Effect of pitavastatin on glucose, HbA1c and incident diabetes: A meta-analysis of randomized controlled clinical trials in individuals without diabetes

Vallejo‐Vaz, Antonio J.; Seshasai, Sreenivasa Rao Kondapally; Kurogi, Kazumasa; Michishita, Ichiro; Nozue, Tsuyoshi; Sugiyama, Seigo; Tsimikas, Sotirios; Yoshida, Hiroshi; Ray, Kausik K.

doi:10.1016/j.atherosclerosis.2015.06.001

Cited by 95 publications

(60 citation statements)

References 49 publications

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“…There is a small but significant difference between the consensus percentages concerning the choice of pitavastatin in pre-diabetic patients when primary care physicians (91.8% consensus) are compared to other specialists (90.7% consensus). This is consistent with the recent publication of the first meta-analysis focusing on the individualised effects of pitavastatin [30], which has revealed that, relative to the controls (placebo and other statins), in subjects without prior diabetes the incidence of diabetes or deterioration of glucose metabolic control (fasting plasma glucose and/or HbA1c) is not increased. This evidence is in line with data collected in patients with impaired glucose tolerance, in these patients, pitavastatin showed a neutral effect and even some protection to the onset of diabetes [31, 32].…”

Section: Discussionsupporting

confidence: 90%

Consensus on the Statin of Choice in Patients with Impaired Glucose Metabolism: Results of the DIANA Study

Núñez-Cortés

Amenós

Gimilio

et al. 2016

Am J Cardiovasc Drugs

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Introduction and ObjectivesDespite the recognized clinical benefit of statins on cardiovascular prevention, providing correct management of hypercholesterolaemia, possible adverse effects of their use cannot be disregarded. Previously published data shows that there is a risk of developing diabetes mellitus or experiencing changes in glucose metabolism in statin-treated patients. The possible determining factors are the drug characteristics (potency, dose), patient characteristics (kidney function, age, cardiovascular risk and polypharmacy because of multiple disorders) and the pre-diabetic state.MethodsIn order to ascertain the opinion of the experts (primary care physicians and other specialists with experience in the management of this type of patient) we conducted a Delphi study to evaluate the consensus rate on diverse aspects related to the diabetogenicity of different statins, and the factors that influence their choice.ResultsConsensus was highly significant concerning aspects such as the varying diabetogenicity profiles of different statins, as some of them do not significantly worsen glucose metabolism. There was an almost unanimous consensus that pitavastatin is the safest statin in this regard.ConclusionsFactors to consider in the choice of a statin regarding its diabetogenicity are the dose and patient-related factors: age, cardiovascular risk, diabetes risk and baseline metabolic parameters (which must be monitored during the treatment), as well as kidney function.

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Section: Discussionsupporting

confidence: 90%

Consensus on the Statin of Choice in Patients with Impaired Glucose Metabolism: Results of the DIANA Study

Núñez-Cortés

Amenós

Gimilio

et al. 2016

Am J Cardiovasc Drugs

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“…73 Meta-analysis of the largest contemporary dataset involving 4,815 participants that assessed the impact of pitavastatin on glycemia and the risk of diabetes found that pitavastatin did not adversely affect glucose metabolism or the development of diabetes in comparison with placebo. 74 This was also determined in a recent network analysis that found pitavastatin to be the least diabetogenic. This analysis 2 36%, p=0.002), the OR of pitavastatin was the lowest (OR 0.74, 95% CI 0.31-1.77); whereas the highest risk was associated with atorvastatin 80 mg (OR 1.34, 95%CI 1.14-1.57).…”

Section: Review Diabetesmentioning

confidence: 99%

“…73 Unlike other statin drugs, pitavastatin has been demonstrated to consistently produce significantly greater HDL-C elevations that are maintained, or increased, over time. 41,[74][75][76][77] 79 Furthermore, in that study plasma EL concentrations in human subjects were found to be negatively associated with plasma HDL-C levels in patients with cardiovascular diseases, and pitavastatin treatment reduced plasma EL levels and increased HDL-C levels in patients with hypercholesterolaemia. 79 Whether other statins have this capacity to concomitantly increase key components of the reverse cholesterol transport pathway to ameliorate cellular cholesterol toxicity is unknown, yet perhaps this explains the unique relationship between pitavastatin and glucose.…”

Section: Review Diabetesmentioning

confidence: 99%

New Aspects of Cellular Cholesterol Regulation on Blood Glucose Control—Review and Perspective on the Impact of Statin Medications on Metabolic Health

