The dose-related weight loss was also accompanied by improvements in cardiovascular disease risk factors….
In the published CONQUER study, Dr. Michael Davidson (University of Chicago, IL) and colleagues say the results suggest that "facilitating weight loss by augmenting lifestyle changes with pharmacotherapies may decrease the risk for cardiovascular disease in obese and overweight patients with comorbidities."
Qsymia, previously known as Qnexa, was approved by the US Food and Drug Administration in July 2012 after the Endocrinologic and Metabolic Drugs Advisory Committee voted 20 to 2 in favor of approving the obesity drug early last year. The combination tablet of phentermine and topiramate is indicated for adults with a body-mass index (BMI) of more than 30 or adults with a BMI higher than 27 and at least one weight-related comorbidity such as hypertension, type 2 diabetes, or dyslipidemia. During the FDA advisory-panel deliberations, concerns were raised by committee members about possible increases in heart rate with Qsymia, something that physicians should regularly monitor in patients treated with the drug.
CONQUER is a 56-week randomized, double-blind, placebo-controlled study which includes patients with a BMI ranging from 27 to 45 and weight-related comorbidities. Of the 2487 patients in the trial, 53.9% had dyslipidemia and 52.5% had hypertension at baseline. More than one-quarter of patients had dyslipidemia and hypertension. Individuals were treated with placebo, a low dose of Qsymia, or a high dose of Qsymia (phentermine 7.5 mg/topiramate 46 mg and phentermine 15 mg/topiramate 92 mg, respectively).
In the placebo, low-dose, and high-dose treatment arms, patients with dyslipidemia lost 2.1%, 8.5%, and 10.5% of their body weight. Among those with hypertension, individuals in the three treatment arms lost 1.9%, 8.1%, and 10.1% of body weight, respectively. In line with the overall results, there were greater reductions in systolic and diastolic blood pressure in those treated with Qsymia compared with placebo, with larger reductions observed among those who lost more weight. There were also weight-loss-related improvements in HDL cholesterol, triglyceride levels, and inflammatory biomarkers among those treated with Qsymia.
Regardless of the treatment arm, individuals with dyslipidemia who lost more than 5% of their baseline weight had a greater reduction in triglycerides and non-HDL-cholesterol levels than those who lost less than 5% of their weight. Individuals who lost less than 5% had a 5.8% reduction in non-HDL cholesterol and a 5.5% reduction in triglycerides compared with respective reductions of 9.4% and 14.5% for those who lost 5% to 10% of their body weight (p<0.05). Individuals who lost more than 15% of their body weight reduced their non-HDL cholesterol 14.8% and triglycerides 39.8% (p<0.05 vs. less than 5%).
For individuals with hypertension at baseline, weight loss of more than 5% translated into a reduction of systolic blood pressure of 11.8 mm Hg compared with a reduction of 7.5 mm Hg for those who lost less than 5%. Weight loss of 10% to 15% resulted in even greater improvement in cardiovascular risk factors, report the investigators.
"This subgroup analysis of participants who had dyslipidemia or hypertension at baseline supports and extends this previous finding, demonstrating that compared with placebo, [Qsymia] treatment leads to significant weight loss accompanied by significant improvements in cardiovascular risk factors, including blood-pressure, lipid, and inflammatory-biomarker levels, as well as reductions in medication use," report Dr. Davidson and colleagues.
The overall safety of Qsymia in this cohort was similar to the overall population. Approximately 4% of patients with dyslipidemia treated with the drug experienced a cardiac-related adverse event, most of which were classified as mild or moderate. Palpitations were reported in 2.9% and 2.1% of patients treated with low- and high-dose Qsymia, respectively. For those with hypertension, 2.6% experienced a cardiac-related adverse event, the most common of which were palpitations.
The July 2012 FDA approval was accompanied by a risk evaluation and mitigation strategy (REMS), including a medication guide advising patients about important safety information and specific requirements for prescriber training and pharmacy certification. As part of the approval, Vivus, the maker of Qsymia, is required to conduct a postmarketing cardiovascular-outcomes trial to assess the effect of the weight-loss drug on major adverse cardiac events.
Davidson MH, Tonstad S, Oparil S, et al. "Changes in Cardiovascular Risk Associated With Phentermine and Topiramate Extended-Release in Participants With Comorbidities and a Body Mass Index ≥ 27 kg/m2". American Journal of Cardiology 2013; DOI:10.1016/j.amjcard.2012.12.038. Available at: http://www.ajconline.org/home.