Abstract
BackgroundThe 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/designThe 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.DiscussionIn 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 registrationClinicalTrials.gov, NCT02940366. Registered on 19 October 2016.
Highlights
The diabetogenic action of statins remains a concern, in patients at high risk for diabetes receiving intensive statin therapy
Several meta-analyses have demonstrated that statin treatment is associated with a 10–12% increased risk of new-onset diabetes mellitus (NOD) [3, 4]
We aim to evaluate changes in adiponectin to provide insight into the relevant mechanisms leading to statin-induced diabetes
Summary
The diabetogenic action of statins remains a concern, in patients at high risk for diabetes receiving intensive statin therapy. 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. Several meta-analyses have demonstrated that statin treatment is associated with a 10–12% increased risk of new-onset diabetes mellitus (NOD) [3, 4] This risk is further increased in patients treated with intensive statin regimens [5] and in subjects with preexisting risk factors for NOD [6]. In this regard, the implications of statin-induced diabetes on the long-term outcomes are uncertain, statintreated patients at high risk of developing NOD should be monitored regularly for changes in plasma glucose or hemoglobin A1c [7], especially when the patients are on intensive statin treatment. There are no randomized clinical trials addressing this problem
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