Grice

Elmendorf

2017

US Endocrinology

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Cholesterol is an essential component of cell membranes, and during the past several years, diabetes researchers have found that membrane cholesterol levels in adipocytes, skeletal muscle fibers and pancreatic beta cells influence insulin action and insulin secretion. Consequently, it is thought that dysregulated cell cholesterol homeostasis could represent a determinant of type 2 diabetes (T2D). Recent clinical findings compellingly add to this notion by finding increased T2D susceptibility in individuals with alterations in a variety of cholesterol metabolism genes. While it remains imperfectly understood how statins influence glucose metabolism, the fact that they display an influence on blood glucose levels and diabetes susceptibility seems to intensify the emerging importance of understanding cellular cholesterol in glucose metabolism. Taking this into account, this review first presents cell system and animal model findings that demonstrate the negative impact of cellular cholesterol accumulation or diminution on insulin action and insulin secretion. With this framework, a description of how changes in cholesterol metabolism genes are associated with T2D susceptibility will be presented. In addition, the connection between statins and T2D risk will be reviewed with expanded information on pitavastatin, a newer statin medication that displays actions favoring metabolic health.

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“…The risk of new-onset diabetes is relatively circumscribed to patients who already have one or more risk factors for developing this disease [24,25] and seems to be higher with intensive statin therapy than with moderate-dose therapy [26]. Although some drugs may be more harmful than others [27,28], the current evidence is insufficient to recommend specific statins based on their diabetogenic potential [29,30]. Although the benefits of statin therapy seem to largely outweigh the risk of inducing diabetes, concern remains that some individuals might experience this side effect without deriving any benefit (i.e., individuals who would not experience a cardiovascular event even if left untreated).…”

Section: Side Effects Of Statinsmentioning

confidence: 99%

Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia

Ferreira

Silva

2016

Am J Cardiovasc Drugs

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Statin-ezetimibe combinations are a potentially advantageous therapeutic option for high-risk patients who need additional lowering of low-density lipoprotein cholesterol (LDL-C). These combinations may overcome some of the limitations of statin monotherapy by blocking both sources of cholesterol. Recently, a fixed-dose combination with atorvastatin, one of the most extensively studied statins, was approved and launched in several countries, including the USA. Depending on atorvastatin dose, this combination provides LDL-C reductions of 50-60%, triglyceride reductions of 30-40%, and highdensity lipoprotein cholesterol (HDL-C) increases of 5-9%. Studies comparing the lipid-lowering efficacy of the atorvastatin-ezetimibe combination with the alternatives of statin dose titration or switching to a more potent statin consistently showed that combination therapy provided greater LDL-C reduction, translating into a greater proportion of patients achieving lipid goals. Simvastatinezetimibe combinations have been shown to reduce the incidence of major atherosclerotic events in several clinical settings to a magnitude that seems similar to that observed with statins for the same degree of absolute LDL-C lowering. The atorvastatin-ezetimibe combination has also been shown to induce the regression of coronary atherosclerosis measured by intravascular ultrasound in a significantly greater proportion of patients than atorvastatin alone. Atorvastatin-ezetimibe combinations are generally well tolerated. Previous concerns of a possible increase in the incidence of cancer with ezetimibe were dismissed in large trials with long follow-up periods. In this paper, we examine the rationale for an atorvastatin-ezetimibe combination, review the evidence supporting it, and discuss its potential role in the management of dyslipidemia. Key PointsStatin-ezetimibe combinations are a realistic treatment option for patients who do not achieve low-density lipoprotein cholesterol (LDL-C) targets while receiving statin monotherapy and for patients prone to dose-dependent statin side effects.The IMPROVE-IT trial was the first to demonstrate a reduction in cardiovascular events with ezetimibe.Recently, combination therapy with atorvastatin plus ezetimibe was also associated with greater coronary plaque regression than atorvastatin alone.

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Effect of pitavastatin on glucose, HbA1c and incident diabetes: A meta-analysis of randomized controlled clinical trials in individuals without diabetes

Cited by 95 publications

References 49 publications

Consensus on the Statin of Choice in Patients with Impaired Glucose Metabolism: Results of the DIANA Study

Consensus on the Statin of Choice in Patients with Impaired Glucose Metabolism: Results of the DIANA Study

New Aspects of Cellular Cholesterol Regulation on Blood Glucose Control—Review and Perspective on the Impact of Statin Medications on Metabolic Health

Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia

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