CONQUER: Safety, Efficacy of Phentermine + Topiramate for Weight Reduction Among Overweight or Obese Individuals with Weight-Related Comorbidities

Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial.
Lancet. 2011;377:1341-1352. 

The CONQUER study was a randomized, double-blind, placebo-controlled study that evaluated the safety and efficacy of once-daily, controlled-release phentermine plus topiramate for weight reduction among those who were overweight or obese and had weight-related comorbidities.  

Subjects were aged 18-70 years and had BMI 27-45 kg/m2 (no lower BMI limit set for subjects with diabetes at baseline) and ≥2 of the following comorbidities  

  • Systolic BP 140-160 mm Hg (130-160 mm Hg in those with diabetes), diastolic BP 90-100 mm Hg (85-100 mm Hg in those with diabetes), or taking ≥2 antihypertensive agents  
  • TG 47.2-81.4 mg/dL or using ≥2 lipid-lowering agents  
  • FBG >100 mg/dL, blood glucose >140 mg/dL at 2 h after oral glucose load during OGTT, or diagnosed type 2 diabetes managed with lifestyle changes or metformin monotherapy  
  • Waist circumference ≥40 in men; ≥35 in women  

Subjects were randomized to one of the following over 56 weeks  

  • Once-daily, controlled-release phentermine 7.5 mg plus topiramate 46.0 mg* (n=488)  
  • Once-daily, controlled-release phentermine 15.0 mg plus topiramate 92.0 mg* (n=981)  
  • Placebo (n=979)  

All subjects received standardized counseling for diet and lifestyle modification. Participants were also stratified based on sex and diabetic status (diabetes only; not prediabetes). Study visits took place at screening, baseline, weeks 2 and 4 during titration, and every 4 weeks thereafter. Baseline characteristics were similar between groups.  

The study’s co-primary outcomes were mean percentage change in body weight and proportion of subjects achieving ≥5% weight loss. Secondary outcomes included weight loss, proportion of subjects achieving ≥10% weight loss, and change in waist circumference.  

Results:
Primary endpoints (intention-to-treat analysis with last observation carried forward):
 

First co-primary endpoint: change in body weight  

  • Once-daily, controlled-release phentermine 7.5 mg plus topiramate 46.0 mg* (n=488): -17.8 lb absolute change in body weight; least squares mean (LSM), -7.8% (95% CI, -8.5 to -7.1); P<0.0001 vs placebo  
  • Once-daily, controlled-release phentermine 15.0 mg plus topiramate 92.0 mg* (n=981): -22.4 lb absolute change in body weight; LSM, -9.8% (95% CI, -10.4 to -9.3); P<0.0001 vs placebo  
  • Placebo† (n=979): -1.4 lb absolute change in body weight; LSM, -1.2% (95% CI, -1.8 to -0.7) 

Second co-primary endpoint: proportion of subjects achieving ≥5% weight loss  

  • Once-daily, controlled-release phentermine 7.5 mg plus topiramate 46.0 mg* (n=488): 62% (n=303) (OR, 6.3 [95% CI, 4.9 to -8.0]); P<0.0001 vs placebo  
  • Once-daily, controlled-release phentermine 15.0 mg plus topiramate 92.0 mg*† (n=981): 70% (n=687) (OR, 9.0 [95% CI, 7.3 to 11.1]); P<0.0001 vs placebo  
  • Placebo (n=979): 21% (n=204)  

A similar pattern was noted for achievement of ≥10% weight loss:  

  • Once-daily, controlled-release phentermine 7.5 mg plus topiramate 46.0 mg* (n=488): 37%  
  • Once-daily, controlled-release phentermine 15.0 mg plus topiramate 92.0 mg*† (n=981): 48%  
  • Placebo (n=979): 7%  

Analysis of secondary outcomes showed that when compared with the placebo group, use of phentermine + topiramate resulted in:  

  • Greater weight loss when subgroups were analyzed by sex, age, race, baseline BMI, and comorbidities  
  • Greater number of subjects achieving ≥10% weight loss  
  • Significant improvements in waist circumference  

Dose-related trends were observed for rates of dry mouth, constipation, dysgeusia, paresthesia, insomnia, dizziness, anxiety, irritability, and disturbance in attention. Depression- and anxiety-related adverse events, respectively, were seen as follows:  

  • Phentermine 7.5 mg plus topiramate 46.0 mg: 4% (19); 5% (24)  
  • Phentermine 15.0 mg plus topiramate 92.0 mg: 7% (73); 8% (77)  
  • Placebo: 4% (38); 3% (28)  

The rate of serious adverse events was similar across groups:  

  • Phentermine 7.5 mg plus topiramate 46.0 mg: 3% (n=15)  
  • Phentermine 15.0 mg plus topiramate 92.0 mg: 5% (n=50)  
  • Placebo: 4% (n=40)  

*All subjects had dose titration during the initial 4 weeks of the study to achieve the assigned study doses, which were maintained for the remaining 52 weeks of the study  

Enrollment skewed to improve capture of risk-benefit profile; higher dose of phentermine + topiramate also believed to be more effective  

 

August 2012  

 This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest. 

Related content: 

Overview: SEQUEL: Longer-Term Safety, Efficacy of Phentermine + Topiramate for Weight Reduction Among Overweight or Obese Individuals with Cardiometabolic Disease  

CONQUER: Design  

CONQUER: Randomization and Endpoints  

CONQUER: Subject Profile  

CONQUER Co-Primary Outcome: Change in Body Weight*  

CONQUER Co-Primary Outcome: Proportion of Subjects Achieving ≥5% Weight Loss*  

CONQUER: Secondary Outcomes and Adverse Events  

SEQUEL: Design Extension of CONQUER Study  

SEQUEL: Primary and Secondary Outcomes  

SEQUEL Co-Primary Outcome: Change in Body Weight*  

SEQUEL Co-Primary Outcome: Proportion of Subjects Achieving ≥5% Weight Loss*  

SEQUEL: Secondary Outcomes and Adverse Events  

Last Modified: 3/23/2015