HMG co-A reductase inhibitors, commonly called statins, are an effective treatment for dyslipidemia and atherosclerotic heart disease with proven mortality benefit. While the lipid-lowering effects of statins are well-known, other metabolic effects, including effects on glucose tolerance and ectopic fat distribution, are less completely understood. Recent studies have shown that some statins may increase the risk of diabetes. Further, research has suggested that statins may have some benefit in nonalcoholic fatty liver disease (NAFLD), a condition associated with obesity that includes increased fat in the liver (steatosis) and, in some cases, inflammation and hepatocellular damage (steatohepatitis). Pitavastatin, approved by the United States Food and Drug Administration (FDA) in 2009, is the most recent statin to enter the market. Unlike most statins, pitavastatin is not primarily metabolized through cytochrome P450 (CYP450), and thus has reduced potential for interactions with other medications that are metabolized by CYP450. Previous studies have suggested that pitavastatin may be neutral to glucose homeostasis and may improve hepatic lipid. Neither of these effects has been proven definitively, however, and the current proposal aims to characterize in detail the effects of pitavastatin on glucose homeostasis, hepatic steatosis, and steatohepatitis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
50
Massachusetts General Hospital
Boston, Massachusetts, United States
Insulin-stimulated Glucose Uptake
insulin-stimulated glucose uptake measured by euglycemic hyperinsulinemic clamp
Time frame: 6 months
Liver Fat
liver fat content as measured by 1H-magnetic resonance spectroscopy
Time frame: 6 months
Alanine Aminotransferase (ALT)
alanine aminotransferase at the 6 month timepoint
Time frame: 6 months
Aspartate Aminotransferase (AST)
aspartate aminotransferase at 6 month timepoint
Time frame: 6 months
Hepatic Insulin Sensitivity
hepatic insulin sensitivity assessed by glucose infusion rate corrected for fluctuations in serum glucose ("M") during low-dose insulin clamp
Time frame: 6 months
Hemoglobin A1c (HbA1c)
Time frame: 6 months
Quantitative Insulin Sensitivity Check Index (QUICKI)
quantitative insulin sensitivity check index (QUICKI) at 6 months. Measure = 1/((log(glucose in mg/dL) + log(insulin in uU/mL))
Time frame: 6 months
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