NEW ORLEANS, LA— Treatment with a low-dose, controlled-release combination of phentermine and topiramate (PHEN/TPM CR) resulted in significant weight loss and improvements in cardiovascular risk factors in a comorbid population of overweight and obese subjects in two consecutive clinical trials (CONQUER and SEQUEL) reported on at ACC.11, the American College of Cardiology’s 60th Annual Scientific Session.
CONQUER, a Phase 3 double-blind, placebo-controlled 56-week trial was conducted with 2,487 overweight and obese subjects with two or more weight-related comorbidities; subjects were randomized 2:1:2 to treatment with placebo, PHEN/TPM CR 7.5/46mg, or PHEN/TPM CR 15/92mg and provided lifestyle intervention and treatment to standard of care. Eligible subjects at a subset of sites were enrolled in the 52-week SEQUEL trial for a second year of treatment maintaining randomization and blinding. The two consecutive trials covered a 108-week period.
Patients in the extension study SEQUEL (N=675) had comparable baseline demographics to the originally randomized population: age 51 years, 66,4% female, 85.3% Caucasian, body mass index 36kg/m2, blood pressure 128/80mmHg. At baseline, 51.1% were hypertensive and 34.5% were dyslipidemic. The least squares (LS) mean weight loss at 56 weeks was 1.2%, 7.8% and 9.8% for placebo, PHEN/TPM CR 7.5/46mg and PHEN/TPM CR 15/92mg, respectively; and at 108 weeks was 1.8%, 9.3%, and 10.5% (ITT-LOCF, P<0.0001).
Blood pressure decreased in hypertensive subjects over the 108 weeks in all three groups, -6.7 mmHg, -6.9 mmHg, and -8.6mmHg systolic, and -5.7mmHg, -4.8mmHg and -5.8mmHg diastolic, respectively, with placebo subjects requiring additional antihypertensive medications compared with PHEN/TPM CR-treated subjects. In dyslipidemic patients, HDL (9.1mg/dL, 11.4mg/dL and 16.7%; ITT-LOCF, PHEN/TPM CR 15/92mg P<0.015) and triglycerides (-14.3mg/dL, -25.9mg/dL and -26.3%; ITT-LOCF, P=0.055 and 0.015) showed improvement over the full treatment period. The most common adverse events were sinusitis, dry mouth, paresthesia, constipation and dysgeusia.
The study investigators, Michael Davidson, MD, FACC, FACP, FNLA, from the University of Chicago Pritzker School of Medicine, Chicago, and colleagues concluded that treatment with PHEN/TPM CR produced and maintained significant weight loss and improvements in CV risk factors in a comorbid population of overweight and obese subjects over 2 years, and led to a reduction in the number of concomitant medications.