Neutral Effects of Pitavastatin 4 mg and Pravastatin 40 mg on Blood Glucose and HbA1c Levels over 12 Weeks: Prespecified Safety Analysis from INTREPID (HIV-infected patieNts and TREatment with PItavastatin vs pravastatin for Dyslipidemia), a Phase 4 Trial

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 723-739-Lipids: Therapeutics & Case Reports
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-725
Judith A. Aberg*1, Craig A. Sponseller2, Vladimir A. Kryzhanovski3, Cynthia E. Kartman3 and Melanie A. Thompson4
1New York University School of Medicine, New York, NY, 2Kowa Pharmaceuticals America, Inc., Montgomery, AL, 3Eli Lilly and Company, Indianapolis, IN, 4AIDS Research Consortium of Atlanta, Atlanta, GA
Background: Dyslipidemia and insulin-resistance are common in HIV-infected adults on antiretroviral therapy. Antiretroviral and statin drug-drug interactions (DDI) as well as risk of incident diabetes with statins have been a recent concern. Pitavastatin (PTA) has a reduced potential for CYP-mediated DDI. In adults without HIV infection, PTA 4 mg showed significantly greater reduction in LDL-C vs pravastatin (PRA) 40 mg with neutral effects on glucose metabolism in 12-week Phase 3 and 4 studies. Superior LDL-C reduction with PTA 4 mg vs PRA 40 mg was confirmed in the INTREPID trial in HIV-infected patients with dyslipidemia. Objective: To compare the effects of PTA 4 mg and PRA 40 mg on fasting serum glucose (FSG) and HbA1c over 12 weeks in HIV-infected adults with dyslipidemia. Methods: INTREPID was a 12-week, randomized, double-blind Phase 4 study of PTA 4 mg vs PRA 40 mg in HIV-infected adults with dyslipidemia: LDL-C 130-220 mg/dL and TG ≤400 mg/dL (NCT01301066). Patients with CHD or its risk equivalent (e.g., diabetes) were excluded. FSG and HbA1c data were prospectively collected. Only patients who took study drug and had both Baseline (BL) and Week 12 values for FSG or HbA1c were included in these analyses. Mean changes from BL to Week 12 were compared between treatments using ANCOVA, with percent change in FSG/HbA1c as the dependent variable, and treatment, site, and hepatitis B/C status (Y/N) as independent variables. Results: Demographics were similar in both groups (N=126 in each): mean age ~50 years, BMI ~28 kg/m2, male ~86%, Caucasian ~80%. BL values for PTA and PRA, respectively: FSG (93.9 mg/dL and 95.6 mg/dL), HbA1c (5.4% and 5.5%), LDL-C (155.1 mg/dL and 154.6 mg/dL), HDL-C (49.6 mg/dL and 49.1 mg/dL), and TG (174.2 mg/dL and 172.4 mg/dL). The within group change in FSG (BL to Week 12) was -0.1 mg/dL for PTA (n=109) and 0.6 mg/dL for PRA (n=112). The difference between groups was not significant (p =0.26). There was no change (0%) in HbA1c at Week 12 with either PTA (n=110) or PRA (n=113). A greater decrease in LDL-C over 12 weeks was noted with PTA 4 mg (-49.4 mg/dL) vs PRA 40 mg (-33.6 mg/dL), p<0.001, while increases in HDL-C (1.9 mg/dL vs 2.7 mg/dL) and decreases in TG (-20.8 mg/dL vs -15.4 mg/dL) were comparable between PTA and PRA. Conclusion: While PTA 4 mg was superior to PRA 40 mg in LDL-C reduction after 12 weeks of therapy in HIV-infected adults with dyslipidemia, neither statin had significant effects on FSG nor HbA1c levels.

Disclosure: JAA: Investigator, Kowa Research Institute, , Kowa Research Institute, , Jansen Pharmaceuticals, , Merck & Co., , ViiV Healthcare. CAS: Employee, Kowa Pharmaceuticals America, Inc.. VAK: Employee, Eli Lilly & Company, Employee, Eli Lilly & Company. CEK: Employee, Eli Lilly & Company, Employee, Eli Lilly & Company, Employee, Eli Lilly & Company. MAT: Investigator, Bristol-Myers Squibb, Investigator, Cepheid, Inc., Investigator, Gilead Sciences, Investigator, GeoVax, Inc., Investigator, Kowa Research Institute, Investigator, Janssen/Tibotec Therapeutics, , Janssen/Tibotec Therapeutics, Investigator, Merck & Co., Investigator, Tobira Therapeutics, Investigator, ViiV Healthcare, , ViiV Healthcare.

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Sources of Research Support: INTREPID ( NCT01301066) is a study supported by Kowa Research Institute, Inc., Morrisville, NC.