the ezetimibe meta-analyses were included. Participants randomized to PCSK9i did not differ from the control patients in diabetes incidence (risk ratio [RR] = 0.99, P = .87, 95% CI = 0.92-1.07). Participants randomized to ezetimibe did not differ from the control patients in diabetes incidence (RR = 1.05, P = .37, 95% CI = 0.95-1.15). Discussion: The use of PCSK9i and ezetimibe does not appear to impact the risk of incident diabetes mellitus when added to guideline-directed medical therapy.

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“…Findings from the published literature did not find a statistically significant difference in terms of neurocognitive adverse events with alirocumab and evolocumab use when compared with the control. [ 1 55 57 59 60 64 ] As previously suggested that a significant reduction in LDL-C levels with statin use may influence the glycemic status of the body and lead to an increase in diabetes incidence,[ 58 65 ] the current body of evidence[ 1 60 65 ] did not prove that alirocumab[ 33 55 59 66 ] nor evolocumab[ 48 57 67 68 69 70 ] use would significantly increase the incidence of new-onset diabetes or worsen the preexisting diabetic condition.…”

Section: Adverse Effectsmentioning

confidence: 99%

PCSK9 monoclonal antibodies: An overview

2020

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PCSK9 monoclonal antibodies are novel lipid-lowering therapy that have been extensively studied in patients with hypercholesterolemia either as monotherapy or as an add-on to other LLTs. PCSK9 monoclonal antibodies have significantly reduced the low-density lipoprotein cholesterol (LDL-C) plasma level resulting in a better LDL-C goal attainment. The commercially available PCSK9 monoclonal antibodies, alirocumab and evolocumab, have demonstrated reductions in major adverse cardiovascular events such as myocardial infarction, stroke, unstable angina, and the need for coronary revascularization but not mortality. PCSK9 monoclonal antibodies have demonstrated a favorable safety profile. The most reported side effects are mild injection site with no causal relationship proven between the inhibition of PCSK9 and neurocognitive or glycemic adverse events. In this overview, the efficacy and safety of PCSK9 monoclonal antibodies in the treatment of primary and familial hypercholesterolemia will be discussed.

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Safety of Proprotein Convertase Subtilisin/Kexin Type 9 Monoclonal Antibodies in Regard to Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Cited by 18 publications

References 48 publications

Efficacy and safety of PCSK9 monoclonal antibodies: an evidence-based review and update

Efficacy and safety of PCSK9 monoclonal antibodies: an evidence-based review and update

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Ezetimibe on Risk of New-Onset Diabetes: A Systematic Review and Meta-Analysis of Large, Double-Blinded Randomized Controlled Trials

PCSK9 monoclonal antibodies: An overview

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