Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM): study protocol for a randomized controlled trial

Jun-Bean Park, Ji-Hyun Jung, Yeonyee E Yoon, Hack-Lyong Kim, Seung-Pyo Lee, Hyung-Kwan Kim, Yong-Jin Kim, Goo-Yeong Cho, Dae-Won Sohn, Jun-Bean Park, Ji-Hyun Jung, Yeonyee E Yoon, Hack-Lyong Kim, Seung-Pyo Lee, Hyung-Kwan Kim, Yong-Jin Kim, Goo-Yeong Cho, Dae-Won Sohn

Abstract

Background: The diabetogenic action of statins remains a concern, particularly in patients at high risk for diabetes receiving intensive statin therapy. Despite the risk of diabetes with statin use being considered a potential class effect, recent studies have suggested that pitavastatin exerts neutral or favorable effects on diabetogenicity. However, no randomized trial has compared the long-term effects of pitavastatin with those of other statins on glycemic control in populations at high risk for diabetes. Hence, we aim to assess the long-term effects of pitavastatin in comparison with atorvastatin on glucose metabolism in patients with metabolic syndrome (MetS).

Methods/design: The Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM) trial is a prospective, randomized, open-label, active control clinical trial of patients with MetS. We plan to randomize 500 patients with MetS (1:1) to receive high-dose pitavastatin (4 mg) or atorvastatin (20 mg) daily for 24 months. The primary endpoint will be the change in hemoglobin A1c after statin treatment. Secondary endpoints will include the following: (1) changes in biochemical markers, including insulin, C-peptide, homeostasis model assessment of insulin resistance and insulin secretion, and adiponectin; (2) changes in imaging parameters, including carotid elasticity metrics and indices of cardiac function; and (3) the incidence of clinical events, including new-onset diabetes and cardiovascular disease.

Discussion: In this trial, we will explore whether pitavastatin 4 mg does not disturb glucose metabolism in patients with MetS. It will also provide mechanistic information on statin type-dependent diabetogenic effects and surrogate data regarding vascular and cardiac changes achieved by intensive statin therapy.

Trial registration: ClinicalTrials.gov, NCT02940366 . Registered on 19 October 2016.

Keywords: Adiponectin; Cardiac function; Carotid elasticity; Glucose metabolism; Metabolic syndrome; Statin.

Conflict of interest statement

Ethics approval and consent to participate

The protocol of this prospective study was approved by the institutional review board of Seoul National University Hospital (1406-027-584). This study will be conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization good clinical practice guidelines. All participants will need to sign a written informed consent form explaining the details of this study. This form also states that participation is voluntary and that the patients can withdraw from participation at any point without any adverse consequence or disadvantage.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study design of the Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM) trial
Fig. 2
Fig. 2
Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) figure
Fig. 3
Fig. 3
Simplified schematic diagram demonstrating the study hypothesis and associated analyses. We hypothesize that pitavastatin may have a more favorable influence on glucose metabolism than atorvastatin, potentially mediated by its unique adiponectin-increasing effect. The possible antidiabetic property of pitavastatin may contribute to improvements in vascular and cardiac functions in patients with metabolic syndrome, a high-risk group for developing new-onset diabetes mellitus. The Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM) trial is specifically designed to explore this hypothesis by measuring the change in hemoglobin A1c (primary endpoint); changes in biochemical markers, including adiponectin; and changes in imaging markers, including carotid elasticity metrics and left ventricular function parameters, after statin therapy (secondary endpoints). NOD New-onset diabetes mellitus, HbA1c Hemoglobin A1c, LV Left ventricle

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