Article

Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): Arandomised, placebo-controlled, phase 3 trial

Obesity Clinical Trials Programme, Duke University Medical Center, Durham, NC 27710, USA.
The Lancet (Impact Factor: 45.22). 04/2011; 377(9774):1341-52. DOI: 10.1016/S0140-6736(11)60205-5
Source: PubMed

ABSTRACT Obesity is associated with a reduction in life expectancy and an increase in mortality from cardiovascular diseases, cancer, and other causes. We therefore assessed the efficacy and safety of two doses of phentermine plus topiramate controlled-release combination as an adjunct to diet and lifestyle modification for weight loss and metabolic risk reduction in individuals who were overweight and obese, with two or more risk factors.
In this 56-week phase 3 trial, we randomly assigned overweight or obese adults (aged 18-70 years), with a body-mass index of 27-45 kg/m(2) and two or more comorbidities (hypertension, dyslipidaemia, diabetes or prediabetes, or abdominal obesity) to placebo, once-daily phentermine 7·5 mg plus topiramate 46·0 mg, or once-daily phentermine 15·0 mg plus topiramate 92·0 mg in a 2:1:2 ratio in 93 centres in the USA. Drugs were administered orally. Patients were randomly assigned by use of a computer-generated algorithm that was implemented through an interactive voice response system, and were stratified by sex and diabetic status. Investigators, patients, and study sponsors were masked to treatment. Primary endpoints were the percentage change in bodyweight and the proportion of patients achieving at least 5% weight loss. Analysis was by intention to treat. This study is registered with Clinical Trials.gov, number NCT00553787.
Of 2487 patients, 994 were assigned to placebo, 498 to phentermine 7·5 mg plus topiramate 46·0 mg, and 995 to phentermine 15·0 mg plus topiramate 92·0 mg; 979, 488, and 981 patients, respectively, were analysed. At 56 weeks, change in bodyweight was -1·4 kg (least-squares mean -1·2%, 95% CI -1·8 to -0·7), -8·1 kg (-7·8%, -8·5 to -7·1; p<0·0001), and -10·2 kg (-9·8%, -10·4 to -9·3; p<0·0001) in the patients assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively. 204 (21%) patients achieved at least 5% weight loss with placebo, 303 (62%; odds ratio 6·3, 95% CI 4·9 to 8·0; p<0·0001) with phentermine 7·5 mg plus topiramate 46·0 mg, and 687 (70%; 9·0, 7·3 to 11·1; p<0·0001) with phentermine 15·0 mg plus topiramate 92·0 mg; for ≥10% weight loss, the corresponding numbers were 72 (7%), 182 (37%; 7·6, 5·6 to 10·2; p<0·0001), and 467 (48%; 11·7, 8·9 to 15·4; p<0·0001). The most common adverse events were dry mouth (24 [2%], 67 [13%], and 207 [21%] in the groups assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively), paraesthesia (20 [2%], 68 [14%], and 204 [21%], respectively), constipation (59 [6%], 75 [15%], and 173 [17%], respectively), insomnia (47 [5%], 29 [6%], and 102 [10%], respectively), dizziness (31 [3%], 36 [7%], 99 [10%], respectively), and dysgeusia (11 [1%], 37 [7%], and 103 [10%], respectively). 38 (4%) patients assigned to placebo, 19 (4%) to phentermine 7·5 mg plus topiramate 46·0 mg, and 73 (7%) to phentermine 15·0 mg plus topiramate 92·0 mg had depression-related adverse events; and 28 (3%), 24 (5%), and 77 (8%), respectively, had anxiety-related adverse events.
The combination of phentermine and topiramate, with office-based lifestyle interventions, might be a valuable treatment for obesity that can be provided by family doctors.
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    • "Subjects were randomized to placebo, once-daily phentermine 7.5 mg plus topiramate 46.0 mg, or once-daily phentermine 15.0 mg plus topiramate 92.0 mg in a 2:1:2 ratio in 93 centers in the USA. The combination of phentermine and topiramate, with office-based lifestyle interventions, was associated with a significant decrease in A1c (−0.4%) compared with the control group (−0.1%).172 These benefits were sustained in the double-blind 52-week extension study, where the annualized incidence rates for progression to T2DM among subjects without diabetes at baseline were 3.7%, 1.7%, and 0.9% in the placebo, 7.5/46 mg, and 15/92 mg treatment groups, respectively. "
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    Therapeutics and Clinical Risk Management 03/2014; 10:173-188. DOI:10.2147/TCRM.S39564 · 1.47 Impact Factor
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    • "In EQUIP and CONQUER, there were small increases in mean heart rate: EQUIP, –0.2, –0.3, and 1.2 bpm with placebo, 3.75/23, and 15/92, respectively (Allison et al., 2012); CONQUER, –0.1, 0.1, and 1.7 bpm with placebo, 7.5/46, and 15/92, respectively (Gadde et al., 2011; Garvey et al., 2012). However, mean BP was decreased with PHEN/ TPM ER treatment vs placebo and there were no adverse events reported that were associated with changes in heart rate (Allison et al., 2012; Gadde et al., 2011; Garvey et al., 2012). 3.4. "
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