Addition of Controlled-Release Combination of Phentermine and Topiramate to Lifestyle Intervention May Increase Weight Loss in Overweight or Obese Adults

DynaMed Weekly Update - Volume 6, Issue 16

Phentermine was used for the medical management of weight loss in combination with fenfluramine or dexfenfluramine until side effects related to cardiac valvular disease and pulmonary hypertension were linked to the fenfluramine/dexfenfluramine component. Since then, phentermine has been used for weight loss either as monotherapy or in combination with other medications. The CONQUER trial evaluated the addition of a controlled-release combination of phentermine and topiramate to a lifestyle and diet intervention for weight loss and metabolic risk reduction in 2,487 patients who were overweight to morbidly obese (body mass index 27-45 kg/m2). Patients were randomized to 1 of 2 doses of the study drug (high dose: phentermine 15 mg plus topiramate 92 mg; low dose: phentermine 7.5 mg plus topiramate 46 mg) vs. placebo once daily for 56 weeks. All patients had at least 2 weight-related comorbidities (hypertension, dyslipidemia, diabetes or prediabetes or abdominal obesity). Outcome data were available for 69% of the patients at 1 year. Mean weight loss was 10.2 kg for the high-dose combination, 8.1 kg for the low-dose combination and 1.4 kg for placebo (p < 0.0001) (level 2 [mid-level] evidence). Significantly more patients in each combination group had weight loss of at least 5% compared to placebo (70% for high dose, 62% for low-dose, 21% for placebo, p < 0.0001), with a number needed to treat (NNT) of 3 for each dose. The drug combination was associated with greater rates of dry mouth, paraesthesia, constipation, dizziness and dysgeusia (Lancet 2011 Apr 16;377(9774):1341). The weight loss seen with the low dose phentermine combination was comparable to that found in a recent trial of controlled release phentermine as monotherapy (Diabetes Obes Metab. 2010 Oct;12(10):876).

For more information, see the Weight loss medications for obesity in adults topic in DynaMed.