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/m2) 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.

Maximizing retention in long‐term clinical trials of a weight loss agent: use of a dietitian support team

“…This retention programme was implemented proactively and was successful at improving upon the reported 53% 1‐year retention rate in the Rio‐North American study, which studied a similar weight loss drug in patients with similar BMI but without diabetes in the USA and Canada, also over a 1‐year time period 1, 19, and even improved upon the retention rate of Phase 3 trials conducted with more recently approved weight loss agents 2, 3, 4, 5.…”

“…On average, one‐third to one‐half of participants drops out of these large trials by 1 year 1, 2, 3, 4, 5. Such high‐attrition rates result in missing data that limit the interpretation and generalizability of findings 6.…”

Modern Obesity Pharmacotherapy: Weighing Cardiovascular Risk and Benefit

“…In the Controlled-Release Phentermine/Topiramate in Severely Obese Adults (EQUIP) trial, patients with BMI >35 but no weight-related comorbidities were provided with an office-based lifestyle intervention and randomized to high-dose, low-dose, and placebo groups. 29 Patients in the high-dose and low-dose treatment groups lost 10.9% and 5.1% of body weight at 1 year, respectively, whereas those receiving placebo lost 1.6% of body weight. Sixtyseven percent, 45%, and 17% of patients lost ≥5% of body weight in the high-dose, low-dose, and placebo groups, respectively.…”

“…Sixtyseven percent, 45%, and 17% of patients lost ≥5% of body weight in the high-dose, low-dose, and placebo groups, respectively. 29 The study population in the Effects of LowDose, Controlled-Release, Phentermine Plus Topiramate Combination on Weight and Associated Comorbidities in Overweight and Obese Adults (CONQUER) trial included patients with lower BMI (minimum 27) but ≥22 obesityrelated comorbidities. 30 Weight loss at 1 year was similar; 7.8% of body weight with an intermediate dosage of 7 mg phentermine plus 46 mg topiramate and 9.8% of body weight with the high-dose formulation, compared with 1.2% of body weight in the placebo group.…”

“…31 In both the EQUIP and CONQUER populations, high-dose treatment (and in some cases lower doses) improved SBP and diastolic blood pressure (DBP), LDL-C and HDL-C levels, and fasting serum glucose relative to placebo. 29,30 At 2-year follow-up of SEQUEL, phentermine plus topiramate reduced HbA 1c in patients with DM at baseline and reduced -34 In BLOOM, patients who continued therapy for a second year maintained most of their weight loss, but those who switched to placebo at 1 year regressed to the weight of the original placebo group. 34 In BLOOM, patients receiving lorcaserin had lower SBP and DBP, pulse rate, LDL-C and total cholesterol levels, insulin resistance, and C-reactive protein levels than those receiving placebo.…”