Association between statin treatment and new-onset diabetes mellitus: a population based case–control study

Kim, Dong Won; Kim, Do Hoon; Park, Joo Hyun; Choi, Moon‐Young; Kim, Shinhye; Kim, Hyonchong; Seul, Da Eun; Park, Soo Gyeong; Jung, Jae-Hun; Han, Kyungdo; Park, Yong Gyu

doi:10.1186/s13098-019-0427-9

Cited by 10 publications

(8 citation statements)

References 43 publications

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“…The incidence of new-onset or worsening diabetes was lower in the bempedoic acid group than in the placebo group; overall, cases of new or worsening diabetes occurred in 4.0% of bempedoic acid-treated patients compared with 5.6% of placebo-treated patients (overall safety pool, nominal p < 0.05) [39]. By contrast, statins have been associated with an increased incidence of new-onset diabetes compared with placebo [50][51][52][53].…”

Section: Clinical Considerationsmentioning

confidence: 93%

Role of Bempedoic Acid in Clinical Practice

Ballantyne

Bays

Catapano

et al. 2021

Cardiovasc Drugs Ther

103

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Many patients do not achieve optimal low-density lipoprotein cholesterol (LDL-C) levels with statins alone; others are unable to tolerate statin therapy. Additional non-statin treatment options including ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, and bile acid sequestrants are often necessary to further reduce the risk of atherosclerotic cardiovascular disease. This review provides practical guidance as to the use of bempedoic acid to lower LDL-C and includes direction as to which patients may benefit and advice for safety monitoring during treatment. Bempedoic acid, a new class of agent, is a prodrug converted to bempedoyl-CoA by very long-chain acyl-CoA synthetase 1, an enzyme with high expression in the liver but that is undetectable in the skeletal muscle. Bempedoic acid inhibits the enzyme adenosine triphosphate (ATP)-citrate lyase, which lies two steps upstream from β-hydroxy β-methylglutaryl-CoA reductase in the cholesterol biosynthesis pathway. In clinical trials conducted in patients with or at risk for atherosclerotic cardiovascular disease or familial heterozygous hypercholesterolemia, bempedoic acid in combination with statins and/or ezetimibe significantly reduced LDL-C, apolipoprotein B, and high-sensitivity C-reactive protein compared with placebo. Bempedoic acid is generally well tolerated with no clinically meaningful increase in muscle-related symptoms relative to placebo, even in patients taking maximally tolerated statins. A small increase in serum uric acid (mean increase 0.8 mg/dL) is the most noteworthy adverse effect. Bempedoic acid provides an effective and generally well-tolerated medication to further reduce LDL-C in patients taking maximally tolerated statins or manage LDL-C levels in those who are unable to take statins. The potential for a reduced incidence of major cardiovascular events with bempedoic acid is being investigated in the CLEAR Outcomes trial, with results expected in 2023.

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Section: Clinical Considerationsmentioning

confidence: 93%

Role of Bempedoic Acid in Clinical Practice

Ballantyne

Bays

Catapano

et al. 2021

Cardiovasc Drugs Ther

103

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“…With common and long-term use of such medications, a number of adverse effects have been reported. Specifically, statins have been associated with liver damage (Aguirre et al, 2013), muscle discomfort (Pirillo and Catapano, 2015) and diabetes (Kim D. W. et al, 2019;Kim Y. S. et al, 2019). Yet, how the medication contributes to diabetes risk and impaired glucose metabolism is not clear.…”

Section: Introductionmentioning

confidence: 99%

Statin Use Associates With Risk of Type 2 Diabetes via Epigenetic Patterns at ABCG1

Liu¹,

Shen²,

Guo³

et al. 2020

Front. Genet.

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Statin is the medication most widely prescribed to reduce plasma cholesterol levels. Yet, how the medication contributes to diabetes risk and impaired glucose metabolism is not clear. This study aims to examine the epigenetic mechanisms of ABCG1 through which statin use associates with risk of type 2 diabetes. We determined the association between the statin use, DNA methylation at ABCG1 and type 2 diabetes/glycemic traits in the Framingham Heart Study Offspring (FHS, n = 2741), with validation in the Women's Health Initiative Study (WHI, n = 2020). The causal effect of statin use on the risk of type 2 diabetes was examined using a two-step Mendelian randomization approach. Next, based on transcriptome analysis, we determined the links between the medicationassociated epigenetic status of ABCG1 and biological pathways on the pathogenesis of type 2 diabetes. Our results showed that DNA methylation levels at cg06500161 of ABCG1 were positively associated with the use of statin, type 2 diabetes and related traits (fasting glucose and insulin) in FHS and WHI. Two-step Mendelian randomization suggested a causal effect of statin use on type 2 diabetes and related traits through epigenetic mechanisms, specifically, DNA methylation at cg06500161. Our results highlighted that gene expression of ABCG1, ABCA1 and ACSL3, involved in both cholesterol metabolism and glycemic pathways, was inversely associated with statin use, CpG methylation, and diabetic signatures. We concluded that DNA methylation site cg06500161 at ABCG1 is a mediator of the association between statins and risk of type 2 diabetes.

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“…The potential impact of statins in reducing diabetes mellitus (DM) has also been evaluated. According to the observations, long-term or first-time use of statins was not associated with DM incidence [70]. Nonetheless, a recent study on short-term consumption of statins (in comparison to those that have never used statins) showed that it might promote susceptibility to the development of DM [71].…”

Section: Statinsmentioning

confidence: 99%

Implications on the Therapeutic Potential of Statins via Modulation of Autophagy

Gorabi

Kiaie

Aslani

et al. 2021

Oxidative Medicine and Cellular Longevity

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Statins, which are functionally known as 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) inhibitors, are lipid-lowering compounds widely prescribed in patients with cardiovascular diseases (CVD). Several biological and therapeutic functions have been attributed to statins, including neuroprotection, antioxidation, anti-inflammation, and anticancer effects. Pharmacological characteristics of statins have been attributed to their involvement in the modulation of several cellular signaling pathways. Over the past few years, the therapeutic role of statins has partially been attributed to the induction of autophagy, which is critical in maintaining cellular homeostasis and accounts for the removal of unfavorable cells or specific organelles within cells. Dysregulated mechanisms of the autophagy pathway have been attributed to the etiopathogenesis of various disorders, including neurodegenerative disorders, malignancies, infections, and even aging. Autophagy functions as a double-edged sword during tumor metastasis. On the one hand, it plays a role in inhibiting metastasis through restricting necrosis of tumor cells, suppressing the infiltration of the inflammatory cell to the tumor niche, and generating the release of mediators that induce potent immune responses against tumor cells. On the other hand, autophagy has also been associated with promoting tumor metastasis. Several anticancer medications which are aimed at inducing autophagy in the tumor cells are related to statins. This review article discusses the implications of statins in the induction of autophagy and, hence, the treatment of various disorders.

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Association between statin treatment and new-onset diabetes mellitus: a population based case–control study

Cited by 10 publications

References 43 publications

Role of Bempedoic Acid in Clinical Practice

Role of Bempedoic Acid in Clinical Practice

Statin Use Associates With Risk of Type 2 Diabetes via Epigenetic Patterns at ABCG1

Implications on the Therapeutic Potential of Statins via Modulation of Autophagy

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