Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP)

Abstract

A 56-week randomized controlled trial was conducted to evaluate safety and efficacy of a controlled-release combination of phentermine and topiramate (PHEN/TPM CR) for weight loss (WL) and metabolic improvements. Men and women with class II and III obesity (BMI ≥ 35 kg/m(2)) were randomized to placebo, PHEN/TPM CR 3.75/23 mg, or PHEN/TPM CR 15/92 mg, added to a reduced-energy diet. Primary end points were percent WL and proportions of patients achieving 5% WL. Secondary end points included waist circumference (WC), systolic and diastolic blood pressure (BP), fasting glucose, and lipid measures. In the primary analysis (randomized patients with at least one postbaseline weight measurement who took at least one dose of assigned drug or placebo), patients in the placebo, 3.75/23, and 15/92 groups lost 1.6%, 5.1%, and 10.9% of baseline body weight (BW), respectively, at 56 weeks (P < 0.0001). In categorical analysis, 17.3% of placebo patients, 44.9% of 3.75/23 patients, and 66.7% of 15/92 patients, lost at least 5% of baseline BW at 56 weeks (P < 0.0001). The 15/92 group had significantly greater changes relative to placebo for WC, systolic and diastolic BP, fasting glucose, triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). The most common adverse events were paresthesia, dry mouth, constipation, dysgeusia, and insomnia. Dropout rate from the study was 47.1% for placebo patients, 39.0% for 3.75/23 patients, and 33.6% of 15/92 patients. PHEN/TPM CR demonstrated dose-dependent effects on weight and metabolic variables in the direction expected to be beneficial with no evidence of serious adverse events induced by treatment.

Figure 1

Patient disposition. After screening, all eligible patients underwent 56 weeks of treatment; 4-week blinded, postrandomization titration period, followed by 52 weeks at randomized dose. *Reason for discontinuation as reported while subject was receiving study drug; ^†Reason for study discontinuation. Subjects were able to discontinue study drug and study for different reason, however, reason was often the same. When they differed, the final reason for discontinuation from the study was used. D/C, discontinued; Meds, medications; PHEN/TPM CR, controlled-release phentermine/topiramate.

Figure 2

Plot of efficacy results with analysis A (prespecified ITT-LOCF). (a) Mean percent WL; (b) Patients achieving ≥5%, ≥10%, and ≥15% WL; (c) LS mean percent WL by baseline BMI category. Analysis A included data from patients who discontinued drug but remained in study and continued with data assessments through study completion even though no longer taking drug. The supplementary material presents mean percent WL for Analyses B and C. Error bars represent 95% confidence interval. ITT, intent-to-treat; LOCF, last observation carried forward; LS, least-squares; PHEN/TPM CR, controlled-release phentermine/topiramate; WL, weight loss.