Level 2: Mid-level evidence

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 (BMI 27-45).

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Patients were randomized to one of two 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 two weight-related comorbidities (hypertension, dyslipidemia, diabetes or prediabetes or abdominal obesity).

Outcome data were available for 69% of the patients at one 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). Significantly more patients in each combination group had weight loss of at least 5% compared with placebo (70% for high dose, 62% for low-dose, 21% for placebo; P <0.0001), with an NNT of three for each dose.

The drug combination was associated with greater rates of dry mouth, paresthesia, constipation, dizziness, and dysgeusia (Lancet. 2011;377:1341-1352). 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;12:876-882).