Phentermine with topiramate (Qsymia) is a combination capsule for weight management. Its evidence is placebo-controlled trials lasting 56 to 108 weeks, mostly in adults with several risk factors. This article covers the weight trials, the blood sugar and blood pressure findings, the side effects and the pregnancy rule.
Weight: CONQUER
CONQUER randomized 2,487 adults with overweight or obesity and at least two risk factors to placebo or to one of two doses of controlled-release phentermine with topiramate, for 56 weeks. The mean change was -1.2% on placebo, -7.8% on the low dose (phentermine 7.5 mg with topiramate 46 mg) and -9.8% on the high dose (15 mg with 92 mg). In kilograms that was -1.4, -8.1 and -10.2 kg (CONQUER, Lancet 2011). At least 5% weight loss was reached by 21%, 62% and 70% of the three groups.
A second trial: EQUIP
EQUIP randomized adults with a BMI of 35 or higher to placebo, a low dose (3.75 mg with 23 mg) or the high dose (15 mg with 92 mg) for 56 weeks, alongside a reduced-calorie diet. Weight fell 1.6%, 5.1% and 10.9% of baseline body weight. Compared with placebo, the high dose also improved waist circumference, blood pressure, fasting glucose and lipids (EQUIP, Obesity 2012).
Blood sugar over two years
In a 108-week subanalysis of people with prediabetes or metabolic syndrome at the start, mean weight loss was 2.5% on placebo, 10.9% on the low dose and 12.1% on the high dose. Progression to type 2 diabetes was 70.5% lower on the low dose and 78.7% lower on the high dose, a pattern that tracked the weight lost (Diabetes Care 2014). This was a subgroup analysis, not a trial designed to prevent diabetes.
Side effects and the pregnancy rule
- Dry mouth, tingling (paresthesia), constipation, insomnia and taste change were the most common effects. In CONQUER, dry mouth affected 21% on the high dose and 2% on placebo (CONQUER, Lancet 2011).
- The label contraindicates use in pregnancy, glaucoma, hyperthyroidism, and with an MAO inhibitor taken within 14 days (Qsymia prescribing information, DailyMed).
- Qsymia is dispensed under a Risk Evaluation and Mitigation Strategy (REMS) because topiramate can cause fetal harm (Qsymia prescribing information, DailyMed).
What this does not say
- The trial averages are for the controlled-release capsule at the studied doses, in trial settings. They are not predictions for one person.
- Compounded combinations of phentermine and topiramate were not studied; the trials used the manufactured capsule.
- The 108-week figures come from a prediabetes and metabolic syndrome subgroup, and the trials were sponsored by the manufacturer.
How we use this
Our physicians consider this combination for people with obesity and several risk factors, with a pregnancy plan in place, and reassess weight and blood pressure at set intervals.
If you may become pregnant, the label rules this combination out. Say so at your consultation.
Explore weight loss treatmentsSources
- 1.Gadde KM et al. Effects of low-dose, controlled-release phentermine plus topiramate on weight and comorbidities (CONQUER). Lancet 2011. The Lancet
- 2.Allison DB et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity 2012. Obesity
- 3.Prevention of type 2 diabetes in subjects with prediabetes and metabolic syndrome treated with phentermine and topiramate extended release. Diabetes Care 2014. Diabetes Care
- 4.Qsymia (phentermine and topiramate) extended-release capsules, prescribing information. DailyMed