VIVUS, Inc. announced that results from a new study evaluating the cardiovascular safety of Qsymia (phentermine and topiramate extended-release) capsules CIV will be published in the February 1, 2019 issue of The Journal of Clinical Endocrinology & Metabolism. This retrospective study, conducted using medical claims databases, was prompted by the observation in clinical trials that participants taking Qsymia had higher heart rates than those taking placebo. The new findings indicate that the combined risk of major adverse cardiovascular events (MACE) was not elevated in patients currently taking Qsymia, or concurrently taking both phentermine and topiramate, compared with former users of these medications. The number of MACE events (3 events during 3,245 person-years of follow-up) was too few to draw a definitive conclusion from the data. More than 500,000 patients were included in this retrospective study, which evaluated risk of MACE among current users of Qsymia, phentermine and topiramate in combination (PHEN/TPM), phentermine (PHEN), and topiramate (TPM), compared to the risk among patients who were former users who had discontinued these medications MACE was defined as hospitalization for acute myocardial infarction (AMI) or stroke or in-hospital cardiovascular-related death, as determined via discharge status and ICD-9-CM diagnoses. The efficacy and safety of Qsymia have been demonstrated in multiple clinical trials and peer-reviewed publications, including: A Phase 3 randomized, placebo-controlled Phase 3 trial conducted in 1,267 obese adults with body-mass index (BMI) = 35 kg/m2 (EQUIP).2 Patients were randomized to placebo, phentermine/topiramate controlled release (PHEN/TPM CR) 3.75/23 mg, or PHEN/TPM CR 15/92 mg, added to a reduced-energy diet. At 56 weeks, patients lost 1.6%, 5.1% and 10.9%, respectively, of baseline body weight. A Phase 3 randomized, placebo-controlled 56-week trial conducted in 2,487 adults with BMI 27 "45 kg/m2 and two or more comorbidities (hypertension, dyslipidaemia, diabetes or prediabetes, or abdominal obesity) (CONQUER).3 Patients were randomly assigned to receive PHEN/TPM CR 7.5/46.0 mg (n = 498), PHEN/TPM CR 15.0/92.0 mg (n = 995) or placebo (n = 994). At 56 weeks, change in bodyweight in the 2,448 patients available for analysis was "1.4 kg, "8.1 kg, and "10.2 kg. A two-year Phase 3 randomized, placebo-controlled study (SEQUEL)4, which was a 52-week extension study of CONQUER. A total of 866 patients from CONQUER were eligible for the extension study, of which 676 elected to participate in SEQUEL. At week 108, PHEN/TPM CR was associated with significant, sustained weight loss(intent-to-treat with last observation carried forward; p < 0.0001 compared with placebo). Percentage changes from baseline in body weight were "1.8%,"9.3%, and "10.5% for placebo, 7.5/46, and 15/92, respectively. Significantly more PHEN/TPM CR "treated subjects at each dose achieved = 5%, = 10%, = 15%, and = 20% weight loss compared with placebo (p < 0.001). No cardiovascular safety signals were detected. A sub-analysis of SEQUEL conducted in 475 patients with prediabetes and/or metabolic syndrome (MetS). After 108 weeks, subjects with prediabetes and/or MetS in the placebo, 7.5/46, and 15/92 groups experienced mean percent weight loss of 2.5%, 10.9%, and 12.1%, respectively (p < 0.0001 vs. placebo). These losses were associated with reductions of 70.5% and 78.7% in the annualized incidence rate of type 2 diabetes for those receiving 7.5/46 and 15/92, respectively (p < 0.05), versus placebo. No cardiovascular safety signals were observed in this patient subset. A Phase 2 randomized, double-blind, placebo-controlled study of PHEN/TPM CR 15/92 for the treatment of moderate to severe obstructive sleep apnea (OSA) in obese adults.6 A total of 45 patients were randomized to placebo (n = 23) or PHEN/TPM CR (n = 22) for 28-week treatment periods in addition to lifestyle-modification counseling. At 28 weeks, changes in the apnea-hypopnea index (AHI), significantly favored PHEN/TPM CR over placebo (-31.5 events/h vs.16.6 events/h, p = 0.0084). At week 28 there was also a positive, significant (p = 0.0003) correlation between percent change in weight and change in AHI. Authors also noted significant improvements in overnight oxygen saturation and reduction in blood pressure compared to placebo. A subset analysis of health-related quality of life (HRQOL) conducted in 2,374 patients who had participated in EQUIP (n = 751) or CONQUER (n = 1,623) and completed HRQOL questionnaires at weeks 28 and 56. Significant improvements in both obesity-specific and physical HRQOL were observed at 56 weeks in both trials (p < 0.0001).Although reduction in BMI accounted for the majority of improvements obesity-specific and physical HRQOL, decrease in depressive symptoms was also a significant mediator.