Escape phenomenon with pravastatin during long-term treatment of patients with hyperlipidemia associated with diabetes mellitus

Abstract

The escape phenomenon is considered to be a type of drug resistance caused by an increase in drug metabolism or an induction of enzymes or functional proteins toward which the drug is targeted. In practice, however, little evidence supports the actual occurrence of the escape phenomenon; rather, deterioration of compliance may be a more plausible cause. To address this issue, we compared changes in serum lipids in two groups of patients with diabetes mellitus during long-term treatment of hyperlipidemia with pravastatin sodium, a soluble 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Sixteen male and female patients with non-insulin-dependent diabetes mellitus and hyperlipidemia were enrolled in this study. All 16 patients had maintained decreased serum total cholesterol (TC) levels of 15% or more (from 261.5 ± 5.6 mg/dL to 195.6 ± 2.1 mg/dL, mean ± SE) for 3 months or longer after beginning pravastatin therapy. Their serum TC levels had then increased by 10% or more from the reduced levels (from 195.6 ± 2.1 mg/dL to 231.6 ± 3.3 mg/dL, mean ± SE). At this point, patients were randomly separated into two groups—group A receiving reinforcement of drug compliance and diet therapy and group B receiving no reinforcement. Changes in serum lipids, plasma glucose, glycated hemoglobin A 1c (Hb A 1c), and body weight were studied. Serum TC levels decreased significantly (234.4 ± 4.3 mg/dL to 205.6 ± 4.3 mg/dL) in serum group A, but remained unchanged (228.4 ± 4.6 mg/dL to 230.1 ± 2.9 mg/dL) in group B. No significant changes were observed in the levels of plasma glucose, Hb A 1c, or body weight. Results of this study suggest that insufficient diet therapy and poor drug compliance, rather than the escape phenomenon, account for a re-increase in serum TC levels after an initial decrease in levels with pravastatin therapy