QSYMIA® (PHENTERMINE + TOPIRAMATE)





Acronyms



MECHANISM OF ACTION



FDA-APPROVED INDICATIONS



WEIGHT LOSS


RCT
CONQUER trial - Qsymia® vs Placebo for Weight Loss in Obese Patients, Lancet (2011) [PubMed abstract]
  • The CONQUER trial enrolled 2487 overweight and obese patients with risk factors for heart disease
Main inclusion criteria
  • BMI 27 - 45
  • Two or more of the following: SBP 140-160, DBP 90-100 or taking ≥ 2 blood pressure medications, triglycerides 200-400 mg/dl or taking ≥ 2 lipid lowering drugs, fasting blood sugar > 100 mg/dl or 2-hour glucose load > 140 mg/dl or type 2 diabetes managed with lifestyle or metformin monotherapy
  • Waist circumference ≥ 42 inches for men and 34.6 inches for women
Main exclusion criteria
  • Blood pressure > 160/100
  • Fasting blood sugar > 240 mg/dl
  • Triglycerides > 400 mg/dl
  • Type 1 diabetes
  • Taking diabetes drug other than metformin
  • History of kidney stones
  • Significant depression
  • Taking tricyclic antidepressant or MAO inhibitor
Baseline characteristics
  • Average age 51 years
  • Average BMI - 36
  • Average weight - 227 lbs (103 kg)
  • Female sex - 70%
  • Average blood pressure - 128/80
  • Diabetes or prediabetes - 68%
Randomized treatment groups
  • Group 1 (994 patients) - Placebo once daily for 56 weeks
  • Group 2 (498 patients) - Phentermine CR 7.5 mg + Topiramate 46 mg once daily (Qsymia®) for 56 weeks
  • Group 3 (995 patients) - Phentermine CR 15 mg + Topiramate 92 mg once daily (Qsymia®) for 56 weeks
  • All patients were given diet counseling with instructions to decrease their caloric intake by 500 calories/day
Primary outcome: Coprimary outcomes were the average percentage change in body weight and the proportion of patients achieving at least 5% weight loss
Results

Duration: 56 weeks
Outcome Placebo Qsy 7.5/46 Qsy 15/92 Comparisons
Primary outcome (% weight loss) 1.2% 7.8% 9.8% 2 or 3 vs 1 p<0.0001
Primary outcome (≥ 5% weight loss) 21% 62% 70% 2 or 3 vs 1 p<0.0001
Weight loss at 1 year 3 lbs 17.82 lbs 22.4 lbs N/A
Dropout rate 43% 31% 36% N/A
Dry mouth 2% 13% 21% 2 or 3 vs 1 p<0.0001
Paresthesia 2% 14% 21% 2 or 3 vs 1 p<0.0001
Taste perversion 1% 7% 10% 2 or 3 vs 1 p<0.0001
Insomnia 5% 6% 10% 3 vs 1 p<0.0001
Dizziness 3% 7% 10% 2 or 3 vs 1 p<0.05
Disturbance in attention <1% 2% 4% 2 or 3 vs 1 p<0.05
  • Blood pressure decreased in all 3 groups over the course of the study. The decrease in the Qsymia groups was significantly greater than the placebo group.

Findings: 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.

RCT
SEQUEL trial - One-year Extension of the CONQUER Trial, The American Journal of Clinical Nutrition (2012) [PubMed abstract]
  • The SEQUEL trial enrolled 676 participants who completed the CONQUER trial and volunteered to continue their assigned treatment for another year
Results

Duration: Total of 108 weeks (including CONQUER)
Outcome Placebo
(N=227)
Qsy 7.5/46
(N=153)
Qsy 15/92
(N=295)
Comparisons
Primary outcome (% weight loss) 1.8% 9.3% 10.5% 2 or 3 vs 1 p<0.0001
Primary outcome (≥ 5% weight loss) 30% 75.2% 79.3% 2 or 3 vs 1 p<0.0001
  • Both systolic and diastolic blood pressure decreased by 3 - 5 mm Hg at 108 weeks compared with baseline in all treatment arms
  • Average heart rate increased by 0.4 bpm in placebo subjects, 1.3 bpm in 7.5/46 subjects, and 1.7 bpm in 15/92 subjects
  • The mean changes in bicarbonate from baseline to week 108 were +2.2, +0.7, and +0.2 mEq/L for placebo, 7.5/46, and 15/92, respectively. More Qsymia-treated subjects had a decrease from baseline in serum bicarbonate of > 5 mEq/L at two consecutive visits over the 108 study (placebo - 1.8%, 7.5/46 mg - 13.1%, 15/92 - 16.3%)

Findings: Qsymia in conjunction with lifestyle modification may provide a well-tolerated and effective option for the sustained treatment of obesity complicated by cardiometabolic disease.

RCT
Qsymia vs Placebo for Weight Loss in Obese Adolescents, NEJM Evidence (2022) [NEJM abstract]
  • The trial enrolled 223 obese adolescents aged 12 - 17 years
Main inclusion criteria
  • Age 12 - 17 years
  • BMI ≥ 95th percentile
Main exclusion criteria
  • Stimulant use
  • Congenital heart disease
  • Elevated blood pressure
  • History of bipolar or depression
Baseline characteristics
  • Average age 14 years
  • Female - 54%
  • Average weight - 233 lbs (106 kg)
  • Average BMI - 37.8
Randomized treatment groups
  • Group 1 (56 patients): Placebo
  • Group 2 (54 patients): Qsymia 7.5/46 mg once daily
  • Group 3 (113 patients): Qsymia 15/92 mg once daily
  • All participants were instructed to follow a 500-kilocalorie/day deficit diet plan and lifestyle modifications
Primary outcome: Mean percent change in BMI from randomization to week 56
Results

Duration: 56 weeks
Outcome Placebo Qsy 7.5/46 Qsy 15/92 Comparisons
% BMI change +3.3% -4.8% -7.1% p<0.001 for both doses
Weight change +14.5 lbs (6.57 kg) -12 lbs (5.5 kg) -20 lbs (9.2 kg) p<0.05 for both doses
Psychiatric disorders 1.8% 7.4% 8.8% N/A
Dropouts 43% 24% 35% N/A
  • Besides psychiatric disorders, side effects were similar between groups, and adverse events leading to discontinuation were rare (< 2%)
  • There was no significant difference between groups in SBP and heart rate changes from baseline
  • The authors attribute much of the high dropout rate to the fact that the study took place during the height of the COVID-19 pandemic

Findings: Phentermine/topiramate at both the mid and top doses offered a statistically significant reduction in BMI and favorably impacted triglyceride and HDL-C levels in adolescents with obesity.



SIDE EFFECTS


  • Reference [4]
Side effect Qsymia 15/92 mg Placebo
Paresthesia 20% 2%
Dry mouth 19% 3%
Constipation 16% 6%
Upper respiratory infection 14% 13%
Headache 11% 9%
Taste perversion 9% 1%
Insomnia 9% 5%
Nasopharyngitis 9% 8%
Dizziness 9% 3%
















CONTRAINDICATIONS



PRECAUTIONS








DRUG INTERACTIONS



DOSING





STUDIES




LONG-TERM SAFETY



BIBLIOGRAPHY