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PII‐39
Author(s) -
Kothare P.,
Linnebjerg H.,
Skrivanek Z.,
Reddy S.,
Mace K.,
Penña A.,
Han J.,
Turik M.,
Fineman M.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.164
Subject(s) - exenatide , lovastatin , medicine , statin , placebo , concomitant , cmax , pharmacology , type 2 diabetes , pharmacokinetics , endocrinology , diabetes mellitus , cholesterol , alternative medicine , pathology
BACKGROUND/AIMS Exenatide, a novel therapy for type 2 diabetes, among other glucoregulatory actions, slows gastric emptying and may alter the rate of absorption of concomitant oral drugs. As statins are commonly used in patients with type 2 diabetes, the potential interaction between exenatide and statins was evaluated. METHODS [A] PK study: open‐label, fixed‐sequence study in 21 healthy subjects. Lovastatin PK was evaluated after a single dose of lovastatin (40 mg) administered alone and in combination with concomitant exenatide (10 μg BID). [B] Long‐term clinical trials: Data from statin users in three 30‐week, placebo‐controlled trials for exenatide were combined and stratified based on concomitant placebo (n=168) or exenatide (n=180) use. Lipid profiles and statin dosage were compared between the active and placebo arms. RESULTS [A] PK study: Exenatide decreased mean lovastatin C max and AUC 0‐∞ by 28% and 40% respectively and increased median t max by about 4 hours. [B] Long‐term trials: Changes for fasting HDL‐C, LDL‐C, total cholesterol, triglycerides and the subjects (6 total) that increased their statin dose were not significantly different between the exenatide and placebo groups (see table). CONCLUSIONS Despite changes in lovastatin PK observed in an acute study, long‐term exenatide treatment did not alter HDL‐C, LDL‐C, total cholesterol, or triglycerides or require increases in statin dose. These data indicate that no change in statin dose is required during use with exenatide.LS mean±SE change from baseline to week‐30 Placebo LS mean±SE change from baseline to week‐30 Exenatide LS mean±SE of difference between treatments (95% CI) p‐value for the differenceHDL‐C (mg/dL) 1.7 ± 0.6 1.1 ± 0.6 −0.6 ± 0.7(−2.1, 0.8) 0.4052LDL‐C (mg/dL) 3.1 ± 2.7 1.7 ± 2.6 −1.5 ± 3.4(−8.1, 5.2) 0.6668Cholesterol (mg/dL) 5.3 ± 3.0 1.4 ± 2.9 −3.9 ± 3.8(−11.3, 3.5) 0.3009Triglycerides (mg/dL) 5.3 ± 13.4 −23.6 ± 12.9 −29.0 ± 16.7(−61.9, 3.9) 0.084Patients who increased statin dosage (%) 2.4 1.1 ‐ 0.4347Clinical Pharmacology & Therapeutics (2005) 79 , P46–P46; doi: 10.1016/j.clpt.2005.12.164